<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article
  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="3.0" xml:lang="en">
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group>
<journal-title>PLoS ONE</journal-title></journal-title-group>
<issn pub-type="epub">1932-6203</issn>
<publisher>
<publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc></publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">PONE-D-14-12620</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0099912</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology and life sciences</subject><subj-group><subject>Psychology</subject><subj-group><subject>Addiction</subject><subj-group><subject>Substance addiction</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine and health sciences</subject><subj-group><subject>Mental health and psychiatry</subject><subj-group><subject>Substance-related disorders</subject></subj-group></subj-group><subj-group><subject>Public and occupational health</subject></subj-group></subj-group></article-categories>
<title-group>
<article-title>Effectiveness of Guided and Unguided Low-Intensity Internet Interventions for Adult Alcohol Misuse: A Meta-Analysis</article-title>
<alt-title alt-title-type="running-head">Internet Interventions for Adult Alcohol Misuse: A Meta-Analysis</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Riper</surname><given-names>Heleen</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Blankers</surname><given-names>Matthijs</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Hadiwijaya</surname><given-names>Hana</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff11"><sup>11</sup></xref></contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Cunningham</surname><given-names>John</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref><xref ref-type="aff" rid="aff7"><sup>7</sup></xref></contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Clarke</surname><given-names>Stella</given-names></name><xref ref-type="aff" rid="aff8"><sup>8</sup></xref></contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Wiers</surname><given-names>Reinout</given-names></name><xref ref-type="aff" rid="aff9"><sup>9</sup></xref></contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ebert</surname><given-names>David</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff10"><sup>10</sup></xref></contrib>
<contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Cuijpers</surname><given-names>Pim</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib>
</contrib-group>
<aff id="aff1"><label>1</label><addr-line>Department of Clinical Psychology and EMGO Institute, VU University Amsterdam, Amsterdam, Netherlands</addr-line></aff>
<aff id="aff2"><label>2</label><addr-line>Division Health Trainings online, EU innovation Incubator, Leuphana University, Lüneburg, Germany</addr-line></aff>
<aff id="aff3"><label>3</label><addr-line>Arkin Mental Health Care, Amsterdam, the Netherlands</addr-line></aff>
<aff id="aff4"><label>4</label><addr-line>Trimbos Institute, Netherlands Institute of Mental Health and Addiction, Utrecht, The Netherlands</addr-line></aff>
<aff id="aff5"><label>5</label><addr-line>Amsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Centre, University of Amsterdam, the Netherlands</addr-line></aff>
<aff id="aff6"><label>6</label><addr-line>Centre for Mental Health Research, the Australian National University, Canberra, Australia</addr-line></aff>
<aff id="aff7"><label>7</label><addr-line>Centre for Addiction and Mental Health, Toronto, Canada</addr-line></aff>
<aff id="aff8"><label>8</label><addr-line>NHS Fife, Edinburgh, Scotland, United Kingdom</addr-line></aff>
<aff id="aff9"><label>9</label><addr-line>Addiction, Development and Psychopathology (ADAPT) lab, Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands</addr-line></aff>
<aff id="aff10"><label>10</label><addr-line>Division for Clinical Psychology and Psychotherapy, Department for Psychology, Philipp’s University Marburg, Marburg, Germany</addr-line></aff>
<aff id="aff11"><label>11</label><addr-line>TS Social and Behavioral Sciences, Department of Developmental Psychology, Tilburg University, Tilburg, the Netherlands</addr-line></aff>
<contrib-group>
<contrib contrib-type="editor" xlink:type="simple"><name name-style="western"><surname>Stewart</surname><given-names>Robert</given-names></name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"/></contrib>
</contrib-group>
<aff id="edit1"><addr-line>Institute of Psychiatry, United Kingdom</addr-line></aff>
<author-notes>
<corresp id="cor1">* E-mail: <email xlink:type="simple">h.riper@vu.nl</email></corresp>
<fn fn-type="conflict"><p>The authors have declared that no competing interests exist.</p></fn>
<fn fn-type="con"><p>Conceived and designed the experiments: HR HH PC. Performed the experiments: HR HH MB. Analyzed the data: HR HH MB PC. Contributed reagents/materials/analysis tools: HR PC. Contributed to the writing of the manuscript: HR MB HH JC SC DE RW PC.</p></fn>
</author-notes>
<pub-date pub-type="collection"><year>2014</year></pub-date>
<pub-date pub-type="epub"><day>17</day><month>6</month><year>2014</year></pub-date>
<volume>9</volume>
<issue>6</issue>
<elocation-id>e99912</elocation-id>
<history>
<date date-type="received"><day>20</day><month>3</month><year>2014</year></date>
<date date-type="accepted"><day>19</day><month>5</month><year>2014</year></date>
</history>
<permissions>
<copyright-year>2014</copyright-year>
<copyright-holder>Riper et al</copyright-holder><license xlink:type="simple"><license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/" xlink:type="simple">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions>
<abstract><sec>
<title>Background</title>
<p>Alcohol misuse ranks within the top ten health conditions with the highest global burden of disease. Low-intensity, Internet interventions for curbing adult alcohol misuse have been shown effective. Few meta-analyses have been carried out, however, and they have involved small numbers of studies, lacked indicators of drinking within low risk guidelines, and examined the effectiveness of <italic>unguided</italic> self-help only. We therefore conducted a more thorough meta-analysis that included both <italic>guided</italic> and <italic>unguided</italic> interventions.</p>
</sec><sec>
<title>Methods</title>
<p>Systematic literature searches were performed up to September 2013. Primary outcome was the mean level of alcohol consumption and drinking within low risk guidelines for alcohol consumption at post-treatment.</p>
</sec><sec>
<title>Findings</title>
<p>We selected 16 randomised controlled trials (with 23 comparisons and 5,612 participants) for inclusion. Results, showed a small but significant overall effect size in favour of Internet interventions (<italic>g</italic> = 0.20, 95% CI: 0.13–0.27, <italic>p</italic>&lt;.001). Participants in Internet interventions drunk on average 22 grams of ethanol less than controls and were significantly more likely to be adhering to low-risk drinking guidelines at post-treatment (RD 0.13, 95% CI: 0.09–0.17, <italic>p</italic>&lt;.001). Subgroup analyses revealed no significant differences in potential moderators for the outcome of alcohol consumption, although there was a near-significant difference between comparisons with waitlist control and those with assessment-only or alcohol information control conditions (<italic>p</italic> = .056).</p>
</sec><sec>
<title>Conclusions</title>
<p>Internet interventions are effective in reducing adult alcohol consumption and inducing alcohol users to adhere to guidelines for low-risk drinking. This effect is small but from a public health point of view this may warrant large scale implementation at low cost of Internet interventions for adult alcohol misuse. Moderator analyses with sufficient power are, however, needed in order to assess the robustness of these overall results and to assess whether these interventions may impact on subgroups with different levels of success.</p>
</sec></abstract>
<funding-group><funding-statement>The authors have no support or funding to report.</funding-statement></funding-group><counts><page-count count="11"/></counts><custom-meta-group><custom-meta id="data-availability" xlink:type="simple"><meta-name>Data Availability</meta-name><meta-value>The authors confirm that all data underlying the findings are fully available without restriction. All data are included within the paper.</meta-value></custom-meta></custom-meta-group></article-meta>
</front>
<body><sec id="s1">
<title>Introduction</title>
<p>The <italic>Global Burden of Disease Study 2010</italic> from the World Health Organization has documented a growing health burden from Alcohol Use Disorders (AUDs) over the past two decades among adults in both developed and developing societies <xref ref-type="bibr" rid="pone.0099912-Whiteford1">[1]</xref>, <xref ref-type="bibr" rid="pone.0099912-Tang1">[2]</xref>. The health burden increases further if the whole spectrum of alcohol misuse <xref ref-type="bibr" rid="pone.0099912-Moyer1">[3]</xref> is taken into account, whereby people consume alcohol in excess of the low-risk drinking guidelines but do not meet AUD criteria <xref ref-type="bibr" rid="pone.0099912-Whiteford1">[1]</xref>, <xref ref-type="bibr" rid="pone.0099912-Saunders1">[4]</xref>, <xref ref-type="bibr" rid="pone.0099912-WHO1">[5]</xref>. They include people who engage in <italic>hazardous alcohol use</italic> – and who may thereby develop physical, psychological and social problems in the short term and alcohol dependency and serious or fatal illness later on – or <italic>harmful alcohol use</italic>, meaning that they are already experiencing such problems <xref ref-type="bibr" rid="pone.0099912-Saunders1">[4]</xref>. This mounting health burden is due not just to population growth or ageing, but also to an absolute increase in alcohol consumption by adults <xref ref-type="bibr" rid="pone.0099912-Whiteford1">[1]</xref>, <xref ref-type="bibr" rid="pone.0099912-Degenhardt1">[6]</xref>. It affects both traditional groups of drinkers and newer groups such as women <xref ref-type="bibr" rid="pone.0099912-Grucza1">[7]</xref> and the elderly <xref ref-type="bibr" rid="pone.0099912-Watson1">[8]</xref>. The risks of problem drinking multiply with every increment in alcohol consumption or every heavier drinking pattern <xref ref-type="bibr" rid="pone.0099912-Parry1">[9]</xref>, <xref ref-type="bibr" rid="pone.0099912-Rehm1">[10]</xref>. Estimates reveal that eight out of ten adults who drink too much alcohol lack professional help; if they do receive it, that is often at a very late stage in their drinking career <xref ref-type="bibr" rid="pone.0099912-Cunningham1">[11]</xref>. Studies also show that whilst a high number of people who misuse alcohol do desire help, they prefer it outside conventional health care settings <xref ref-type="bibr" rid="pone.0099912-KoskiJanne1">[12]</xref>. Public health strategies to curb alcohol misuse therefore have considerable room for improvement. One particular enhancement could lie in an expanded availability of brief, low-intensity Internet interventions for use both in and beyond the primary care sector <xref ref-type="bibr" rid="pone.0099912-Nilsen1">[13]</xref>, <xref ref-type="bibr" rid="pone.0099912-Wilson1">[14]</xref>.</p>
<p>Conventional (that is, non-Internet) Screening and Brief Interventions (SBIs) have been evaluated mostly in their delivery to non–alcohol-dependent, non–treatment-seeking adults whose alcohol misuse was identified in opportunistic health screening in primary care. Numerous meta-analyses and systematic reviews have convincingly shown the clinical effectiveness of SBIs in reducing alcohol consumption in comparison to non-intervention controls. The results of all these studies have recently been synthesised in studies by Jonas and colleagues <xref ref-type="bibr" rid="pone.0099912-Jonas1">[15]</xref>, <xref ref-type="bibr" rid="pone.0099912-Jonas2">[16]</xref>, and these in turn by Moyer in her 2013 update to the United States Preventive Services Task Force’s earlier recommendation statement on screening and brief interventions in primary care for alcohol misuse <xref ref-type="bibr" rid="pone.0099912-Moyer1">[3]</xref>. Overall, the results show significant effect sizes in the small to moderate range for low-intensity interventions in comparison to control conditions in terms of average decreases in alcohol consumption <xref ref-type="bibr" rid="pone.0099912-Moyer1">[3]</xref>, <xref ref-type="bibr" rid="pone.0099912-Jonas1">[15]</xref>, <xref ref-type="bibr" rid="pone.0099912-Jonas2">[16]</xref>. Cost-effectiveness studies, albeit limited in number, also report promising results <xref ref-type="bibr" rid="pone.0099912-Latimer1">[17]</xref>–<xref ref-type="bibr" rid="pone.0099912-Tariq1">[19]</xref>. Effectiveness studies on the reduction of alcohol consumption through SBIs provided in other settings such as general hospitals, emergency departments or work environments have been inconclusive <xref ref-type="bibr" rid="pone.0099912-Mdege1">[20]</xref>–<xref ref-type="bibr" rid="pone.0099912-Osilla1">[23]</xref>.</p>
<p>Providing Internet self-help interventions both in primary care and directly to people in the community appears a promising strategy to overcome the gap between the high number of people that misuse alcohol and the low number that actually receive or seek help in primary care <xref ref-type="bibr" rid="pone.0099912-Hester1">[24]</xref>. Studies on web-based self-help interventions for adult problem drinking show that (1) the interventions are mostly of an unguided nature and are delivered as stand-alone procedures directly to participants in the community, and to a far lesser extent via primary care, clinical or employment settings <xref ref-type="bibr" rid="pone.0099912-White1">[25]</xref>, <xref ref-type="bibr" rid="pone.0099912-Riper1">[26]</xref>; (2) they largely reach first-time help seekers (with rates varying from 80% to 90% <xref ref-type="bibr" rid="pone.0099912-Cunningham2">[27]</xref>, <xref ref-type="bibr" rid="pone.0099912-Riper2">[28]</xref>); (3) people who misuse alcohol take up these services on a much wider scale than the available brief, low-intensity face-to-face interventions in primary care settings <xref ref-type="bibr" rid="pone.0099912-Hester1">[24]</xref>, <xref ref-type="bibr" rid="pone.0099912-Vernon1">[29]</xref>; and (4) people differ in whether they desire additional help from professionals <xref ref-type="bibr" rid="pone.0099912-Riper2">[28]</xref>. Studies have also shown such unguided interventions to be effective in reducing adult alcohol misuse as compared to no-intervention control conditions. A 2011 meta-analysis by Riper and colleagues <xref ref-type="bibr" rid="pone.0099912-Riper1">[26]</xref> found a small but significant effect size of <italic>g</italic> = 0.39 (95% CI: 0.23–0.56) for unguided self-help interventions via the Internet. Numbers needed to treat (NNT = 5) were comparable to those for face-to-face brief interventions in primary care settings <xref ref-type="bibr" rid="pone.0099912-Kaner1">[30]</xref>. Small effect sizes also emerged in meta-analyses on various health promotion interventions, including alcohol use <xref ref-type="bibr" rid="pone.0099912-Rooke1">[31]</xref>, <xref ref-type="bibr" rid="pone.0099912-Portnoy1">[32]</xref>. Few cost-effectiveness studies are available, but they indicate potential economic gain from Internet-based interventions for adult alcohol misuse <xref ref-type="bibr" rid="pone.0099912-Blankers1">[33]</xref>.</p>
<p>The number of eligible randomised controlled trials on web-based interventions for alcohol misuse was rather limited in these systematic reviews and meta-analyses. The Riper meta-analysis <xref ref-type="bibr" rid="pone.0099912-Riper1">[26]</xref>, for example, identified only 7 eligible randomised controlled trials. This sharply contrasts with meta-analyses assessing the clinical and cost-effectiveness of Internet interventions for depression or anxiety. For example, Richards and Richardson <xref ref-type="bibr" rid="pone.0099912-Richards1">[34]</xref> were able to include 19 RCTs on depression in their 2012 meta-analysis. For these disorders, overall evidence is accumulating that guided interventions generally lead to a greater reduction of depressive or anxiety symptoms than unguided interventions <xref ref-type="bibr" rid="pone.0099912-Richards1">[34]</xref>, <xref ref-type="bibr" rid="pone.0099912-Cuijpers1">[35]</xref> and that guided Internet interventions are as effective as face to face interventions <xref ref-type="bibr" rid="pone.0099912-Cuijpers2">[36]</xref>.</p>
<p>Recently, the numbers of published randomised controlled trials on Internet-based interventions for alcohol misuse has increased, including some that evaluate therapist-led self-help interventions <xref ref-type="bibr" rid="pone.0099912-Blankers2">[37]</xref>, <xref ref-type="bibr" rid="pone.0099912-Postel1">[38]</xref>. We therefore decided to conduct this meta-analysis. We investigated the overall effectiveness of alcohol interventions in comparison to no-intervention controls and, if possible in terms of alcohol consumption reduction, drinking within the guidelines for low risk drinking and actual amounts reduced. We then examined whether certain study characteristics, such as the guided or unguided design of interventions, affected the primary outcome measure of alcohol consumption. To the best of our knowledge, this is the first meta-analysis that includes both guided and unguided Internet interventions to address problematic alcohol consumption among adults.</p>
</sec><sec id="s2" sec-type="methods">
<title>Methods</title>
<sec id="s2a">
<title>Identification of Studies</title>
<p>We conducted literature searches up to September 2013 in the following bibliographic databases: MEDLINE, PsycINFO, Science Citation Index Expanded, Social Sciences Citation Index, Arts and Humanities Citation Index, CINAHL, PUBMED and EMBASE, using key words and text words. Words indicating online interventions (Internet, Web, online, computer, mobile) were combined with terms indicative of type of treatment (self-help, brief intervention, treatment, unguided, guided, supported, low-intensity) and problematic alcohol use (alcohol abuse, alcohol misuse, problem drinking, hazardous, harmful, dependence, abstinence). We also re-examined exclusion lists of papers retrieved for our previous meta-analysis <xref ref-type="bibr" rid="pone.0099912-Riper1">[26]</xref> to see if any would meet the inclusion criteria for the current study. No language restrictions were applied.</p>
<p>Our initial selection was based on titles and abstracts. If these yielded insufficient information to assess the eligibility criteria, full-text articles were retrieved and assessed in terms of our inclusion criteria. All papers included or excluded at all stages were assessed by two independent raters (authors HR and HH) (see <xref ref-type="fig" rid="pone-0099912-g001">figure 1</xref>). The same raters assessed the effect sizes and moderator variables in the included studies. Any disagreement was resolved by discussion. A protocol does not exist for this meta-analysis; steps undertaken are described in this method section.</p>
<fig id="pone-0099912-g001" position="float"><object-id pub-id-type="doi">10.1371/journal.pone.0099912.g001</object-id><label>Figure 1</label><caption>
<title>Study inclusion meta-analysis: flow chart.</title>
</caption><graphic mimetype="image" xlink:href="info:doi/10.1371/journal.pone.0099912.g001" position="float" xlink:type="simple"/></fig></sec><sec id="s2b">
<title>Eligibility Criteria</title>
<p>Randomised controlled trials were included that (1) compared a web-based intervention with a control group (in an assessment-only, waitlisted or alcohol information brochure control condition); (2) included a low-intensity self-help intervention that the participant could perform on a computer or mobile phone, with or without guidance from a professional; (3) assessed alcohol drinking behaviour in terms of quantity consumed as a primary outcome measure; (4) studied adults aged 18 or older; (5) included alcohol drinkers who exceeded local guidelines for low-risk drinking (if lower-risk participants were also included, we retained only the results of those with alcohol misuse).</p>
</sec><sec id="s2c">
<title>Risk-of-bias Assessment and Data Extraction</title>
<p>We assessed the validity of the included studies on the basis of four criteria from the risk-of-bias assessment tool developed by the Cochrane Collaboration <xref ref-type="bibr" rid="pone.0099912-Higgins1">[39]</xref>. It verifies study attributes in randomised controlled trials that are potential sources of bias, including (1) adequacy of allocation sequence generation, (2) concealment of the allocation to the different conditions, (3) blinding of assessors and outcomes and (4) handling of incomplete outcome data using intention-to-treat analyses (this was rated as positive if intention-to-treat analyses were performed, thus retaining all randomised participants in the analyses; see <xref ref-type="table" rid="pone-0099912-t001">table 1</xref>). Authors HH and MB assessed risk of bias as Yes, No or Unclear using the Cochrane Collaboration tool (see 2.3).</p>
<table-wrap id="pone-0099912-t001" position="float"><object-id pub-id-type="doi">10.1371/journal.pone.0099912.t001</object-id><label>Table 1</label><caption>
<title>Study characteristics of 16 randomised controlled trials of Internet-based interventions for adult alcohol misuse.</title>
</caption><alternatives><graphic id="pone-0099912-t001-1" position="float" mimetype="image" xlink:href="info:doi/10.1371/journal.pone.0099912.t001" xlink:type="simple"/>
<table><colgroup span="1"><col align="left" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/></colgroup>
<thead>
<tr>
<td align="left" rowspan="1" colspan="1">Author, year, country</td>
<td align="left" rowspan="1" colspan="1">Recruitment</td>
<td align="left" rowspan="1" colspan="1">Target group,inclusion criteria</td>
<td align="left" rowspan="1" colspan="1">Deliverymode |setting</td>
<td align="left" rowspan="1" colspan="1">Type of support |intervention(s) | dosage</td>
<td align="left" rowspan="1" colspan="1">Comparison (interventionvs control)</td>
<td align="left" rowspan="1" colspan="1">N<sup>a</sup>/N<sup>b</sup></td>
<td align="left" rowspan="1" colspan="1">Outcomemeasure</td>
<td align="left" rowspan="1" colspan="1">ITT or CO</td>
<td align="left" rowspan="1" colspan="1">Post-treat­mentassessment</td>
<td align="left" rowspan="1" colspan="1">DO</td>
<td align="left" rowspan="1" colspan="1">Risk of bias<sup>1–4</sup></td>
<td align="left" rowspan="1" colspan="1">Baseline: M (SD) drinks<sup>k</sup> per week | and/or AUDIT score</td>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="1" colspan="1">Araki, 2006, Japan</td>
<td align="left" rowspan="1" colspan="1">Workplace</td>
<td align="left" rowspan="1" colspan="1">Males, GGT ≥60 IU/I</td>
<td align="left" rowspan="1" colspan="1">E-mail | workplace</td>
<td align="left" rowspan="1" colspan="1">Guided |HE | 2 sessions</td>
<td align="left" rowspan="1" colspan="1">Guided vs AO</td>
<td align="left" rowspan="1" colspan="1">12/12</td>
<td align="left" rowspan="1" colspan="1">Drinks per day</td>
<td align="left" rowspan="1" colspan="1">CO</td>
<td align="left" rowspan="1" colspan="1">2 months</td>
<td align="left" rowspan="1" colspan="1">3%</td>
<td align="left" rowspan="1" colspan="1">1) Unclear* 2) No 3) Unclear* 4) No</td>
<td align="left" rowspan="1" colspan="1">Drinks: 18.6 (12.2) | AUDIT: -</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Bischof, 2008, Germany</td>
<td align="left" rowspan="1" colspan="1">General practice</td>
<td align="left" rowspan="1" colspan="1">GP patients age 18–64, alcohol dependence or abuse, or &gt;20/30 g of alcohol per day for females/males in past 4 weeks, or &gt;60/80 g for females/males on &gt;1 occasion in the past 4 weeks</td>
<td align="left" rowspan="1" colspan="1">E-mail, phone | home</td>
<td align="left" rowspan="1" colspan="1">Guided |BCC, MI, TTM | 4 sessions (FC) or max. 3 sessions (SC)</td>
<td align="left" rowspan="1" colspan="1">1) Guided SC<sup>c</sup> vs AB/H; 2) Guided FC<sup>d</sup> vs AB/H</td>
<td align="left" rowspan="1" colspan="1">1) 131/139∧; 2) 138/139∧</td>
<td align="left" rowspan="1" colspan="1">Grams of alcohol per day</td>
<td align="left" rowspan="1" colspan="1">ITT</td>
<td align="left" rowspan="1" colspan="1">12 months</td>
<td align="left" rowspan="1" colspan="1">8%</td>
<td align="left" rowspan="1" colspan="1">1) Yes 2) No 3) Yes 4) Yes</td>
<td align="left" rowspan="1" colspan="1">Drinks: 31.9 (35.2) | AUDIT: -</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Blankers, 2011, Netherlands</td>
<td align="left" rowspan="1" colspan="1">Community</td>
<td align="left" rowspan="1" colspan="1">Males/females, AUDIT≥8 and ≥14 units/week</td>
<td align="left" rowspan="1" colspan="1">Internet | home</td>
<td align="left" rowspan="1" colspan="1">Guided and unguided |CBT, MI | 7 sessions guided, 6 modules unguided</td>
<td align="left" rowspan="1" colspan="1">1) Guided vs WL; 2) Unguided vs WL</td>
<td align="left" rowspan="1" colspan="1">1) 68/69∧; 2) 68/69∧</td>
<td align="left" rowspan="1" colspan="1">Drinks in past week</td>
<td align="left" rowspan="1" colspan="1">ITT</td>
<td align="left" rowspan="1" colspan="1">3 months; 6 months</td>
<td align="left" rowspan="1" colspan="1">30%</td>
<td align="left" rowspan="1" colspan="1">1) Yes 2) No 3) Yes 4) Yes</td>
<td align="left" rowspan="1" colspan="1">Drinks: 44.7 (26.4) | AUDIT: 19.5 (5.1)</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Boon &amp; Huiberts, 2006, Netherlands</td>
<td align="left" rowspan="1" colspan="1">Community</td>
<td align="left" rowspan="1" colspan="1">Males/females, ≥21/14 units/week; or ≥6/4 units on ≥1 day/week</td>
<td align="left" rowspan="1" colspan="1">Internet | research setting</td>
<td align="left" rowspan="1" colspan="1">Unguided |PNF | single-session</td>
<td align="left" rowspan="1" colspan="1">Unguided vs AB</td>
<td align="left" rowspan="1" colspan="1">102/89</td>
<td align="left" rowspan="1" colspan="1">Drinks per week</td>
<td align="left" rowspan="1" colspan="1">CO</td>
<td align="left" rowspan="1" colspan="1">9 months</td>
<td align="left" rowspan="1" colspan="1">32%</td>
<td align="left" rowspan="1" colspan="1">1) Yes 2) No 3) Yes 4) No</td>
<td align="left" rowspan="1" colspan="1">Drinks: <bold>-</bold> | AUDIT: -</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Boon, 2011, Netherlands</td>
<td align="left" rowspan="1" colspan="1">Community</td>
<td align="left" rowspan="1" colspan="1">Males, ≥21 units/week or ≥6 units ≥1 day per week</td>
<td align="left" rowspan="1" colspan="1">Internet | research setting</td>
<td align="left" rowspan="1" colspan="1">Unguided |PNF | single-session</td>
<td align="left" rowspan="1" colspan="1">Unguided vs AB</td>
<td align="left" rowspan="1" colspan="1">230/220</td>
<td align="left" rowspan="1" colspan="1">Drinks per week</td>
<td align="left" rowspan="1" colspan="1">ITT</td>
<td align="left" rowspan="1" colspan="1">1 month; 6 months</td>
<td align="left" rowspan="1" colspan="1">8%</td>
<td align="left" rowspan="1" colspan="1">1) Yes 2) Yes 3) Yes 4) Yes</td>
<td align="left" rowspan="1" colspan="1">Drinks: 31.3 (16.8) | AUDIT: -</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Brendryen, 2013, Norway</td>
<td align="left" rowspan="1" colspan="1">Community</td>
<td align="left" rowspan="1" colspan="1">FAST ≥3</td>
<td align="left" rowspan="1" colspan="1">Internet | home</td>
<td align="left" rowspan="1" colspan="1">Unguided | PNF, CBT | multiple sessions</td>
<td align="left" rowspan="1" colspan="1">Unguided vs AB</td>
<td align="left" rowspan="1" colspan="1">125/119</td>
<td align="left" rowspan="1" colspan="1">Drinks per week</td>
<td align="left" rowspan="1" colspan="1">ITT</td>
<td align="left" rowspan="1" colspan="1">2 months; 6 months*</td>
<td align="left" rowspan="1" colspan="1">37%</td>
<td align="left" rowspan="1" colspan="1">1) Yes 2) Yes 3) Yes 4) Yes</td>
<td align="left" rowspan="1" colspan="1">Drinks: 23.5 (16.1) | AUDIT: -</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Cunningham, 2009, Canada</td>
<td align="left" rowspan="1" colspan="1">Community</td>
<td align="left" rowspan="1" colspan="1">Males/females, AUDIT ≥11</td>
<td align="left" rowspan="1" colspan="1">Internet | home</td>
<td align="left" rowspan="1" colspan="1">Unguided |PNF | single-session</td>
<td align="left" rowspan="1" colspan="1">Unguided vs AB</td>
<td align="left" rowspan="1" colspan="1">35/37</td>
<td align="left" rowspan="1" colspan="1">Drinks per week</td>
<td align="left" rowspan="1" colspan="1">ITT</td>
<td align="left" rowspan="1" colspan="1">3 months; 6 months</td>
<td align="left" rowspan="1" colspan="1">8%</td>
<td align="left" rowspan="1" colspan="1">1) Yes 2) No 3) Yes 4) Yes</td>
<td align="left" rowspan="1" colspan="1">Drinks: 22.5 (12.6) | AUDIT-C: 8.9-</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Delrahim-Howlett, 2011, USA</td>
<td align="left" rowspan="1" colspan="1">Women’s and infant services</td>
<td align="left" rowspan="1" colspan="1">Females, ≥3 units on ≥1 day/month</td>
<td align="left" rowspan="1" colspan="1">Internet | health care</td>
<td align="left" rowspan="1" colspan="1">Unguided |PNF | single-session</td>
<td align="left" rowspan="1" colspan="1">Unguided vs ABdouble-blind</td>
<td align="left" rowspan="1" colspan="1">68/67</td>
<td align="left" rowspan="1" colspan="1">Drinks per occasion</td>
<td align="left" rowspan="1" colspan="1">CO</td>
<td align="left" rowspan="1" colspan="1">1 month; 2 months</td>
<td align="left" rowspan="1" colspan="1">10%</td>
<td align="left" rowspan="1" colspan="1">1) Yes 2) Yes 3) Yes 4) No</td>
<td align="left" rowspan="1" colspan="1">Drinks: 8.2 (7.5) | AUDIT: -</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Doumas &amp; Hannah, 2008, USA</td>
<td align="left" rowspan="1" colspan="1">Workplace</td>
<td align="left" rowspan="1" colspan="1">Males/females<sup>&amp;</sup>, ≥1 occasions with ≥5/4 units/past 2 weeks</td>
<td align="left" rowspan="1" colspan="1">Internet | workplace</td>
<td align="left" rowspan="1" colspan="1">Guided and unguided |PNF, MI | single-session</td>
<td align="left" rowspan="1" colspan="1">1) Guided vs AO 2) Unguided vs AO</td>
<td align="left" rowspan="1" colspan="1">1)12/16; 2) 8/7<sup> l</sup></td>
<td align="left" rowspan="1" colspan="1">Drinks per week</td>
<td align="left" rowspan="1" colspan="1">CO</td>
<td align="left" rowspan="1" colspan="1">1 month</td>
<td align="left" rowspan="1" colspan="1">37%</td>
<td align="left" rowspan="1" colspan="1">1) Yes 2) No 3) Yes 4) No</td>
<td align="left" rowspan="1" colspan="1">Drinks: 3.89 (2.44) | AUDIT: -</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Hansen, 2012, Denmark</td>
<td align="left" rowspan="1" colspan="1">Community</td>
<td align="left" rowspan="1" colspan="1">Males/females, ≥21/14 units/week</td>
<td align="left" rowspan="1" colspan="1">Internet | home</td>
<td align="left" rowspan="1" colspan="1">Unguided |PNF | single-session</td>
<td align="left" rowspan="1" colspan="1">1) Unguided advice vs AO 2) Unguided PF<sup>f</sup> vs AO</td>
<td align="left" rowspan="1" colspan="1">1) 476/454; 2) 450/454</td>
<td align="left" rowspan="1" colspan="1">Drinks per week</td>
<td align="left" rowspan="1" colspan="1">ITT</td>
<td align="left" rowspan="1" colspan="1">6 months; 12 months</td>
<td align="left" rowspan="1" colspan="1">37%</td>
<td align="left" rowspan="1" colspan="1">1) Yes 2) No 3) Yes 4) Yes</td>
<td align="left" rowspan="1" colspan="1">Drinks: 32.8 (13.5) | AUDIT: -</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Hester, 2005, USA</td>
<td align="left" rowspan="1" colspan="1">Community</td>
<td align="left" rowspan="1" colspan="1">Males/females, AUDIT ≥8</td>
<td align="left" rowspan="1" colspan="1">CD-ROM | health care</td>
<td align="left" rowspan="1" colspan="1">Unguided |PNF, BSC, MI |single-session extended</td>
<td align="left" rowspan="1" colspan="1">Unguided vs WL</td>
<td align="left" rowspan="1" colspan="1">35/26</td>
<td align="left" rowspan="1" colspan="1">Drinks per day</td>
<td align="left" rowspan="1" colspan="1">CO</td>
<td align="left" rowspan="1" colspan="1">4 weeks</td>
<td align="left" rowspan="1" colspan="1">0%</td>
<td align="left" rowspan="1" colspan="1">1) Yes 2) No 3) Yes 4) No</td>
<td align="left" rowspan="1" colspan="1">Drinks: 47.6 (42.9) | AUDIT: 19.7 (-)</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Pemberton<sup>m</sup>, 2011, USA</td>
<td align="left" rowspan="1" colspan="1">Military</td>
<td align="left" rowspan="1" colspan="1">Males/females<sup>&amp;</sup>,/all interested (we assessed high-risk group only)</td>
<td align="left" rowspan="1" colspan="1">Internet | home</td>
<td align="left" rowspan="1" colspan="1">Unguided |HBM, MI, SCM | 3 modules</td>
<td align="left" rowspan="1" colspan="1">1) Unguided combined vs AO; 2) Unguided MI<sup>h</sup> vs AO</td>
<td align="left" rowspan="1" colspan="1">1) 144/72; 2) 95/73<sup> l</sup></td>
<td align="left" rowspan="1" colspan="1">Drinks per occasion</td>
<td align="left" rowspan="1" colspan="1">ITT</td>
<td align="left" rowspan="1" colspan="1">1 month</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">1) No 2) NA* 3) Yes 4) Yes</td>
<td align="left" rowspan="1" colspan="1">Drinks: - | AUDIT: -</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Riper, 2007, Netherlands</td>
<td align="left" rowspan="1" colspan="1">Community</td>
<td align="left" rowspan="1" colspan="1">Males/females, &gt;21/14 units/week; or ≥6/4 units ≥1 day for past 3 months</td>
<td align="left" rowspan="1" colspan="1">Internet | home</td>
<td align="left" rowspan="1" colspan="1">Unguided |BSC, CBT, MI |6 weeks</td>
<td align="left" rowspan="1" colspan="1">Unguided vs AB</td>
<td align="left" rowspan="1" colspan="1">130/131</td>
<td align="left" rowspan="1" colspan="1">Drinks per week</td>
<td align="left" rowspan="1" colspan="1">ITT</td>
<td align="left" rowspan="1" colspan="1">6 months</td>
<td align="left" rowspan="1" colspan="1">42%</td>
<td align="left" rowspan="1" colspan="1">1) Yes 2) No 3) Yes 4) Yes</td>
<td align="left" rowspan="1" colspan="1">Drinks: 43.6 (21.7) | AUDIT: -</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Schulz, 2013, Netherlands</td>
<td align="left" rowspan="1" colspan="1">Community/online access panel</td>
<td align="left" rowspan="1" colspan="1">AUDIT; (1) &gt;1 drink (females) or &gt;2 drinks (males) per day, (2) drinking more than 5 days per week; (3) &gt;7 AUDIT</td>
<td align="left" rowspan="1" colspan="1">Internet | home</td>
<td align="left" rowspan="1" colspan="1">PNF | 3 sessions</td>
<td align="left" rowspan="1" colspan="1">1) Alternating vs AO 2) Summative vs AO</td>
<td align="left" rowspan="1" colspan="1">1) 132/135∧; 2) 181/135∧</td>
<td align="left" rowspan="1" colspan="1">Mean drinks per week</td>
<td align="left" rowspan="1" colspan="1">ITT</td>
<td align="left" rowspan="1" colspan="1">6 months</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">1) Yes 2) Yes 3) Yes 4) Yes</td>
<td align="left" rowspan="1" colspan="1">Drinks: 12.9 (11.2) | AUDIT: -</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Suffoletto, 2012, USA</td>
<td align="left" rowspan="1" colspan="1">Emergency department</td>
<td align="left" rowspan="1" colspan="1">Males/females, AUDIT-C ≥4/3</td>
<td align="left" rowspan="1" colspan="1">SMS | home</td>
<td align="left" rowspan="1" colspan="1">Unguided |PNF | 12 weeks</td>
<td align="left" rowspan="1" colspan="1">1) Unguided<sup>i</sup> vs AO; 2) Unguided<sup>j</sup> vs AO</td>
<td align="left" rowspan="1" colspan="1">1) 14/13∧; 2) 12/13∧</td>
<td align="left" rowspan="1" colspan="1">Drinks per drinking day</td>
<td align="left" rowspan="1" colspan="1">CO</td>
<td align="left" rowspan="1" colspan="1">3 months</td>
<td align="left" rowspan="1" colspan="1">13%</td>
<td align="left" rowspan="1" colspan="1">1) Yes 2) Yes 3) Yes 4) No</td>
<td align="left" rowspan="1" colspan="1">Drinks: - | AUDIT: -</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Wallace, 2011, UK</td>
<td align="left" rowspan="1" colspan="1">Alcohol website</td>
<td align="left" rowspan="1" colspan="1">Males/females, AUDIT-C ≥5</td>
<td align="left" rowspan="1" colspan="1">Internet | home</td>
<td align="left" rowspan="1" colspan="1">Unguided |CBT | 3 modules</td>
<td align="left" rowspan="1" colspan="1">Unguided vs CW</td>
<td align="left" rowspan="1" colspan="1">582/695</td>
<td align="left" rowspan="1" colspan="1">Drinks in past week</td>
<td align="left" rowspan="1" colspan="1">ITT</td>
<td align="left" rowspan="1" colspan="1">3 months</td>
<td align="left" rowspan="1" colspan="1">45%</td>
<td align="left" rowspan="1" colspan="1">1) Yes 2) Yes 3) Yes 4) Yes</td>
<td align="left" rowspan="1" colspan="1">36.8 (25.0) | AUDIT: 18.8 (7.3)</td>
</tr>
</tbody>
</table>
</alternatives><table-wrap-foot><fn id="nt101"><label/><p><italic>Notes:</italic> <sup>1–4</sup>: Risk of bias: 1): adequate sequence generation; 2): report of conditions by an independent party; 3): blinding of outcome assessor or using self-report outcomes only; 4): intention to treat analyses; *: in regression analysis coded as NO; ∧ control group reported twice; &amp;: at risk group drinkers only; <bold><sup>a</sup></bold>intervention group size; control group size; <sup>c</sup>full-care intervention; ?stepped-care intervention; <sup>e</sup>brief personalised feedback intervention; <sup>f</sup>brief personalised advice intervention;<sup> g</sup>Alcohol Savvy intervention; <sup>h</sup>Drinker’s Check-Up intervention; <sup>i</sup>text message feedback intervention; <sup>j</sup>text message assessment intervention; <sup>k</sup>1 ‘drink’ contains 10 grams of ethanol; <sup>l</sup>only a subsample included;<sup> m</sup>not all participants randomly allocated; AB alcohol brochure control; AB/H alcohol/health brochure control; AO assessment-only control; AUDIT: Alcohol Use Disorders Identification Test; AUDI-C <sup>brief AUDIT, composite</sup> measure that consists of respondents’ scores on frequency of drinking, drinks per drinking day and frequency of five or more drinks on one occasion; BSC behavioural self-control training; CBT cognitive-behavioural therapy; CO completers-only analysis; CW comparator website control; DO Study dropout; FAST Fast Alcohol Screening Test; GGT gamma-glutamyl transpeptidase test; HB Health booklet control; HBM Health Belief model; HE health education; ITT intention-to-treat analysis; MI motivational interviewing; PFGS personalised feedback with goal setting; PNF personalised normative feedback; SCM stages of change model; TTM transtheoretical model of change.</p></fn></table-wrap-foot></table-wrap></sec><sec id="s2d">
<title>Study Characteristics</title>
<p>Characteristics of the analysed studies are described in <xref ref-type="table" rid="pone-0099912-t001">table 1</xref>. We coded (1) year of study and country of origin; (2) participant characteristics: alcohol consumption level at baseline, recruitment setting, target group; (3) intervention characteristics: therapeutic principles, mode and setting of delivery, guided or unguided self-help format, number of sessions; and (4) other study characteristics: type of control condition, number of participants in each comparative condition, primary outcome measure (how consumed quantities of alcohol were assessed), intention-to-treat (ITT) versus completers-only (CO) analyses, post-treatment assessments in months, dropout rate and risk of bias. The brief self-help alcohol interventions we identified were based on one or more of the following principles: behavioural self-control <xref ref-type="bibr" rid="pone.0099912-Hester2">[40]</xref>, motivational interviewing <xref ref-type="bibr" rid="pone.0099912-Miller1">[41]</xref>, transtheoretical model of change <xref ref-type="bibr" rid="pone.0099912-Prochaska1">[42]</xref>, cognitive-behavioural therapy (CBT, <xref ref-type="bibr" rid="pone.0099912-Kalden1">[43]</xref>), and personalised normative feedback (PNF <xref ref-type="bibr" rid="pone.0099912-Chan1">[44]</xref>).</p>
</sec><sec id="s2e">
<title>Meta-analyses</title>
<p>We first calculated a mean alcohol consumption effect size for each comparison between an alcohol intervention and a control group. Effect sizes were calculated by subtracting the average post-test score of the alcohol self-help group from the average score of the comparison group and dividing the result by the pooled standard deviations of the two groups. This effect size is known as Cohen’s <italic>d</italic>. As the effect size <italic>d</italic> is subject to small-sample bias, it can be adjusted by using a scaling factor, which is multiplied by <italic>d</italic> to arrive at Hedges’s bias-corrected effect size <italic>g</italic>, so that g = d (1−[3/4(n<sub>1</sub>+n<sub>0</sub>]−9). An effect size of 0.50 indicates that the mean of the experimental group is half a standard deviation larger than the mean of the control group. Effect sizes of approximately 0.80 can be considered large, 0.5 as moderate, and 0.2 small <xref ref-type="bibr" rid="pone.0099912-Cohen1">[45]</xref>. Participant adherence to low-risk alcohol guidelines (by either abstaining or not exceeding recommended limits) was assessed in terms of percentages (yes/no).</p>
<p>If means and standard deviations were not reported, we contacted the study authors to obtain these and/or we used the procedures of the Comprehensive Meta-Analysis software (CMA, version 2.2.021) to calculate the effect size using continuous or dichotomous outcomes. In the event these were not available either, we used other statistics (such a <italic>t</italic>- or <italic>p</italic>-value). Where possible, data from intention-to-treat analyses were used; completers-only data were used if the former were unavailable. If more than one alcohol consumption outcome measure was reported in a single study, we averaged the effect sizes from those measures to produce a single summary effect size for use in the meta-analysis, statistically adjusting those calculations to account for variance introduced by the multiple measures <xref ref-type="bibr" rid="pone.0099912-Borenstein1">[46]</xref>.</p>
<p>We calculated the mean effect sizes using a random effects model. This assumes that the included studies were drawn from ‘populations’ of studies that systematically differed from one another (heterogeneity). As a test of homogeneity of effect sizes, we calculated the <italic>I<sup>2</sup></italic> statistic, an indicator of heterogeneity in percentages. A value of 0% indicates no observed heterogeneity, and larger values show increasing heterogeneity, with 25% as low, 50% as moderate and 75% as high <xref ref-type="bibr" rid="pone.0099912-Higgins2">[47]</xref>. As the <italic>I<sup>2</sup></italic> statistic is known to be imprecise <xref ref-type="bibr" rid="pone.0099912-Ioannidis1">[48]</xref>, we calculated the 95% confidence interval using the non-central chi-squared-based approach within the heterogi module in Stata <xref ref-type="bibr" rid="pone.0099912-Orsini1">[49]</xref>. We also estimated numbers needed to treat (NNTs) <xref ref-type="bibr" rid="pone.0099912-Kraemer1">[50]</xref>.</p>
<sec id="s2e1">
<title>Subgroup analyses</title>
<p>In consideration of the literature, ten subgroups analyses were carried out using the mixed effects model, whereby studies within subgroups are pooled with the random effects model (see <xref ref-type="table" rid="pone-0099912-t002">table 2</xref>). Tests for significant differences between subgroups are then performed with the fixed effects model. For continuous variables, we used bivariate meta-regression analyses to test whether there was a significant relationship between each variable and the alcohol effect size, as indicated by a <italic>Z-</italic>value and an associated <italic>p</italic>-value.</p>
<table-wrap id="pone-0099912-t002" position="float"><object-id pub-id-type="doi">10.1371/journal.pone.0099912.t002</object-id><label>Table 2</label><caption>
<title>Effects of low-intensity Internet alcohol treatment on alcohol consumption in comparison with no-intervention controls, and subgroup analyses of associations between effect sizes and study characteristics (Hedges’s <italic>g</italic>).</title>
</caption><alternatives><graphic id="pone-0099912-t002-2" position="float" mimetype="image" xlink:href="info:doi/10.1371/journal.pone.0099912.t002" xlink:type="simple"/>
<table><colgroup span="1"><col align="left" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/><col align="center" span="1"/></colgroup>
<thead>
<tr>
<td align="left" rowspan="1" colspan="1">Experimental/Control</td>
<td align="left" rowspan="1" colspan="1">subgroup</td>
<td align="left" rowspan="1" colspan="1">n comparisons</td>
<td align="left" rowspan="1" colspan="1"><italic>g</italic></td>
<td align="left" rowspan="1" colspan="1">95% CI</td>
<td align="left" rowspan="1" colspan="1"><italic>I<sup>2</sup></italic><sup>b</sup></td>
<td align="left" rowspan="1" colspan="1">95% CI</td>
<td align="left" rowspan="1" colspan="1"><italic>P</italic><sup>d</sup></td>
<td align="left" rowspan="1" colspan="1">NNT<sup>e</sup></td>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="1" colspan="1"><bold><italic>All studies</italic></bold><bold><sup>a</sup></bold></td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">23</td>
<td align="left" rowspan="1" colspan="1">0.20</td>
<td align="left" rowspan="1" colspan="1">0.13–0.27***</td>
<td align="left" rowspan="1" colspan="1">27</td>
<td align="left" rowspan="1" colspan="1">0∼56</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">8.93</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">One effect size per study (lowest excluded)</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">16</td>
<td align="left" rowspan="1" colspan="1">0.23</td>
<td align="left" rowspan="1" colspan="1">0.15–0.32***</td>
<td align="left" rowspan="1" colspan="1">34</td>
<td align="left" rowspan="1" colspan="1">0∼64</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">7.69</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">One effect size per study (highest excluded)</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">16</td>
<td align="left" rowspan="1" colspan="1">0.20</td>
<td align="left" rowspan="1" colspan="1">0.10–0.29***</td>
<td align="left" rowspan="1" colspan="1">39*</td>
<td align="left" rowspan="1" colspan="1">0∼66</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">8.93</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Lowest effect size removed</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">22</td>
<td align="left" rowspan="1" colspan="1">0.20</td>
<td align="left" rowspan="1" colspan="1">0.13–0.27***</td>
<td align="left" rowspan="1" colspan="1">24</td>
<td align="left" rowspan="1" colspan="1">0∼55</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">8.93</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Highest effect size removed</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">22</td>
<td align="left" rowspan="1" colspan="1">0.19</td>
<td align="left" rowspan="1" colspan="1">0.12–0.25***</td>
<td align="left" rowspan="1" colspan="1">20</td>
<td align="left" rowspan="1" colspan="1">0∼53</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">9.43</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"><bold><italic>Subgroup analyses (N = 23)</italic></bold></td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1"/>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Type of control</td>
<td align="left" rowspan="1" colspan="1">Assessment-only</td>
<td align="left" rowspan="1" colspan="1">11</td>
<td align="left" rowspan="1" colspan="1">0.15</td>
<td align="left" rowspan="1" colspan="1">0.06–0.24***</td>
<td align="left" rowspan="1" colspan="1">0</td>
<td align="left" rowspan="1" colspan="1">0∼60</td>
<td align="left" rowspan="1" colspan="1"><bold>.056</bold></td>
<td align="left" rowspan="1" colspan="1">11.90</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Waitlist</td>
<td align="left" rowspan="1" colspan="1">3</td>
<td align="left" rowspan="1" colspan="1">0.48</td>
<td align="left" rowspan="1" colspan="1">0.22–0.73***</td>
<td align="left" rowspan="1" colspan="1">0</td>
<td align="left" rowspan="1" colspan="1">0∼90</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">3.76</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Alcohol brochure</td>
<td align="left" rowspan="1" colspan="1">9</td>
<td align="left" rowspan="1" colspan="1">0.20</td>
<td align="left" rowspan="1" colspan="1">0.08–0.31***</td>
<td align="left" rowspan="1" colspan="1">48</td>
<td align="left" rowspan="1" colspan="1">0∼76</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">8.93</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Blinding of participants</td>
<td align="left" rowspan="1" colspan="1">Yes</td>
<td align="left" rowspan="1" colspan="1">8</td>
<td align="left" rowspan="1" colspan="1">0.16</td>
<td align="left" rowspan="1" colspan="1">0.04–0.28**</td>
<td align="left" rowspan="1" colspan="1">30</td>
<td align="left" rowspan="1" colspan="1">0∼69</td>
<td align="left" rowspan="1" colspan="1">.393</td>
<td align="left" rowspan="1" colspan="1">11.11</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">No</td>
<td align="left" rowspan="1" colspan="1">15</td>
<td align="left" rowspan="1" colspan="1">0.23</td>
<td align="left" rowspan="1" colspan="1">0.14–0.32***</td>
<td align="left" rowspan="1" colspan="1">23</td>
<td align="left" rowspan="1" colspan="1">0∼58</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">7.69</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Analyses</td>
<td align="left" rowspan="1" colspan="1">ITT</td>
<td align="left" rowspan="1" colspan="1">13</td>
<td align="left" rowspan="1" colspan="1">0.22</td>
<td align="left" rowspan="1" colspan="1">0.13–0.31***</td>
<td align="left" rowspan="1" colspan="1">30</td>
<td align="left" rowspan="1" colspan="1">0∼64</td>
<td align="left" rowspan="1" colspan="1">.600</td>
<td align="left" rowspan="1" colspan="1">8.06</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">CO</td>
<td align="left" rowspan="1" colspan="1">10</td>
<td align="left" rowspan="1" colspan="1">0.18</td>
<td align="left" rowspan="1" colspan="1">0.05–0.30**</td>
<td align="left" rowspan="1" colspan="1">19</td>
<td align="left" rowspan="1" colspan="1">0∼60</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">9.80</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Recruitment</td>
<td align="left" rowspan="1" colspan="1">Community</td>
<td align="left" rowspan="1" colspan="1">11</td>
<td align="left" rowspan="1" colspan="1">0.21</td>
<td align="left" rowspan="1" colspan="1">0.11–0.31***</td>
<td align="left" rowspan="1" colspan="1">52*</td>
<td align="left" rowspan="1" colspan="1">4∼76</td>
<td align="left" rowspan="1" colspan="1">.962</td>
<td align="left" rowspan="1" colspan="1">8.47</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Primary care/clinic</td>
<td align="left" rowspan="1" colspan="1">7</td>
<td align="left" rowspan="1" colspan="1">0.21</td>
<td align="left" rowspan="1" colspan="1">0.04–0.39**</td>
<td align="left" rowspan="1" colspan="1">24</td>
<td align="left" rowspan="1" colspan="1">0∼66</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">8.47</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Work</td>
<td align="left" rowspan="1" colspan="1">5</td>
<td align="left" rowspan="1" colspan="1">0.24</td>
<td align="left" rowspan="1" colspan="1">0.05–0.412**</td>
<td align="left" rowspan="1" colspan="1">0</td>
<td align="left" rowspan="1" colspan="1">0∼71</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">7.46</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Population for inclusion</td>
<td align="left" rowspan="1" colspan="1">At-risk drinking cut-off</td>
<td align="left" rowspan="1" colspan="1">12</td>
<td align="left" rowspan="1" colspan="1">0.19</td>
<td align="left" rowspan="1" colspan="1">0.09–0.28***</td>
<td align="left" rowspan="1" colspan="1">40</td>
<td align="left" rowspan="1" colspan="1">0∼70</td>
<td align="left" rowspan="1" colspan="1">.530</td>
<td align="left" rowspan="1" colspan="1">9.43</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">AUDIT (10)/(FAST (1)</td>
<td align="left" rowspan="1" colspan="1">11</td>
<td align="left" rowspan="1" colspan="1">0.24</td>
<td align="left" rowspan="1" colspan="1">0.12–0.35***</td>
<td align="left" rowspan="1" colspan="1">1</td>
<td align="left" rowspan="1" colspan="1">0∼61</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">7.46</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Focus of treatment</td>
<td align="left" rowspan="1" colspan="1">PNF</td>
<td align="left" rowspan="1" colspan="1">9</td>
<td align="left" rowspan="1" colspan="1">0.16</td>
<td align="left" rowspan="1" colspan="1">0.07–0.24***</td>
<td align="left" rowspan="1" colspan="1">0</td>
<td align="left" rowspan="1" colspan="1">0∼65</td>
<td align="left" rowspan="1" colspan="1">.236</td>
<td align="left" rowspan="1" colspan="1">11.11</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Combined</td>
<td align="left" rowspan="1" colspan="1">14</td>
<td align="left" rowspan="1" colspan="1">0.24</td>
<td align="left" rowspan="1" colspan="1">0.13–0.35***</td>
<td align="left" rowspan="1" colspan="1">42*</td>
<td align="left" rowspan="1" colspan="1">0∼69</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">7.46</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Professional guidance</td>
<td align="left" rowspan="1" colspan="1">Yes</td>
<td align="left" rowspan="1" colspan="1">5</td>
<td align="left" rowspan="1" colspan="1">0.23</td>
<td align="left" rowspan="1" colspan="1">0.05–0.41**</td>
<td align="left" rowspan="1" colspan="1">10</td>
<td align="left" rowspan="1" colspan="1">0∼81</td>
<td align="left" rowspan="1" colspan="1">.730</td>
<td align="left" rowspan="1" colspan="1">7.69</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">No</td>
<td align="left" rowspan="1" colspan="1">18</td>
<td align="left" rowspan="1" colspan="1">0.20</td>
<td align="left" rowspan="1" colspan="1">0.12–0.28***</td>
<td align="left" rowspan="1" colspan="1">33</td>
<td align="left" rowspan="1" colspan="1">43∼87</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">8.93</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Number of sessions</td>
<td align="left" rowspan="1" colspan="1">Single</td>
<td align="left" rowspan="1" colspan="1">8</td>
<td align="left" rowspan="1" colspan="1">0.16</td>
<td align="left" rowspan="1" colspan="1">0.08–0.25***</td>
<td align="left" rowspan="1" colspan="1">0</td>
<td align="left" rowspan="1" colspan="1">0∼68</td>
<td align="left" rowspan="1" colspan="1">.399</td>
<td align="left" rowspan="1" colspan="1">11.11</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">More than one</td>
<td align="left" rowspan="1" colspan="1">15</td>
<td align="left" rowspan="1" colspan="1">0.22</td>
<td align="left" rowspan="1" colspan="1">0.12–0.33***</td>
<td align="left" rowspan="1" colspan="1">42*</td>
<td align="left" rowspan="1" colspan="1">0∼68</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">8.06</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Gender</td>
<td align="left" rowspan="1" colspan="1">Male only</td>
<td align="left" rowspan="1" colspan="1">4</td>
<td align="left" rowspan="1" colspan="1">0.26</td>
<td align="left" rowspan="1" colspan="1">0.12–0.40***</td>
<td align="left" rowspan="1" colspan="1">0</td>
<td align="left" rowspan="1" colspan="1">0∼85</td>
<td align="left" rowspan="1" colspan="1">.484</td>
<td align="left" rowspan="1" colspan="1">8.06</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">Male and female</td>
<td align="left" rowspan="1" colspan="1">19</td>
<td align="left" rowspan="1" colspan="1">0.20</td>
<td align="left" rowspan="1" colspan="1">0.11–0.28***</td>
<td align="left" rowspan="1" colspan="1">35</td>
<td align="left" rowspan="1" colspan="1">0∼63</td>
<td align="left" rowspan="1" colspan="1"/>
<td align="left" rowspan="1" colspan="1">8.93</td>
</tr>
</tbody>
</table>
</alternatives><table-wrap-foot><fn id="nt102"><label/><p><italic>Notes:</italic> <bold>bold</bold> – near significance;<sup> a</sup>-1 according to the random effects model;<sup> a</sup>-2: according to the mixed effects model <sup>b</sup>The P-values in this column indicatewhether the Q-statistic is significant (I2-statistics do not include a test of significance).; <sup>c</sup>The P-values in this column indicate whether the difference between the effect sizes in the subgroups is significant.; *P≤0.05; **P&lt;0.01; ***P≤0.001; AUDIT: Alcohol Use Disorders Identification Test; CBT cognitive-behavioural therapy; CI = confidence interval; CO completers-only analysis; DSM = Diagnostic Statistical Manual of Mental Disorders; FAST: Fast Alcohol Screening Test; ITT intention-to-treat analysis; MI motivational interviewing; n comp = number of comparisons; NNT = number needed to treat; PNF personalised normative feedback.</p></fn></table-wrap-foot></table-wrap></sec></sec><sec id="s2f">
<title>Power Calculations</title>
<p>We calculated both beforehand and afterwards how many studies would be needed to ensure sufficient statistical power to identify relevant effects as we expected a small to moderate effect size <xref ref-type="bibr" rid="pone.0099912-Riper1">[26]</xref>, <xref ref-type="bibr" rid="pone.0099912-Riper3">[51]</xref>. The power calculations were carried out according to the procedures described by Borenstein and colleagues <xref ref-type="bibr" rid="pone.0099912-Borenstein1">[46]</xref>. Beforehand we hoped to find enough studies to enable identification of a small effect size of <italic>d</italic> = 0.40 based on the random effects model. The power calculations indicated that this would require at least ten studies with a mean sample size of 70 participants per condition. That conservatively assumes a medium level of between-study variance (τ<sup>2</sup>), a statistical power of .80 and a significance level of α&lt;.05.</p>
</sec><sec id="s2g">
<title>Publication Bias</title>
<p>To detect possible publication bias, we visually examined the funnel plots of the primary outcome measures for symmetry. We conducted Egger’s linear regression test of the intercept to quantify the bias captured by the funnel plot and test whether it was significant <xref ref-type="bibr" rid="pone.0099912-Egger1">[52]</xref>. Duval and Tweedie trim-and-fill procedure was performed to further verify whether the pooled effect size estimate was unbiased <xref ref-type="bibr" rid="pone.0099912-Duval1">[53]</xref>. These procedures were all performed with CMA.</p>
</sec></sec><sec id="s3">
<title>Results</title>
<sec id="s3a">
<title>Selection and Inclusion of Studies</title>
<p>A flowchart depicting our study selection procedure is shown in <xref ref-type="fig" rid="pone-0099912-g001">figure 1</xref>. In reporting the results we followed the guidelines of the PRISMA statement (see <xref ref-type="supplementary-material" rid="pone.0099912.s001">Checklist S1</xref>) <xref ref-type="bibr" rid="pone.0099912-Moher1">[54]</xref>.</p>
</sec><sec id="s3b">
<title>Characteristics of Included Studies</title>
<p><xref ref-type="table" rid="pone-0099912-t001">Table 1</xref> summarises the selected characteristics of the 16 studies (containing 23 comparisons) included in the meta-analysis. The studies assessed a total of 5,612 participants (3,268 in experimental and 2,344 in control conditions) and thus provided sufficient statistical power to detect a small effect size (see section 2.6).</p>
<p>In five studies, sample inclusion was based on self-reported alcohol consumption, using cut-off points indicative of alcohol use exceeding low-risk guidelines, with differing levels for men and women. Five other studies applied the Alcohol Use Identification Test (AUDIT <xref ref-type="bibr" rid="pone.0099912-Saunders2">[55]</xref>) or the Fast Alcohol Screening Test (FAST <xref ref-type="bibr" rid="pone.0099912-Hodgson1">[56]</xref>). Two studies applied both AUDIT and alcohol consumption cut-off points; one selected on the basis of GGT (gamma-glutamyl transpeptidase) testing. Two of the sixteen studies <xref ref-type="bibr" rid="pone.0099912-Doumas1">[57]</xref>, <xref ref-type="bibr" rid="pone.0099912-Pemberton1">[58]</xref> included anyone interested in participating; for these studies, we confined our analysis to subgroups belonging to the at-risk drinking population.</p>
<p>Seven studies applied a single-focus therapeutic strategy, which in six cases was personalised normative feedback (PNF) and in one case a generic health education approach. The other nine studies used combined treatment approaches consisting of motivational interviewing (MI), personalised normative feedback (PNF), cognitive-behavioural therapy (CBT) and/or behavioural self-control and change principles. The control groups represented assessment-only (<italic>n</italic> = 6), waitlisted (<italic>n</italic> = 3) or alcohol information brochure conditions (<italic>n</italic> = 7). The outcome assessments to indicate alcohol consumption were expressed in terms of mean standard drinks per drinking day, total numbers of standard drinks in the previous week, mean standard drinks per drinking occasion or amounts of alcohol in grams.</p>
<p>The risk of bias varied among the studies (<xref ref-type="table" rid="pone-0099912-t001">table 1</xref>), with 14 studies reporting adequate sequence generation, 6 reporting allocation to conditions by an independent party, 15 reporting blinding of outcome assessors or using self-report outcomes only, and 10 using intention-to-treat analyses. Dropout rates varied from 0% to 42%.</p>
</sec><sec id="s3c">
<title>Meta-analysis</title>
<p>The effect of low-intensity Internet-based alcohol interventions to reduce alcohol consumption in comparison to controls was small but significant at post-test (<italic>g</italic> = 0.20, random effects model, 95% CI: 0.13–0.27, <italic>p</italic>&lt;.001, NNT = 8.93). Results are shown in <xref ref-type="fig" rid="pone-0099912-g002">figure 2</xref> (from high to low study effect sizes) and <xref ref-type="table" rid="pone-0099912-t002">table 2</xref>. Heterogeneity was low but with a moderate confidence interval (<italic>I<sup>2</sup></italic> = 27, 95% CI: 0–56). A post-hoc power calculation showed that our set of studies had sufficient statistical power (0.99) on the basis of the random effects model (with a low level of between-study variance, τ<sup>2</sup> = .001, and a significance level of α &lt;.05).</p>
<fig id="pone-0099912-g002" position="float"><object-id pub-id-type="doi">10.1371/journal.pone.0099912.g002</object-id><label>Figure 2</label><caption>
<title>Results of meta-analysis: forest plot.</title>
</caption><graphic mimetype="image" xlink:href="info:doi/10.1371/journal.pone.0099912.g002" position="float" xlink:type="simple"/></fig>
<p>Seven studies <xref ref-type="bibr" rid="pone.0099912-Blankers2">[37]</xref>, <xref ref-type="bibr" rid="pone.0099912-Doumas1">[57]</xref>–<xref ref-type="bibr" rid="pone.0099912-Suffoletto1">[62]</xref> compared more than one group receiving differing types of Internet-based brief treatment with a single control group, so that our analysis included multiple comparisons from these studies. The fact that the comparisons were not independent of one another could have artificially reduced the heterogeneity of the analysed studies, thereby affecting the pooled effect size. To test this, we carried out sensitivity analyses that included only one effect size per study. As <xref ref-type="table" rid="pone-0099912-t002">table 2</xref> shows, removal of the comparisons with the highest effect sizes had almost no influence on the pooled effect size nor did removing the comparisons with the lowest effect sizes. Removal of the one guided intervention comparison with the highest effect size (in Blankers <xref ref-type="bibr" rid="pone.0099912-Blankers2">[37]</xref>) did not influence the observed effect size either, nor did removal of that with the lowest effect size <xref ref-type="bibr" rid="pone.0099912-Suffoletto1">[62]</xref>.</p>
</sec><sec id="s3d">
<title>Mean Alcohol Consumption Reduction and Drinking within Low Risk Guidelines</title>
<p>On average, the intervention participants were drinking 2,2 alcohol consumptions (22 grams of ethanol) less per week at post-treatment than controls (<italic>n</italic> = 14; 95% CI: 0.87–3.46, <italic>p</italic> = .001, I<sup>2</sup> = 0, <italic>p</italic>&lt;.001; mean difference). Post-test differences <xref ref-type="bibr" rid="pone.0099912-Blankers2">[37]</xref>, <xref ref-type="bibr" rid="pone.0099912-Schulz1">[61]</xref>, <xref ref-type="bibr" rid="pone.0099912-Boon1">[63]</xref>–<xref ref-type="bibr" rid="pone.0099912-Riper4">[65]</xref>) revealed that intervention participants were significantly more likely than controls to have reduced their alcohol consumption to within the low-risk guidelines as compared to controls (<italic>n</italic> = 6; RD 0.13, 95% CI: 0.09–0.17, <italic>p</italic>&lt;.001, I<sup>2</sup> = 0, non-significant).</p>
</sec><sec id="s3e">
<title>Subgroup Analyses</title>
<p>Subgroup analyses revealed no significant differences between study characteristics and effect sizes for alcohol consumption (see <xref ref-type="table" rid="pone-0099912-t002">table 2</xref>). The differences between types of control conditions bordered on significance (<italic>p</italic> = .056). We found a higher effect size for decreased alcohol consumption for studies applying a waitlist control condition (<italic>g</italic> = 0.48) than those applying an alcohol brochure condition (<italic>g</italic> = 0.20) or an assessment-only condition (<italic>g</italic> = 0.15).</p>
</sec><sec id="s3f">
<title>Follow-up Assessments</title>
<p>No significant differences in effect remained at follow-up (6 to 12 months after baseline) between the six unguided interventions (8 comparisons) and control groups (<italic>g</italic> = 0.06, 95% CI: −0.14–0.25, <italic>p</italic> = .567, random effects model) for which such follow-up assessments were available. No follow-up assessments were available for the guided interventions.</p>
</sec><sec id="s3g">
<title>Regression Analyses</title>
<p>Meta-regression analyses with Hedges’s <italic>g</italic> as the dependent variable uncovered no significant associations between effect size and either the number of alcohol intervention sessions (β = −0.0001, 95% CI: −0.004–0.003, <italic>p</italic> = .938) or the risk of bias (β = 0.068, 95% CI: −0.15–0.01, <italic>p</italic> = .089) in the studies assessed.</p>
</sec><sec id="s3h">
<title>Publication Bias</title>
<p>There was evidence of publication bias in terms of Duval and Tweedie’s trim-and-fill method. After adjustment for missing studies, the effect size for decreased alcohol consumption diminished from <italic>g</italic> = 0.20 to <italic>g</italic> = 0.14 (95% CI: 0.06–0.22; trimmed studies <italic>n</italic> = 8, random effects model). Egger’s test indicated an asymmetric funnel plot (<italic>p</italic> = .028, two-tailed).</p>
</sec></sec><sec id="s4">
<title>Discussion</title>
<p>This meta-analysis showed a small but significant overall effect size (<italic>g</italic> = 0.20) in favour of low-intensity Internet-based self-help interventions to curb alcohol misuse over control conditions. At post-treatment, intervention participants were consuming an average of 22 grams of alcohol less per week than controls. The reduction appears lower than those found in analyses of face-to-face brief interventions in primary care. The latter include a Cochrane Collaboration systematic review of 29 primary care trials <xref ref-type="bibr" rid="pone.0099912-Kaner1">[30]</xref>, which reported a significantly reduced weekly consumption of 38 grams at one-year follow-up (see also the study by Jonas and colleagues <xref ref-type="bibr" rid="pone.0099912-Jonas1">[15]</xref>). In our study, Internet intervention participants were 13% more likely than controls to stay within the guidelines after treatment (<italic>n</italic> = 6). This is in line with the study of Jonas and colleagues <xref ref-type="bibr" rid="pone.0099912-Jonas1">[15]</xref> who showed that those receiving primary care alcohol interventions were 11% more likely to do so when compared with controls.</p>
<p>The overall effect size in this meta-analysis is lower than, the effect size found in our previous study that focused solely on <italic>unguided</italic> e-interventions (7 studies, <italic>g</italic> = 0.39) <xref ref-type="bibr" rid="pone.0099912-Riper1">[26]</xref>. Some explanations for this may lie in the three-times-higher number of comparisons involved in the current analysis and the fact that studies with null findings were now included <xref ref-type="bibr" rid="pone.0099912-Hansen1">[60]</xref>, <xref ref-type="bibr" rid="pone.0099912-Wallace1">[66]</xref>. The current overall effect also compares with meta-analyses of face-to-face primary care samples <xref ref-type="bibr" rid="pone.0099912-Moyer1">[3]</xref>, <xref ref-type="bibr" rid="pone.0099912-Kaner1">[30]</xref>, <xref ref-type="bibr" rid="pone.0099912-ODonnell1">[67]</xref>, <xref ref-type="bibr" rid="pone.0099912-Moyer2">[68]</xref> and of non-clinical samples performing postal self-help interventions based on bibliotherapy <xref ref-type="bibr" rid="pone.0099912-Apodaca1">[69]</xref>–<xref ref-type="bibr" rid="pone.0099912-Burke1">[71]</xref>. These studies all showed significant small to moderate effect sizes for curbing alcohol misuse. We found no significant differences between experimental and control conditions for those studies that assessed follow-up outcomes up to twelve months. Such a decay of intervention effects is not uncommon; larger effect sizes are generally found at the earliest follow-ups <xref ref-type="bibr" rid="pone.0099912-Jonas1">[15]</xref>, <xref ref-type="bibr" rid="pone.0099912-Moyer2">[68]</xref>. Some studies of brief interventions for problem drinking have nonetheless reported positive influences on alcohol reduction up to four years later <xref ref-type="bibr" rid="pone.0099912-ODonnell1">[67]</xref> and on mortality <xref ref-type="bibr" rid="pone.0099912-Cuijpers3">[72]</xref>.</p>
<sec id="s4a">
<title>Subgroup Analyses</title>
<p>Results of the subgroup analyses did not reveal any significant differences between experimental and control conditions. All these results need to be interpreted with caution, as the number of studies included in the subgroup analyses was low. This means that there where either no real differences between these conditions or that real difference may have gone undetected. The variation in types of control predictors was of borderline significance (<italic>p</italic> = .056) in terms of effect. A moderate effect size was found for studies using waitlist control conditions, while those with assessment-only or alcohol brochure control showed small ones. Other studies have similarly reported higher effect sizes for intervention studies that used waitlisted groups as comparators <xref ref-type="bibr" rid="pone.0099912-Cunningham3">[73]</xref>. One explanation could be that waitlisted participants tend to delay behavioural change because they anticipate professional help in the near future; that could cause overestimation of the intervention effect.</p>
<p>We did not find a significantly greater effect size for guided (<italic>g</italic> = 0.23) than for unguided (<italic>g</italic> = 0.20) alcohol interventions, even though such significant differences in benefit have been overwhelmingly established for web-based treatment of depression and anxiety <xref ref-type="bibr" rid="pone.0099912-Richards1">[34]</xref>, <xref ref-type="bibr" rid="pone.0099912-Donker1">[74]</xref>. Our lack of significant effect might be due to the fact that many participants in web-based alcohol interventions are first-time help seekers; they may hence derive health gains from their first formal attempt at behavioural change, whether unguided or guided. Alternatively, a real difference may have gone undetected as a consequence of the low number of guided interventions in our analysis (5 comparisons. Only the Blankers and colleagues <xref ref-type="bibr" rid="pone.0099912-Blankers2">[37]</xref>, and the Doumas and Hannah <xref ref-type="bibr" rid="pone.0099912-Doumas1">[57]</xref> studies provided direct comparisons between guided and unguided interventions. Both showed a small, but non significant, difference in effect in terms of alcohol consumption reduction in favour of guided interventions. These non-significant results are probably due to lack of power in both studies as well.</p>
<p>In contrast with our previous analysis from 2011 <xref ref-type="bibr" rid="pone.0099912-Riper1">[26]</xref>, we now found no significant differences in alcohol reduction between single-session interventions and more extended ones. Although the literature is somewhat inconclusive <xref ref-type="bibr" rid="pone.0099912-Moyer3">[75]</xref>, it provides some confirmation for our current findings <xref ref-type="bibr" rid="pone.0099912-Kaner1">[30]</xref>, <xref ref-type="bibr" rid="pone.0099912-Moyer2">[68]</xref>, <xref ref-type="bibr" rid="pone.0099912-Kaner2">[76]</xref>.</p>
<p>Web-based interventions may offer considerable promise for reducing alcohol misuse by women. We found no difference in alcohol consumption outcomes between all-male and mixed-gender samples, whereas several studies on face-to-face alcohol interventions in primary care had reported that men were more likely to benefit than women <xref ref-type="bibr" rid="pone.0099912-Kaner1">[30]</xref>, <xref ref-type="bibr" rid="pone.0099912-ODonnell1">[67]</xref>. In the case of Internet-based interventions for alcohol misuse, however, female uptake appears equally as high as male uptake <xref ref-type="bibr" rid="pone.0099912-Riper2">[28]</xref>, <xref ref-type="bibr" rid="pone.0099912-Cunningham4">[77]</xref> and have been seen to have similar impacts on female and on male drinking, or possibly even greater influence on females, as suggested by Riper and colleagues (2008, <xref ref-type="bibr" rid="pone.0099912-Riper5">[78]</xref>).</p>
<p>No difference in effect sizes emerged between studies that used cut-off points in alcohol consumption as study inclusion criteria and those that applied stricter measurements such as AUDIT <xref ref-type="bibr" rid="pone.0099912-Saunders2">[55]</xref>. AUDIT scores among the latter were high (averaging around 20, indicating a potentially high risk of alcohol dependence amongst participants. Internet interventions might thus well be effective for a broad spectrum of people who misuse alcohol. Just as in many trials of brief alcohol interventions and routine practice studies <xref ref-type="bibr" rid="pone.0099912-Purshouse1">[18]</xref>, <xref ref-type="bibr" rid="pone.0099912-Robinson1">[79]</xref>, the studies in our analysis did not conduct diagnostic interviews to assess for alcohol dependence. This lack of actual diagnoses also hampers any attempt to use the available data to test the common view that self-help interventions are particularly suited to people with less serious alcohol problems, but less appropriate for those with alcohol dependence <xref ref-type="bibr" rid="pone.0099912-Moyer1">[3]</xref>, <xref ref-type="bibr" rid="pone.0099912-Saitz1">[80]</xref>.</p>
<p>Several limitations underlie our meta-analysis that may have affected our overall results. First, as indicated the number of studies included in the subgroup analyses was low. The resulting insufficient statistical power may call into question our outcomes whereby no significant difference between a number of conditions could be observed. Second, some included studies had substantial dropout rates (above 30%; see <xref ref-type="table" rid="pone-0099912-t001">table 1</xref>). High study (and treatment) dropout rates are a common phenomenon in both online and offline self-help interventions for alcohol misuse and in Internet interventions in general <xref ref-type="bibr" rid="pone.0099912-Eysenbach1">[81]</xref>, <xref ref-type="bibr" rid="pone.0099912-Postel2">[82]</xref>. Third, the impact of online self-help in reducing alcohol consumption may have been underestimated here because control group drinking was also assessed; such assessment alone possibly motivates controls to reduce their consumption <xref ref-type="bibr" rid="pone.0099912-McCambridge1">[83]</xref>, <xref ref-type="bibr" rid="pone.0099912-McCambridge2">[84]</xref>. Last but not least, we were not able to evaluate possible negative side-effects of Internet-based interventions for problem drinking, as the studies lack reports on such effects.</p>
</sec><sec id="s4b">
<title>Clinical Implications</title>
<p>The results of this study support the use of guided and unguided Internet-based self-help interventions for curbing alcohol misuse in various settings (primary health care, work environments and the community). Although the overall effect size for these interventions was small, the public health impact could be substantial if large numbers of people who misuse alcohol were to take part in these interventions. Decreasing alcohol consumption as well as abstinence and adherence to low-risk guidelines are health benefits in their own right and potential predictors of longer-term maintenance of decreased alcohol consumption <xref ref-type="bibr" rid="pone.0099912-Roerecke1">[85]</xref>. A modelling study by Smit and colleagues <xref ref-type="bibr" rid="pone.0099912-Smit1">[86]</xref> has suggested that if online interventions were to partially replace conventional face-to-face brief alcohol interventions, that could sustain comparable levels of population health at lower costs.</p>
</sec><sec id="s4c">
<title>Future Research</title>
<p>Future studies should try to assess which type (s) of alcohol misuse populations could benefit most from brief online alcohol interventions. More studies with longer-term follow-up periods (over 12 months) are needed, too, to assess the maintenance of intervention effects over time in terms of reduced consumption and other health outcomes. Studies focusing on the effects of guided self-help interventions in curbing alcohol misuse, in direct comparison with unguided interventions, could shed light on whether the former produce better outcomes and, if so, at what costs. It is also important to investigate whether combining low-intensity Internet interventions with brief face-to-face interventions (blending of channels) would increase the effectiveness of interventions to curb alcohol misuse.</p>
</sec></sec><sec id="s5">
<title>Conclusion</title>
<p>Internet interventions are capable of reaching out effectively to the large group of people who engage in alcohol misuse. From a public health perspective, this justifies an upscaling of such interventions in routine practice as well as in a wide range of community settings.</p>
</sec><sec id="s6">
<title>Supporting Information</title>
<supplementary-material id="pone.0099912.s001" mimetype="application/msword" xlink:href="info:doi/10.1371/journal.pone.0099912.s001" position="float" xlink:type="simple"><label>Checklist S1</label><caption>
<p>PRISMA checklist.</p>
<p>(DOC)</p>
</caption></supplementary-material></sec></body>
<back><ref-list>
<title>References</title>
<ref id="pone.0099912-Whiteford1"><label>1</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Whiteford</surname><given-names>HA</given-names></name>, <name name-style="western"><surname>Degenhardt</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Rehm</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Baxter</surname><given-names>AJ</given-names></name>, <name name-style="western"><surname>Ferrari</surname><given-names>AJ</given-names></name>, <etal>et al</etal>. (<year>2013</year>) <article-title>Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010</article-title>. <source>Lancet</source> <volume>382</volume>: <fpage>1575</fpage>–<lpage>1586</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Tang1"><label>2</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Tang</surname><given-names>YL</given-names></name>, <name name-style="western"><surname>Xiang</surname><given-names>XJ</given-names></name>, <name name-style="western"><surname>Wang</surname><given-names>XY</given-names></name>, <name name-style="western"><surname>Cubells</surname><given-names>JF</given-names></name>, <name name-style="western"><surname>Babor</surname><given-names>TF</given-names></name>, <etal>et al</etal>. (<year>2013</year>) <article-title>Alcohol and alcohol-related harm in China: policy changes needed</article-title>. <source>Bull World Health Organ</source> <volume>91</volume>: <fpage>270</fpage>–<lpage>276</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Moyer1"><label>3</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Moyer</surname><given-names>VA</given-names></name> (<year>2013</year>) <article-title>Screening and behavioral counseling interventions in primary care to reduce alcohol misuse: U.S. preventive services task force recommendation statement</article-title>. <source>Ann Intern Med</source> <volume>159</volume>: <fpage>210</fpage>–<lpage>218</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Saunders1"><label>4</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Saunders</surname><given-names>JB</given-names></name>, <name name-style="western"><surname>Lee</surname><given-names>NK</given-names></name> (<year>2000</year>) <article-title>Hazardous alcohol use: its delineation as a subthreshold disorder, and approaches to its diagnosis and management</article-title>. <source>Compr Psychiatry</source> <volume>41</volume>: <fpage>95</fpage>–<lpage>103</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-WHO1"><label>5</label>
<mixed-citation publication-type="other" xlink:type="simple">WHO (2000) International guide for monitoring alcohol consumption and related harm. Geneva.: World Health Organization.</mixed-citation>
</ref>
<ref id="pone.0099912-Degenhardt1"><label>6</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Degenhardt</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Whiteford</surname><given-names>HA</given-names></name>, <name name-style="western"><surname>Ferrari</surname><given-names>AJ</given-names></name>, <name name-style="western"><surname>Baxter</surname><given-names>AJ</given-names></name>, <name name-style="western"><surname>Charlson</surname><given-names>FJ</given-names></name>, <etal>et al</etal>. (<year>2013</year>) <article-title>Global burden of disease attributable to illicit drug use and dependence: findings from the Global Burden of Disease Study 2010</article-title>. <source>Lancet</source> <volume>382</volume>: <fpage>1564</fpage>–<lpage>1574</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Grucza1"><label>7</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Grucza</surname><given-names>RA</given-names></name>, <name name-style="western"><surname>Bucholz</surname><given-names>KK</given-names></name>, <name name-style="western"><surname>Rice</surname><given-names>JP</given-names></name>, <name name-style="western"><surname>Bierut</surname><given-names>LJ</given-names></name> (<year>2008</year>) <article-title>Secular trends in the lifetime prevalence of alcohol dependence in the United States: a re-evaluation</article-title>. <source>Alcohol Clin Exp Res</source> <volume>32</volume>: <fpage>763</fpage>–<lpage>770</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Watson1"><label>8</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Watson</surname><given-names>HE</given-names></name> (<year>1999</year>) <article-title>Minimal interventions for problem drinkers: a review of the literature</article-title>. <source>J Adv Nurs</source> <volume>30</volume>: <fpage>513</fpage>–<lpage>519</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Parry1"><label>9</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Parry</surname><given-names>CD</given-names></name>, <name name-style="western"><surname>Patra</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Rehm</surname><given-names>J</given-names></name> (<year>2011</year>) <article-title>Alcohol consumption and non-communicable diseases: epidemiology and policy implications</article-title>. <source>Addiction</source> <volume>106</volume>: <fpage>1718</fpage>–<lpage>1724</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Rehm1"><label>10</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Rehm</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Mathers</surname><given-names>C</given-names></name>, <name name-style="western"><surname>Popova</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Thavorncharoensap</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Teerawattananon</surname><given-names>Y</given-names></name>, <etal>et al</etal>. (<year>2009</year>) <article-title>Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders</article-title>. <source>Lancet</source> <volume>373</volume>: <fpage>2223</fpage>–<lpage>2233</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Cunningham1"><label>11</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Cunningham</surname><given-names>JA</given-names></name>, <name name-style="western"><surname>Breslin</surname><given-names>FC</given-names></name> (<year>2004</year>) <article-title>Only one in three people with alcohol abuse or dependence ever seek treatment</article-title>. <source>Addict Behav</source> <volume>29</volume>: <fpage>221</fpage>–<lpage>223</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-KoskiJanne1"><label>12</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Koski-Janne</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Cunningham</surname><given-names>J</given-names></name> (<year>2001</year>) <article-title>Interest in different forms of self-help in a general population sample of drinkers</article-title>. <source>Addict Behav</source> <volume>26</volume>: <fpage>91</fpage>–<lpage>99</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Nilsen1"><label>13</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Nilsen</surname><given-names>P</given-names></name>, <name name-style="western"><surname>McCambridge</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Karlsson</surname><given-names>N</given-names></name>, <name name-style="western"><surname>Bendtsen</surname><given-names>P</given-names></name> (<year>2011</year>) <article-title>Brief interventions in routine health care: a population-based study of conversations about alcohol in Sweden</article-title>. <source>Addiction</source> <volume>106</volume>: <fpage>1748</fpage>–<lpage>1756</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Wilson1"><label>14</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Wilson</surname><given-names>GB</given-names></name>, <name name-style="western"><surname>Heather</surname><given-names>N</given-names></name>, <name name-style="western"><surname>Kaner</surname><given-names>EF</given-names></name> (<year>2011</year>) <article-title>New developments in brief interventions to treat problem drinking in nonspecialty health care settings</article-title>. <source>Curr Psychiatry Rep</source> <volume>13</volume>: <fpage>422</fpage>–<lpage>429</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Jonas1"><label>15</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Jonas</surname><given-names>DE</given-names></name>, <name name-style="western"><surname>Garbutt</surname><given-names>JC</given-names></name>, <name name-style="western"><surname>Amick</surname><given-names>HR</given-names></name>, <name name-style="western"><surname>Brown</surname><given-names>JM</given-names></name>, <name name-style="western"><surname>Brownley</surname><given-names>KA</given-names></name>, <etal>et al</etal>. (<year>2012</year>) <article-title>Behavioral counseling after screening for alcohol misuse in primary care: a systematic review and meta-analysis for the U.S. Preventive Services Task Force</article-title>. <source>Ann Intern Med</source> <volume>157</volume>: <fpage>645</fpage>–<lpage>654</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Jonas2"><label>16</label>
<mixed-citation publication-type="other" xlink:type="simple">Jonas DE, Garbutt JC, Brown JM, Amick HR, Brownley KA, et al. (2012) Screening, Behavioral Counseling, and Referral in Primary Care To Reduce Alcohol Misuse. Rockville (MD): Agency for Healthcare Research and Quality (US). Report No.: 12-EHC055-EF.</mixed-citation>
</ref>
<ref id="pone.0099912-Latimer1"><label>17</label>
<mixed-citation publication-type="other" xlink:type="simple">Latimer N, Guillaume L (2009) Prevention and early identification of alcohol use disorders in adults and young people: screening and brief interventions: cost effectiveness review. Sheffield: ScHARR Public Health Collaborating Centre.</mixed-citation>
</ref>
<ref id="pone.0099912-Purshouse1"><label>18</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Purshouse</surname><given-names>RC</given-names></name>, <name name-style="western"><surname>Brennan</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Rafia</surname><given-names>R</given-names></name>, <name name-style="western"><surname>Latimer</surname><given-names>NR</given-names></name>, <name name-style="western"><surname>Archer</surname><given-names>RJ</given-names></name>, <etal>et al</etal>. (<year>2013</year>) <article-title>Modelling the cost-effectiveness of alcohol screening and brief interventions in primary care in England</article-title>. <source>Alcohol Alcohol</source> <volume>48</volume>: <fpage>180</fpage>–<lpage>188</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Tariq1"><label>19</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Tariq</surname><given-names>L</given-names></name>, <name name-style="western"><surname>van den Berg</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Hoogenveen</surname><given-names>RT</given-names></name>, <name name-style="western"><surname>van Baal</surname><given-names>PH</given-names></name> (<year>2009</year>) <article-title>Cost-effectiveness of an opportunistic screening programme and brief intervention for excessive alcohol use in primary care</article-title>. <source>PLoS One</source> <volume>4</volume>: <fpage>e5696</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Mdege1"><label>20</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Mdege</surname><given-names>ND</given-names></name>, <name name-style="western"><surname>Fayter</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Watson</surname><given-names>JM</given-names></name>, <name name-style="western"><surname>Stirk</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Sowden</surname><given-names>A</given-names></name>, <etal>et al</etal>. (<year>2013</year>) <article-title>Interventions for reducing alcohol consumption among general hospital inpatient heavy alcohol users: a systematic review</article-title>. <source>Drug Alcohol Depend</source> <volume>131</volume>: <fpage>1</fpage>–<lpage>22</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Watson2"><label>21</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Watson</surname><given-names>JM</given-names></name>, <name name-style="western"><surname>Fayter</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Mdege</surname><given-names>N</given-names></name>, <name name-style="western"><surname>Stirk</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Sowden</surname><given-names>AJ</given-names></name>, <etal>et al</etal>. (<year>2013</year>) <article-title>Interventions for alcohol and drug problems in outpatient settings: a systematic review</article-title>. <source>Drug Alcohol Rev</source> <volume>32</volume>: <fpage>356</fpage>–<lpage>367</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Pedersen1"><label>22</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Pedersen</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Oppedal</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Egund</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Tonnesen</surname><given-names>H</given-names></name> (<year>2011</year>) <article-title>Will emergency and surgical patients participate in and complete alcohol interventions? A systematic review</article-title>. <source>BMC Surg</source> <volume>11</volume>: <fpage>26</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Osilla1"><label>23</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Osilla</surname><given-names>KC</given-names></name>, <name name-style="western"><surname>Van Busum</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Schnyer</surname><given-names>C</given-names></name>, <name name-style="western"><surname>Larkin</surname><given-names>JW</given-names></name>, <name name-style="western"><surname>Eibner</surname><given-names>C</given-names></name>, <etal>et al</etal>. (<year>2012</year>) <article-title>Systematic review of the impact of worksite wellness programs</article-title>. <source>Am J Manag Care</source> <volume>18</volume>: <fpage>e68</fpage>–<lpage>e81</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Hester1"><label>24</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Hester</surname><given-names>RK</given-names></name>, <name name-style="western"><surname>Lenberg</surname><given-names>KL</given-names></name>, <name name-style="western"><surname>Campbell</surname><given-names>W</given-names></name>, <name name-style="western"><surname>Delaney</surname><given-names>HD</given-names></name> (<year>2013</year>) <article-title>Overcoming Addictions, a Web-based application, and SMART Recovery, an online and in-person mutual help group for problem drinkers, part 1: three-month outcomes of a randomized controlled trial</article-title>. <source>J Med Internet Res</source> <volume>15</volume>: <fpage>e134</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-White1"><label>25</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>White</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Kavanagh</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Stallman</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Klein</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Kay-Lambkin</surname><given-names>F</given-names></name>, <etal>et al</etal>. (<year>2010</year>) <article-title>Online alcohol interventions: a systematic review</article-title>. <source>J Med Internet Res</source> <volume>12</volume>: <fpage>e62</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Riper1"><label>26</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Riper</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Spek</surname><given-names>V</given-names></name>, <name name-style="western"><surname>Boon</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Conijn</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Kramer</surname><given-names>J</given-names></name>, <etal>et al</etal>. (<year>2011</year>) <article-title>Effectiveness of E-self-help interventions for curbing adult problem drinking: a meta-analysis</article-title>. <source>J Med Internet Res</source> <volume>13</volume>: <fpage>e42</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Cunningham2"><label>27</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Cunningham</surname><given-names>JA</given-names></name>, <name name-style="western"><surname>Wild</surname><given-names>TC</given-names></name>, <name name-style="western"><surname>Cordingley</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Van Mierlo</surname><given-names>T</given-names></name>, <name name-style="western"><surname>Humphreys</surname><given-names>K</given-names></name> (<year>2009</year>) <article-title>A randomized controlled trial of an internet-based intervention for alcohol abusers</article-title>. <source>Addiction</source> <volume>104</volume>: <fpage>2023</fpage>–<lpage>2032</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Riper2"><label>28</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Riper</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Kramer</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Conijn</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Smit</surname><given-names>F</given-names></name>, <name name-style="western"><surname>Schippers</surname><given-names>G</given-names></name>, <etal>et al</etal>. (<year>2009</year>) <article-title>Translating effective web-based self-help for problem drinking into the real world</article-title>. <source>Alcohol Clin Exp Res</source> <volume>33</volume>: <fpage>1401</fpage>–<lpage>1408</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Vernon1"><label>29</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Vernon</surname><given-names>ML</given-names></name> (<year>2010</year>) <article-title>A review of computer-based alcohol problem services designed for the general public</article-title>. <source>J Subst Abuse Treat</source> <volume>38</volume>: <fpage>203</fpage>–<lpage>211</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Kaner1"><label>30</label>
<mixed-citation publication-type="other" xlink:type="simple">Kaner EF, Beyer F, Dickinson HO, Pienaar E, Campbell F, et al. (2007) Effectiveness of brief alcohol interventions in primary care populations. Cochrane Database Syst Rev CD004148.</mixed-citation>
</ref>
<ref id="pone.0099912-Rooke1"><label>31</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Rooke</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Thorsteinsson</surname><given-names>E</given-names></name>, <name name-style="western"><surname>Karpin</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Copeland</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Allsop</surname><given-names>D</given-names></name> (<year>2010</year>) <article-title>Computer-delivered interventions for alcohol and tobacco use: a meta-analysis</article-title>. <source>Addiction</source> <volume>105</volume>: <fpage>1381</fpage>–<lpage>1390</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Portnoy1"><label>32</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Portnoy</surname><given-names>DB</given-names></name>, <name name-style="western"><surname>Scott-Sheldon</surname><given-names>LA</given-names></name>, <name name-style="western"><surname>Johnson</surname><given-names>BT</given-names></name>, <name name-style="western"><surname>Carey</surname><given-names>MP</given-names></name> (<year>2008</year>) <article-title>Computer-delivered interventions for health promotion and behavioral risk reduction: a meta-analysis of 75 randomized controlled trials, 1988–2007</article-title>. <source>Prev Med</source> <volume>47</volume>: <fpage>3</fpage>–<lpage>16</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Blankers1"><label>33</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Blankers</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Nabitz</surname><given-names>U</given-names></name>, <name name-style="western"><surname>Smit</surname><given-names>F</given-names></name>, <name name-style="western"><surname>Koeter</surname><given-names>MW</given-names></name>, <name name-style="western"><surname>Schippers</surname><given-names>GM</given-names></name> (<year>2012</year>) <article-title>Economic evaluation of internet-based interventions for harmful alcohol use alongside a pragmatic randomized controlled trial</article-title>. <source>J Med Internet Res</source> <volume>14</volume>: <fpage>e134</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Richards1"><label>34</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Richards</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Richardson</surname><given-names>T</given-names></name> (<year>2012</year>) <article-title>Computer-based psychological treatments for depression: a systematic review and meta-analysis</article-title>. <source>Clin Psychol Rev</source> <volume>32</volume>: <fpage>329</fpage>–<lpage>342</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Cuijpers1"><label>35</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Cuijpers</surname><given-names>P</given-names></name>, <name name-style="western"><surname>Marks</surname><given-names>IM</given-names></name>, <name name-style="western"><surname>van Straten</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Cavanagh</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Gega</surname><given-names>L</given-names></name>, <etal>et al</etal>. (<year>2009</year>) <article-title>Computer-aided psychotherapy for anxiety disorders: a meta-analytic review</article-title>. <source>Cogn Behav Ther</source> <volume>38</volume>: <fpage>66</fpage>–<lpage>82</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Cuijpers2"><label>36</label>
<mixed-citation publication-type="other" xlink:type="simple">Cuijpers P, Donker T, van Straten A, Li J, Andersson G (2010) Is guided self-help as effective as face-to-face psychotherapy for depression and anxiety disorders? A systematic review and meta-analysis of comparative outcome studies. Psychol Med 1–15.</mixed-citation>
</ref>
<ref id="pone.0099912-Blankers2"><label>37</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Blankers</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Koeter</surname><given-names>MW</given-names></name>, <name name-style="western"><surname>Schippers</surname><given-names>GM</given-names></name> (<year>2011</year>) <article-title>Internet therapy versus internet self-help versus no treatment for problematic alcohol use: A randomized controlled trial</article-title>. <source>J Consult Clin Psychol</source> <volume>79</volume>: <fpage>330</fpage>–<lpage>341</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Postel1"><label>38</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Postel</surname><given-names>MG</given-names></name>, <name name-style="western"><surname>de Haan</surname><given-names>HA</given-names></name>, <name name-style="western"><surname>ter Huurne</surname><given-names>ED</given-names></name>, <name name-style="western"><surname>Becker</surname><given-names>ES</given-names></name>, <name name-style="western"><surname>de Jong</surname><given-names>CA</given-names></name> (<year>2010</year>) <article-title>Effectiveness of a web-based intervention for problem drinkers and reasons for dropout: randomized controlled trial</article-title>. <source>J Med Internet Res</source> <volume>12</volume>: <fpage>e68</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Higgins1"><label>39</label>
<mixed-citation publication-type="other" xlink:type="simple">Higgins JPT, Green S (2008 February) Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0. The Cochrane Collaboration. Available.</mixed-citation>
</ref>
<ref id="pone.0099912-Hester2"><label>40</label>
<mixed-citation publication-type="other" xlink:type="simple">Hester RK (1995) Behavioral self-control training. In: Hester RK, Miller WR, editors. Handbook of Alcoholism Treatment Approaches: Effective Alternatives. Needham Heights, MA: Allyn and Bacon. 148–159.</mixed-citation>
</ref>
<ref id="pone.0099912-Miller1"><label>41</label>
<mixed-citation publication-type="other" xlink:type="simple">Miller WR, Rollnick S (2002) Motivational Interviewing: Preparing people to change addictive behavior. New York: Guilford Press.</mixed-citation>
</ref>
<ref id="pone.0099912-Prochaska1"><label>42</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Prochaska</surname><given-names>JO</given-names></name>, <name name-style="western"><surname>Velicer</surname><given-names>WF</given-names></name> (<year>1997</year>) <article-title>The transtheoretical model of health behavior change</article-title>. <source>Am J Health Promot</source> <volume>12</volume>: <fpage>38</fpage>–<lpage>48</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Kalden1"><label>43</label>
<mixed-citation publication-type="other" xlink:type="simple">Kalden R, Caroll K, Donovan D, Cooney N, Monti P, et al. (1992) Cognitive behavioral Coping Skills Therapy Manual: A Clinical Research Guide for Therapists Treating Individuals With Alcohol Abuse and Dependence. In: Mattson MEM, editors. NIAAA Project MATCH Monograph Series. Rockville, Md: National Institute on Alcoholism and Alcohol Abuse.</mixed-citation>
</ref>
<ref id="pone.0099912-Chan1"><label>44</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Chan</surname><given-names>KK</given-names></name>, <name name-style="western"><surname>Neighbors</surname><given-names>C</given-names></name>, <name name-style="western"><surname>Gilson</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Larimer</surname><given-names>ME</given-names></name>, <name name-style="western"><surname>Alan</surname><given-names>MG</given-names></name> (<year>2007</year>) <article-title>Epidemiological trends in drinking by age and gender: providing normative feedback to adults</article-title>. <source>Addict Behav</source> <volume>32</volume>: <fpage>967</fpage>–<lpage>976</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Cohen1"><label>45</label>
<mixed-citation publication-type="other" xlink:type="simple">Cohen J (1997) Statistical power analyses for the behavioral sciences (revised ed.). New York: Academic Press.</mixed-citation>
</ref>
<ref id="pone.0099912-Borenstein1"><label>46</label>
<mixed-citation publication-type="other" xlink:type="simple">Borenstein M, Hedges L, Higgins JPT, Rothstein HR (2009) Introduction to meta-analysis. Chichester, UK: Wiley.</mixed-citation>
</ref>
<ref id="pone.0099912-Higgins2"><label>47</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Higgins</surname><given-names>JP</given-names></name>, <name name-style="western"><surname>Thompson</surname><given-names>SG</given-names></name>, <name name-style="western"><surname>Deeks</surname><given-names>JJ</given-names></name>, <name name-style="western"><surname>Altman</surname><given-names>DG</given-names></name> (<year>2003</year>) <article-title>Measuring inconsistency in meta-analyses</article-title>. <source>BMJ</source> <volume>327</volume>: <fpage>557</fpage>–<lpage>560</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Ioannidis1"><label>48</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Ioannidis</surname><given-names>JP</given-names></name>, <name name-style="western"><surname>Patsopoulos</surname><given-names>NA</given-names></name>, <name name-style="western"><surname>Evangelou</surname><given-names>E</given-names></name> (<year>2007</year>) <article-title>Uncertainty in heterogeneity estimates in meta-analyses</article-title>. <source>BMJ</source> <volume>335</volume>: <fpage>914</fpage>–<lpage>916</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Orsini1"><label>49</label>
<mixed-citation publication-type="other" xlink:type="simple">Orsini N, Bottai M, Higgins JP, Buchan I (2006) Heterogi: Stata module to quantify heterogeneity in a meta-analysis. [Computer Software].</mixed-citation>
</ref>
<ref id="pone.0099912-Kraemer1"><label>50</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Kraemer</surname><given-names>HC</given-names></name>, <name name-style="western"><surname>Kupfer</surname><given-names>DJ</given-names></name> (<year>2006</year>) <article-title>Size of treatment effects and their importance to clinical research and practice</article-title>. <source>Biol Psychiatry</source> <volume>59</volume>: <fpage>990</fpage>–<lpage>996</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Riper3"><label>51</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Riper</surname><given-names>H</given-names></name>, <name name-style="western"><surname>van Straten</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Keuken</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Smit</surname><given-names>F</given-names></name>, <name name-style="western"><surname>Schippers</surname><given-names>G</given-names></name>, <etal>et al</etal>. (<year>2009</year>) <article-title>Curbing problem drinking with personalized-feedback interventions: a meta-analysis</article-title>. <source>Am J Prev Med</source> <volume>36</volume>: <fpage>247</fpage>–<lpage>255</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Egger1"><label>52</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Egger</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Davey</surname><given-names>SG</given-names></name>, <name name-style="western"><surname>Schneider</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Minder</surname><given-names>C</given-names></name> (<year>1997</year>) <article-title>Bias in meta-analysis detected by a simple, graphical test</article-title>. <source>BMJ</source> <volume>315</volume>: <fpage>629</fpage>–<lpage>634</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Duval1"><label>53</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Duval</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Tweedie</surname><given-names>R</given-names></name> (<year>2000</year>) <article-title>Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis</article-title>. <source>Biometrics</source> <volume>56</volume>: <fpage>455</fpage>–<lpage>463</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Moher1"><label>54</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Moher</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Liberati</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Tetzlaff</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Altman</surname><given-names>DG</given-names></name> (<year>2010</year>) <article-title>Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement</article-title>. <source>Int J Surg</source> <volume>8</volume>: <fpage>336</fpage>–<lpage>341</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Saunders2"><label>55</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Saunders</surname><given-names>JB</given-names></name>, <name name-style="western"><surname>Aasland</surname><given-names>OG</given-names></name>, <name name-style="western"><surname>Babor</surname><given-names>TF</given-names></name>, <name name-style="western"><surname>Defuentes-Merillas</surname><given-names>L</given-names></name>, <name name-style="western"><surname>Grant</surname><given-names>M</given-names></name> (<year>1993</year>) <article-title>Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption II</article-title>. <source>Addiction</source> <volume>88</volume>: <fpage>791</fpage>–<lpage>804</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Hodgson1"><label>56</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Hodgson</surname><given-names>R</given-names></name>, <name name-style="western"><surname>Alwyn</surname><given-names>T</given-names></name>, <name name-style="western"><surname>John</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Thom</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Smith</surname><given-names>A</given-names></name> (<year>2002</year>) <article-title>The FAST Alcohol Screening Test</article-title>. <source>Alcohol Alcohol</source> <volume>37</volume>: <fpage>61</fpage>–<lpage>66</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Doumas1"><label>57</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Doumas</surname><given-names>DM</given-names></name>, <name name-style="western"><surname>Hannah</surname><given-names>E</given-names></name> (<year>2008</year>) <article-title>Preventing high-risk drinking in youth in the workplace: a web-based normative feedback program</article-title>. <source>J Subst Abuse Treat</source> <volume>34</volume>: <fpage>263</fpage>–<lpage>271</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Pemberton1"><label>58</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Pemberton</surname><given-names>MR</given-names></name>, <name name-style="western"><surname>Williams</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Herman-Stahl</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Calvin</surname><given-names>SL</given-names></name>, <name name-style="western"><surname>Bradshaw</surname><given-names>MR</given-names></name>, <etal>et al</etal>. (<year>2011</year>) <article-title>Evaluation of two web-based alcohol interventions in the U.S. military</article-title>. <source>J Stud Alcohol Drugs</source> <volume>72</volume>: <fpage>480</fpage>–<lpage>489</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Bischof1"><label>59</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Bischof</surname><given-names>G</given-names></name>, <name name-style="western"><surname>Grothues</surname><given-names>JM</given-names></name>, <name name-style="western"><surname>Reinhardt</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Meyer</surname><given-names>C</given-names></name>, <name name-style="western"><surname>John</surname><given-names>U</given-names></name>, <etal>et al</etal>. (<year>2008</year>) <article-title>Evaluation of a telephone-based stepped care intervention for alcohol-related disorders: a randomized controlled trial</article-title>. <source>Drug Alcohol Depend</source> <volume>93</volume>: <fpage>244</fpage>–<lpage>251</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Hansen1"><label>60</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Hansen</surname><given-names>AB</given-names></name>, <name name-style="western"><surname>Becker</surname><given-names>U</given-names></name>, <name name-style="western"><surname>Nielsen</surname><given-names>AS</given-names></name>, <name name-style="western"><surname>Gronbaek</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Tolstrup</surname><given-names>JS</given-names></name>, <etal>et al</etal>. (<year>2012</year>) <article-title>Internet-based brief personalized feedback intervention in a non-treatment-seeking population of adult heavy drinkers: a randomized controlled trial</article-title>. <source>J Med Internet Res</source> <volume>14</volume>: <fpage>e98</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Schulz1"><label>61</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Schulz</surname><given-names>DN</given-names></name>, <name name-style="western"><surname>Candel</surname><given-names>MJ</given-names></name>, <name name-style="western"><surname>Kremers</surname><given-names>SP</given-names></name>, <name name-style="western"><surname>Reinwand</surname><given-names>DA</given-names></name>, <name name-style="western"><surname>Jander</surname><given-names>A</given-names></name>, <etal>et al</etal>. (<year>2013</year>) <article-title>Effects of a web-based tailored intervention to reduce alcohol consumption in adults: randomized controlled trial</article-title>. <source>J Med Internet Res</source> <volume>15</volume>: <fpage>e206</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Suffoletto1"><label>62</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Suffoletto</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Callaway</surname><given-names>C</given-names></name>, <name name-style="western"><surname>Kristan</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Kraemer</surname><given-names>K</given-names></name>, <name name-style="western"><surname>Clark</surname><given-names>DB</given-names></name> (<year>2012</year>) <article-title>Text-message-based drinking assessments and brief interventions for young adults discharged from the emergency department</article-title>. <source>Alcohol Clin Exp Res</source> <volume>36</volume>: <fpage>552</fpage>–<lpage>560</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Boon1"><label>63</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Boon</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Risselada</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Huiberts</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Riper</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Smit</surname><given-names>F</given-names></name> (<year>2011</year>) <article-title>Curbing alcohol use in male adults through computer generated personalized advice: randomized controlled trial</article-title>. <source>J Med Internet</source> <volume>Res</volume> (<issue>13(2)</issue>) <fpage>e43</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Boon2"><label>64</label>
<mixed-citation publication-type="other" xlink:type="simple">Boon B, Huibers A (2006) Preventie problematisch alcoholgebruik. In: Meijer SA, Smit F, Schoemaker CG, Cuijpers P, editors. Gezond verstand. Evidence-based preventie van psychische stoornissen [Common sense. Evidence-based prevention of mental disorders]. VTV Themarapport (RIVM-rapportnummer: 270061003. Bilthoven: RIVM.</mixed-citation>
</ref>
<ref id="pone.0099912-Riper4"><label>65</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Riper</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Kramer</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Smit</surname><given-names>F</given-names></name>, <name name-style="western"><surname>Conijn</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Schippers</surname><given-names>G</given-names></name>, <etal>et al</etal>. (<year>2008</year>) <article-title>Web-based self-help for problem drinkers: a pragmatic randomized trial</article-title>. <source>Addiction</source> <volume>103</volume>: <fpage>218</fpage>–<lpage>227</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Wallace1"><label>66</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Wallace</surname><given-names>P</given-names></name>, <name name-style="western"><surname>Murray</surname><given-names>E</given-names></name>, <name name-style="western"><surname>McCambridge</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Khadjesari</surname><given-names>Z</given-names></name>, <name name-style="western"><surname>White</surname><given-names>IR</given-names></name>, <etal>et al</etal>. (<year>2011</year>) <article-title>On-line randomized controlled trial of an internet based psychologically enhanced intervention for people with hazardous alcohol consumption</article-title>. <source>PLoS One</source> <volume>6</volume>: <fpage>e14740</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-ODonnell1"><label>67</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>O’Donnell</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Anderson</surname><given-names>P</given-names></name>, <name name-style="western"><surname>Newbury-Birch</surname><given-names>D</given-names></name>, <name name-style="western"><surname>Schulte</surname><given-names>B</given-names></name>, <name name-style="western"><surname>Schmidt</surname><given-names>C</given-names></name>, <etal>et al</etal>. (<year>2014</year>) <article-title>The impact of brief alcohol interventions in primary healthcare: a systematic review of reviews</article-title>. <source>Alcohol Alcohol</source> <volume>49</volume>: <fpage>66</fpage>–<lpage>78</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Moyer2"><label>68</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Moyer</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Finney</surname><given-names>JW</given-names></name>, <name name-style="western"><surname>Swearingen</surname><given-names>CE</given-names></name>, <name name-style="western"><surname>Vergun</surname><given-names>P</given-names></name> (<year>2002</year>) <article-title>Brief interventions for alcohol problems: a meta-analytic review of controlled investigations in treatment-seeking and non-treatment-seeking populations</article-title>. <source>Addiction</source> <volume>97</volume>: <fpage>279</fpage>–<lpage>292</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Apodaca1"><label>69</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Apodaca</surname><given-names>TR</given-names></name>, <name name-style="western"><surname>Miller</surname><given-names>WR</given-names></name> (<year>2003</year>) <article-title>A meta-analysis of the effectiveness of bibliotherapy for alcohol problems</article-title>. <source>J Clin Psychol</source> <volume>59</volume>: <fpage>289</fpage>–<lpage>304</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Vasilaki1"><label>70</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Vasilaki</surname><given-names>EI</given-names></name>, <name name-style="western"><surname>Hosier</surname><given-names>SG</given-names></name>, <name name-style="western"><surname>Cox</surname><given-names>WM</given-names></name> (<year>2006</year>) <article-title>The efficacy of motivational interviewing as a brief intervention for excessive drinking: a meta-analytic review</article-title>. <source>Alcohol Alcohol</source> <volume>41</volume>: <fpage>328</fpage>–<lpage>335</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Burke1"><label>71</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Burke</surname><given-names>BL</given-names></name>, <name name-style="western"><surname>Arkowitz</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Menchola</surname><given-names>M</given-names></name> (<year>2003</year>) <article-title>The efficacy of motivational interviewing: a meta-analysis of controlled clinical trials</article-title>. <source>J Consult Clin Psychol</source> <volume>71</volume>: <fpage>843</fpage>–<lpage>861</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Cuijpers3"><label>72</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Cuijpers</surname><given-names>P</given-names></name>, <name name-style="western"><surname>Riper</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Lemmers</surname><given-names>L</given-names></name> (<year>2004</year>) <article-title>The effects on mortality of brief interventions for problem drinking: a meta-analysis</article-title>. <source>Addiction</source> <volume>99</volume>: <fpage>839</fpage>–<lpage>845</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Cunningham3"><label>73</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Cunningham</surname><given-names>JA</given-names></name>, <name name-style="western"><surname>Kypri</surname><given-names>K</given-names></name>, <name name-style="western"><surname>McCambridge</surname><given-names>J</given-names></name> (<year>2013</year>) <article-title>Exploratory randomized controlled trial evaluating the impact of a waiting list control design</article-title>. <source>BMC Med Res Methodol</source> <volume>13</volume>: <fpage>150</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Donker1"><label>74</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Donker</surname><given-names>T</given-names></name>, <name name-style="western"><surname>van</surname><given-names>SA</given-names></name>, <name name-style="western"><surname>Riper</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Marks</surname><given-names>I</given-names></name>, <name name-style="western"><surname>Andersson</surname><given-names>G</given-names></name>, <etal>et al</etal>. (<year>2009</year>) <article-title>Implementation of Internet-based preventive interventions for depression and anxiety: role of support? The design of a randomized controlled trial</article-title>. <source>Trials</source> <volume>10</volume>: <fpage>59</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Moyer3"><label>75</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Moyer</surname><given-names>VA</given-names></name> (<year>2013</year>) <article-title>Screening and behavioral counseling interventions in primary care to reduce alcohol misuse: U.S. preventive services task force recommendation statement</article-title>. <source>Ann Intern Med</source> <volume>159</volume>: <fpage>210</fpage>–<lpage>218</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Kaner2"><label>76</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Kaner</surname><given-names>E</given-names></name>, <name name-style="western"><surname>Bland</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Cassidy</surname><given-names>P</given-names></name>, <name name-style="western"><surname>Coulton</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Dale</surname><given-names>V</given-names></name>, <etal>et al</etal>. (<year>2013</year>) <article-title>Effectiveness of screening and brief alcohol intervention in primary care (SIPS trial): pragmatic cluster randomised controlled trial</article-title>. <source>BMJ</source> <volume>346</volume>: <fpage>e8501</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Cunningham4"><label>77</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Cunningham</surname><given-names>JA</given-names></name>, <name name-style="western"><surname>Khadjesari</surname><given-names>Z</given-names></name>, <name name-style="western"><surname>Bewick</surname><given-names>BM</given-names></name>, <name name-style="western"><surname>Riper</surname><given-names>H</given-names></name> (<year>2010</year>) <article-title>Internet-based interventions for problem drinkers: From efficacy trials to implementation</article-title>. <source>Drug Alcohol Rev</source> <volume>29</volume>: <fpage>617</fpage>–<lpage>622</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Riper5"><label>78</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Riper</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Kramer</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Keuken</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Smit</surname><given-names>F</given-names></name>, <name name-style="western"><surname>Schippers</surname><given-names>G</given-names></name>, <etal>et al</etal>. (<year>2008</year>) <article-title>Predicting successful treatment outcome of web-based self-help for problem drinkers: secondary analysis from a randomized controlled trial</article-title>. <source>J Med Internet Res</source> <volume>10</volume>: <fpage>e46</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Robinson1"><label>79</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Robinson</surname><given-names>SM</given-names></name>, <name name-style="western"><surname>Sobell</surname><given-names>LC</given-names></name>, <name name-style="western"><surname>Sobell</surname><given-names>MB</given-names></name>, <name name-style="western"><surname>Arcidiacono</surname><given-names>S</given-names></name>, <name name-style="western"><surname>Tzall</surname><given-names>D</given-names></name> (<year>2014</year>) <article-title>Alcohol and drug treatment outcome studies: new methodological review (2005–2010) and comparison with past reviews</article-title>. <source>Addict Behav</source> <volume>39</volume>: <fpage>39</fpage>–<lpage>47</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Saitz1"><label>80</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Saitz</surname><given-names>R</given-names></name> (<year>2010</year>) <article-title>Alcohol screening and brief intervention in primary care: Absence of evidence for efficacy in people with dependence or very heavy drinking</article-title>. <source>Drug Alcohol Rev</source> <volume>29</volume>: <fpage>631</fpage>–<lpage>640</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Eysenbach1"><label>81</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Eysenbach</surname><given-names>G</given-names></name> (<year>2005</year>) <article-title>The law of attrition</article-title>. <source>J Med Internet Res</source> <volume>7</volume>: <fpage>e11</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Postel2"><label>82</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Postel</surname><given-names>MG</given-names></name>, <name name-style="western"><surname>de Haan</surname><given-names>HA</given-names></name>, <name name-style="western"><surname>ter Huurne</surname><given-names>ED</given-names></name>, <name name-style="western"><surname>van der Palen</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Becker</surname><given-names>ES</given-names></name>, <etal>et al</etal>. (<year>2011</year>) <article-title>Attrition in web-based treatment for problem drinkers</article-title>. <source>J Med Internet Res</source> <volume>13</volume>: <fpage>e117</fpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-McCambridge1"><label>83</label>
<mixed-citation publication-type="other" xlink:type="simple">McCambridge J, Kypri K, McElduff P (2013) Regression to the mean and alcohol consumption: A cohort study exploring implications for the interpretation of change in control groups in brief intervention trials. Drug Alcohol Depend.</mixed-citation>
</ref>
<ref id="pone.0099912-McCambridge2"><label>84</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>McCambridge</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Kypri</surname><given-names>K</given-names></name>, <name name-style="western"><surname>McElduff</surname><given-names>P</given-names></name> (<year>2014</year>) <article-title>Regression to the mean and alcohol consumption: a cohort study exploring implications for the interpretation of change in control groups in brief intervention trials</article-title>. <source>Drug Alcohol Depend</source> <volume>135</volume>: <fpage>156</fpage>–<lpage>159</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Roerecke1"><label>85</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Roerecke</surname><given-names>M</given-names></name>, <name name-style="western"><surname>Gual</surname><given-names>A</given-names></name>, <name name-style="western"><surname>Rehm</surname><given-names>J</given-names></name> (<year>2013</year>) <article-title>Reduction of alcohol consumption and subsequent mortality in alcohol use disorders: systematic review and meta-analyses</article-title>. <source>J Clin Psychiatry</source> <volume>74</volume>: <fpage>e1181</fpage>–<lpage>e1189</lpage>.</mixed-citation>
</ref>
<ref id="pone.0099912-Smit1"><label>86</label>
<mixed-citation publication-type="journal" xlink:type="simple"><name name-style="western"><surname>Smit</surname><given-names>F</given-names></name>, <name name-style="western"><surname>Lokkerbol</surname><given-names>J</given-names></name>, <name name-style="western"><surname>Riper</surname><given-names>H</given-names></name>, <name name-style="western"><surname>Majo</surname><given-names>MC</given-names></name>, <name name-style="western"><surname>Boon</surname><given-names>B</given-names></name>, <etal>et al</etal>. (<year>2011</year>) <article-title>Modeling the cost-effectiveness of health care systems for alcohol use disorders: how implementation of eHealth interventions improves cost-effectiveness</article-title>. <source>J Med Internet Res</source> <volume>13</volume>: <fpage>e56</fpage>.</mixed-citation>
</ref>
</ref-list></back>
</article>