The Ethics Committee of the Medical Faculty of Essen University was consulted and a formal written waiver for the need of ethics approval was issued (13-5373-BO).

In 2010 the “Medication Plan” application was specified for iOS by the Department of Nephrology, Essen University Hospital, Essen, Germany, in cooperation with the companies DigitalOffice (Dortmund, Germany), Bergisch Media (Heiligenhaus, Germany) and Digitalpocket (Bochum, Germany) and the support of the German Society of Nephrology. “Medication Plan” is a native smartphone application, which allows users to maintain and alter a drug therapy plan on their personal device (fig. 1). An online drug database customized by the Department of Nephrology at Essen University Hospital, facilitates the entries. Users may specify intake requirements according to the medication regimen issued by the prescribing physician and the patients' own personal needs (e.g. how long to take the medication, medication dosage, whether to take on an empty stomach, how often to take, and at what time). A memory function and local push-notification alert remind users to take their medications at the pre-specified time. No permanent Internet connection is necessary and all data is stored locally on the device itself, reducing the possibility of erroneous transmission of personal health information. Users can enter vital sign data, and trends are presented graphically. If required, data can then be attached as csv-files and e-mailed to third parties.

The application was released first as a 1.0 version in the German-language App Store™ by Apple™ on December 14, 2010 and was available for download free of charge (http://itunes.apple.com/de/app/inephro-medikamentenplan/id405270576?mt=8 #). The application was actively advertised by the German Society of Nephrology (DGfN) by press releases and on its website (http://www.dgfn.eu/aktuell/inephro.html). This triggered a series of further articles in newspapers, television, patient self-help groups and blogs [10]–[15]. Interestingly after a positive article by a renowned consumer protection association (“Stiftung Warentest”) a significant increase of downloads could be detected [11]. Three additional updates were issued, which included enhancement of the medication specification requested by a large number of users, as well as the removal of software “bugs”. Prior to using the application a disclaimer as well as an agreement for a subsequent anonymous analysis of user data had to be consented by the user via activation of a hyperlink (implementation by QUEST objects GmbH, Tübingen). Additionally users were invited to voluntarily and anonymously fill in an online questionnaire, which had to be actively accessed by another hyperlink. The unique identifier numbers (UDID) of the respective iPhones were irreversibally encrypted by a MD5 message-digest algorithm (MD5-Hash). The activitiy of the encrypted UDID was then tracked (“creation”, “modification”, or “deletion” of drug information, as well as the “confirmation” of drug adherence within the application “Medication Plan”). Activity of the respective, encrypted UDID addresses and if available, associated demographic information were analysed using self-implemented software of Fraunhofer ISST, Dortmund, Germany, and GraphPad Prism version 6.0 for Macintosh, GraphPad Software, San Diego California U.S.A. Chi-square Test was performed by VassarStats (http://vassarstats.net/odds2×2.html). Data are presented as descriptive statistics and relative values were calculated using the corresponding sample.

The overall interest in the app of more than 11000 users was remarkable. However, download rates of other health-related apps, which targeted individuals with acute rather than chronic medical conditions have been reported to be much higher [7]. A software targeting chronically ill patients may at present only draw limited public interest, likely due to the epidemiological factors discussed below. Also, the application was published only in the German-language App Store™ by Apple™, which undoubtedly restricted its reach. Today there is still a threefold “digital divide” between age groups, sexes and according to education levels: Currently, the majority of German smartphone users are younger than 35 years although use in individuals older than 45 years is increasing steadily [16]. This is similarly reflected in the US trend of usage [17]. Compared with the average age of German smartphone users, the users of “Medication Plan” were older [16]. Two factors, likely, have contributed to this. Firstly it seems natural, since the prevalence of chronic diseases like hypertension or chronic ischemic heart disease grows with age [18]: In Germany 49% of women and 41% of men between 45 and 65 years declare to be suffering from chronic conditions [19]. More than half of the population are affected in the age cohort above 65 years [19]. Secondly, the German Society of Nephrology and several self-help groups actively advertised or reported on the application. This will probably have helped to draw the attention of older users. The fact that more than two thirds of our users were male illustrates the “digital divide” between the sexes. Women in general are still less interested in using the mobile Internet than men, as shown by surveys both from the German federal statistics institute and data from the US [5], [16]. In Germany at present especially older women use the mobile Internet significantly less than men [16]. A further schism exists between individuals with higher education and those with only basic qualifications. Among our users the proportion of university graduates was higher compared to the general population (28% vs. 13%) [20].

Regular use of the application decreased considerably within the first 2 months and lasted for more than a year only in a few cases. This finding is consistent with other studies citing a high attrition rate for internet interventions [21], which may be a reflection of an early interest in the novelty of the application, with a decline in eagerness as the newness of the intervention wears off. At present there is no scientific data on why people stop using mobile health applications. In a commercial survey by the Consumer Health Information Corporation (CHIC) on the use of healthcare apps in 2011 users reported "not user friendly" and "found a better one" as the most frequent reasons for no longer using an app (32% and 34% respectively). 26% of health apps were used only once after download. The drop out rate recorded in this survey was 74% (of 395 participants) by 10th use [22]. The fact that "Medication Plan" was not used permanently might therefore reflect deficits in usability and the necessity to continuously monitor customer/patients' demands. A criticism in usability might be that the app requires to set end dates for the medication. However, the aspect of an “unlimited therapy duration” was not raised in feedback mails. Others have found that most patients value interactive systems, i.e. devices that will give feedback - in this case on correct drug intake, a feature as yet not included in "Medication Plan" [23], [24]. Also, patients seem to prefer to use m-health in conjunction with visits to their doctors - another element which was not part of our study [23], [24]. In essence, use of this app can be seen as an expression of patients' wishes to improve the effectiveness of their treatment by improving their adherence. The most favourable - if speculative - explanation for the decline in use of "Medication Plan" is that it may only have been used temporarily as a "learning tool" at least by some patients: Once habituation to correct drug intake had been achieved, assistance may no longer have been regarded as necessary. Following this train of thought the fact that older individuals seemed to be using the app for a longer period than younger users may reflect a lesser slope in the learning curve of older users and the temporary adoption of the app as a "companion tool". Furthermore experiences from an “Ambient Assisted Living Project”, which is dedicated to the needs of an older group of users, report that the acceptance of 7-inch tablet PCs is very high [25]. In this context further studies should explore the possibilities of tablet computers for elderly and multimorbid users and patients' motivation for using an app like "Medication Plan". In summary, most of the users seem to have been “early adopters” of a new service: middle-aged male and - derived from the relatively small number of daily taken pills - comparatively healthy [26].