Original article
The use of handheld computers in clinical trials

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Abstract

A recently completed, randomized, double-blind placebo-controlled clinical trial is presented in which Palm handheld computers were used as a substitute for normal paper-based patient diaries. In this nasal provocation study, a common antihistamine approved for the treatment of seasonal allergic rhinitis was tested against placebo for evidence of additional properties. In addition to their medical examinations, the 12 study volunteers rated subjective complaints in a diary program on 4 examination days, for a duration of 4.5 hours every 15 minutes at each visit. This resulted in 903 data sets consisting of five questions each, or 4515 data points total. In this study the use of handheld computers resulted in an increase in data quality and shortened the time needed to close the database. Moreover, the benefit of electronic reminders for protocol compliance is clearly demonstrated. Our findings support the results found in the literature we reviewed. For more than 16 years, mobile computers have been supporting the implementation of clinical trials. Our review of 27 articles out of more than 100 clinical trials in which mobile computers have been used elaborates on the advantages and problems of this technology. We give a comprehensive overview of the various technologies as used in different settings, and then discuss the methodology of using mobile devices in comparison to traditional methods, the considerations that need to be made and things to be avoided in order to conduct a successful clinical trial with mobile tools. We conclude that mobile devices are very useful in most cases, especially when design and software validation aspects have been taken into account.

Introduction

Technology has been used to support clinical trials for many years. Databases and statistical software packages were the first technological aids to be utilized, followed by computers for on-site data entry. Thereafter, network solutions such as the French Minitel or the German BTX (Bildschirmtext) were employed. In the meantime, the Internet and especially the World Wide Web have increasingly been utilized in clinical trials as well as in many other fields of business and science 1, 2. Interestingly, a similar development can be observed with mobile devices. Nearly every mobile technology capable of data capture or data entry has and will be employed in clinical trials. A wide range of devices has been used, from the early programmable calculators and organizers to sophisticated pen-based devices with wireless data transmission capabilities 3, 4. We used Palm personal digital assistants instead of paper patient diaries in a randomized, placebo-controlled, double-blind clinical trial and describe here our methods and experience.

Section snippets

Objectives

A monocentric randomized two-phase cross-over study was carried out to verify whether Fexofenadine 120 mg tablets compared to placebo relieves nasal obstruction in subjects with a history of seasonal allergic rhinitis. In the following description of our experience with the handheld devices, we focus on data quality, patient acceptance, study settings, software validation, problems, and protocol compliance. The medical results are to be published elsewhere.

Setting and examinations

The study was approved by the local ethics committee. Twelve volunteers with a history of seasonal allergic rhinitis received Fexofenadine 120 mg once daily or placebo during a first period of 13 days. On the last day of that period immediately following drug intake, the volunteers underwent nasal provocation with their respective allergen. The same procedure had been carried out at baseline before drug intake. Thereafter, a washout period of 8 days followed. The volunteers were then crossed

Materials and methods

We used four different models of Palm handheld computers: PalmPilot (operating system: PalmOS 2.0, memory: 1 MB), Palm III (PalmOS 3.0, 2 MB), Palm IIIe (PalmOS 3.3, 2 MB) and Palm m100 (PalmOS 3.5.1, 2 MB). In spite of different operating system versions, the handling was identical for all models. Of the four keys for starting programs, the rightmost three were set to start ClinDiary; the default was not altered for the leftmost key, which starts the datebook application.

ClinDiary was

Results

During the test phase of ClinDiary before its first use in a study, two problems arose that could not be solved without altering the programming tools. First, changing data in the data entry screen in rapid succession resulted in a crash of the program. Second, activation of more than one answer per question was possible when using the pen very quickly, whereas the program design allows only one selection. These possible errors were accepted because the effort of optimizing the programming

Discussion

Mobile devices have been used in clinical trials for more than 16 years, utilizing different technologies (e.g., programmable calculators such as the Sharp PC-1500A) [3], devices built for special purposes such as the MEMS-4 Medication-Event Monitoring System [7] or the MiniDoc electronic patient diary 8, 9, 10, in-house developments such as PIPER (Prompting Intensity of Pain Electronic Recorder) [11] or Compu-Void [12], early pen-based devices such as the Go Corporation Prototype with the

Conclusions

The many years of experience using mobile computers in clinical trials have resulted in a few very important advantages besides those listed above: time, compliance, quality, and control. Time stamping of data and the use of reminders enhance the quality of the rendered data significantly. Several studies show that one cannot rely on the patient's memory and self-assessment, especially when real-time data gathering is essential 7, 42. The better the data exchange between examination centers,

Acknowledgements

The authors gratefully acknowledge linguistic support by Gena Kittel, B.A., in the preparation of this article. They acknowledge the efforts of Robert Matesic, Karin Funke, M.Sc., Peter Kiencke, Ph.D., Hartmut Stützer, Ph.D. and Kai Goetze for discussions and support with the score statistics.

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