STUDY PUBLISHED IN BRITISH MEDICAL JOURNAL SHOWS THAT
PATIENTS ARE NOT COMPLIANT WITH CLINICAL TRIAL PROTOCOLS
Study raises serious doubts about the integrity of patient-reported data in clinical trials

SCOTTS VALLEY, CA (May 20, 2002) – A study just published in the British Medical Journal shows that subjects in clinical trials who are asked to make real-time written entries in a paper diary routinely fail to do so, undermining the validity of the patient self-report data collected in those studies.

Researchers have long suspected that subjects complete batches of paper diary cards rather than completing them in real-time as instructed. The resulting recall bias impacts the subjects’ ability to accurately report on their condition and reaction to medications, yielding data that is invalid or unreliable. In this study, 79% of paper diary entries were falsified, raising serious doubts about the validity of data collected from patients when using paper diaries in clinical practice and research.

The study, sponsored by the National Cancer Institute with in-kind support from invivodata, was designed to compare compliance between subjects using a paper diary and those using an electronic diary developed by invivodata, inc. The study was led by Drs. Arthur Stone and Saul Shiffman, pioneers in behavioral science methods for collecting patient data using Ecological Momentary Assessment (EMA). EMA encompasses methods for collecting valid and reliable patient self-report data in real time and in patients’ natural environment.

The National Cancer Institute study is the first to document subject compliance with paper diaries.Compliance with paper diaries has been hard to assess, because the time of diary completion is not objectively documented. What enabled this study to document compliance was the invention of an instrumented paper diary that electronically tracked diary use unobtrusively. Paper diary compliance rates were compared with those achieved using the invivodata electronic diary, which implements EMA principles.

Just as in many prior studies using paper diaries, the subjects in this study submitted most of the required diary pages – 90% of them, in fact – with what appeared to be legitimate times and dates. However, when the electronic records were checked, only 11% of the pages could have been filled
out as required by the study protocol. In contrast, subjects using the invivodata electronic diaries completed 94% of their entries on time, as verified by the electronic records. The study authors note that the timely reporting achieved by the invivodata system is key to the validity and integrity of the data.

Patient diaries are commonly used in pharmaceutical trials. DataEdge has estimated that 25% of all clinical trials for pharmaceutical products use a patient diary. The companies that sponsor these trials stand to benefit from improved integrity of patient self-report data. “Data integrity in patient self-report is critical to our research,” commented R. Michael Gendreau, M.D., Chief Medical Officer at Cypress Bioscience, Inc. “In our clinical studies, the invivodata diary has helped us capture real-time data from patients in their natural environment that was more sensitive to change than data collected during routine visits to the research site. We have observed high rates of patient acceptance and compliance with the electronic diary in our protocols, and the invivodata
patient management system helped produce significantly better data than we could have ever collected using paper diaries.”

“Patients want to provide data that will help researchers find cures,” commented Saul Shiffman, Ph.D., co-founder and Chief Science Officer of invivodata. “Patients are the most important element of a clinical trial, yet the most difficult to manage. Old paper diary methods do not help the patients successfully comply with the study protocol. We have designed and perfected the invivodata system over the years to effectively promote compliance in the real world. The invivodata solution helps study sponsors gain a deeper, more accurate understanding of their new treatment by helping patients effectively communicate how they feel while in the study.”

In the group using paper diaries, none of the patients showed good compliance, and all showed evidence of back-filling entries after the fact. The paper diary binder was never opened even once on one-third of all study days, even though 90% of the diary cards for these days were turned in. This indicates that the study protocol was not followed and undermines the validity of the data. A large body of research shows that when people try to remember their experience, they introduce errors and bias into the data. This may be magnified when patients in clinical trials complete a batch of diaries after the fact, to make up for missed diary entries. The noise and bias introduced into the data in this way can threaten the validity of the clinical data, and undermine the ability of the study to document a drug’s effectiveness.

Clinical researchers, long aware of the value of accurate patient self-report, are recognizing the value of new methods for collecting reliable data from patients. “For an increasing number of studies, patient-reported data is a critical endpoint,” noted Ronald S. Waife, President of Waife & Associates, Inc., a leading clinical research consulting firm. “It has been clear for some time that only through the application of the right information technologies can the scientific validity of patient-reported data meet the clinical research needs. This new study should help validate proven electronic means of collecting patient-reported data, so that sponsors and regulatory bodies will endorse the shift away from discredited paper methods.”

The study publication can be accessed from the Web site of the British Medical Journal (www.bmj.org). Additional study details or information on the invivodata electronic diary solution can be obtained by visiting the invivodata website (www.invivodata.com) or by contacting invivodata (email: info@invivodata.com, tel: (831) 438-9550).

About invivodata

invivodata (www.invivodata.com) provides science-based electronic diary services for clinical trials. invivodata’s system uniquely combines behavioral science, technology, and clinical expertise to capture clinical trial data of the highest-possible integrity directly from patients. Far superior to paper diary methods, invivodata’s electronic patient diary solution, the invivosystem, delivers more reliable and valid data than any other diary method by driving patient compliance with the protocol and eliminating recall biases that plague self-report studies. The invivodata solution provides real-time access to study data, giving study researchers and sponsors visibility into study progress and improving study efficiencies. The invivosystem was developed and validated according to a rigorous Computer System Validation policy based on 21 CFR Part 11. It has been used in nearly 50 studies involving thousands of patients. Having collected more than 2,000,000 patient-initiated records, invivodata’s solution is mature and market-proven. No other electronic diary solution has
processed more patient records than the invivosystem. invivodata, inc., a privately-held company, is headquartered in Scotts Valley, California. The clinical trial operation center is located in Pittsburgh, Pennsylvania.

Editors note: for additional reading please see: "The Science of Patient Experience" By: Doug Engfer: President & CEO, invivodata