Patient Dropouts / Lost To Follow-Up Implications

In any clinical trial, issues of patient retention, patient dropouts and patients lost to follow-up ( LTFU ) poses a major challenge.  Each patient represents a significant amount of time, effort and other resources, so that a high rate of patient dropouts are not only costly but pose a risk to the interpretation and validity of the intended research findings.

Patient dropouts / patients not retained of a study can quickly become lost to follow-up ( LTFU ), a critical situation where it is difficult to locate the patient and necessary patient information.  Retention and adherence depend on a combination of patient-, physician- and coordinator-related issues–factors that need to be carefully evaluated to ensure success.  Analyzing rates of patient dropouts and when they occur can give important information about patient characteristics, study design and conduct and respective intervention.  It is also important to assess the inclusion and exclusion criteria’s impact on patient dropout rates and the comparative losses between the control and intervention groups.

Patient dropouts and those lost to follow-up ( LTFU ) after recruitment negatively affects study duration, cost and generalizing the study results, which may result in regulatory approval delay.  In fact, it is widely recognized that high patient dropout and lost to follow-up ( LTFU ) rates in clinical trials are a major threat both to the ability to conduct critical research and to generalize results to broader populations.

Patient dropout and/or LTFU rates are estimated to range from 15-40% of enrolled subjects.  Therefore, while designing a study, an estimate of a potential patient dropout rate must be assumed and then compensated for by increasing the number of enrolled subjects, investigational sites, as well as the supplies and resources for these additions.¹ While this procedure is necessary, if judged incorrectly it becomes a costly burden.  For example, the average subject cost is estimated to be $6,500 per subject for a Phase II trial,  so if the trial design estimates an enrollment of 150 subjects but exceeds its enrollment by 10% to compensate for expected patient dropouts, it will cost an additional $97,500, not including the possible costs associated with delayed trial completion.²

Characteristics and Reasons for Patient Dropouts  and Lost To Follow-Up ( LTFU )

Several studies have investigated demographic characteristics of participants who tend to dropout and/or those LTFU of research protocols.  One characteristic predictive of patient dropout appears to be age, with younger participants (< 50 years old) at significantly higher risk than older participants.³  It has also been reported that minorities represent higher patient dropout and LTFU rates.⁴  In addition to demographic factors, psychological and behavioral characteristics appear to predict higher patient dropout risk and LTFU.⁴          

The causes for patients’ failure to complete the study have also been investigated and the most frequently cited reasons reflect issues related to competing life demands, logistical problems, demands of the study, and lack of motivation/commitment.  The most commonly cited explanations are stress related to family care responsibilities and interference with work^4,5  Lack of time, as well as complicated and cumbersome record-keeping and paperwork associated with a study have also been reported as common reasons.  A logistical barrier frequently cited is difficulty with transportation and inconvenience of study site location, including distance and parking.  Other logistical issues include the timing of appointments with study staff and the need for flexibility in times and dates available for meetings and data collection.^4,6  Positive reinforcement and patient motivation also play a major role in decisions concerning whether to complete or drop out of the study. 

Patient dropouts and LTFU occur when participants’ perceived time and effort invested outweigh the perceived benefits of being in a study.¹  Reasons patients give for completing research protocols also reflect incentive and motivation, and include remuneration, a commitment to finish, and a belief that the study is important.⁴  All of these factors that determine whether patients remain in studies or dropout and become LTFU obviously have implications for developing strategies that enhance the likelihood of study completion. Strategies must use multiple methods to enhance patient retention and include initiatives that address multiple barriers and facilitators of research participation, such as motivation, convenience, and data tracking.

We will discuss strategies that provide logistical approaches and initiatives to improve patient participation in our next post.

 References

• 1. Berger A, Neumark D. Enhancing recruitment and retention in randomized clinical management. Oncology Nursing Forum, 2007, 34, e18.
• 2. Blanton S, Morris D, Prettyman M, McCulloch K, Redond S, Light K, Wolf S. Lessons learned in participant recruitment and retention: The EXCITE trial. Physical Therapy, 2006, 86, 1520-1523.
• 3. Glasgow R, Nelson C, Kearney K, Reid R, Ritzwoller D, Strecher V, Couper M, Green B, Wildenhaus K. Reach, engagement, and retention in an Internet-based weight loss program in a multi-site randomized controlled trial. Journal of Medical Internet Research, 2007, 9, e11.
• 4. Janson S, Alioto M, Boushy H. Attrition and retention of ethnically diverse subjects in a multicenter randomized controlled research trial. Controlled Clinical Trials, 2001, 22, 236S-43S.
• 5. Parra-Medina D, Antonio A, Smith S, et al. Successful recruitment and retention strategies for a randomized weight management trial for people with diabetes living in rural, medically underserved counties of South Carolina: The POWER Study. Journal of the American Dietetic Association, 2004, 104, 70-75.
• 6. Tansey C, Matte A, Needham D, Herridge M. Review of retention strategies in longitudinal studies and application to follow-up of ICU survivors. Intensive Care Medicine, 2007, 33, 2051-2057.

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Please share your thoughts regarding our post on patient dropouts and patients lost to follow-up.  And, please do email or call us with any questions you have about our OmniTrace Corp. patient search and patient retention services:

dave@omnitrace.com (Dave Betz)
888-965-6696

THE CONTENT ON OUR OMNITRACE OWNED WEBSITES IS MERELY GENERAL INFORMATION OBTAINED BY ORDINARY PEOPLE AND NOT LEGAL ADVICE.  ONLY A QUALIFIED LAWYER CAN GIVE LEGAL ADVICE.  WE ARE NOT LAWYERS.