Burden of Patient Dropouts and Patients Lost-To-Follow-Up On Clinical Studies

By Dave Betz, Dana Betz and Diane Leahy – OmniTrace Corp.

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

What affects does poor patient retention have on clinical trials?

Patient dropout and those 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 dropout and LTFU rates in clinical trials are a major threat both to the ability to conduct critical research and to generalize results to broader populations.

What common causes have been identified that are associated with low retention rates?

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^1,2 

Additionally, dropouts occur when participants’ perceived time and effort invested outweigh the perceived benefits of being in a study.¹ Further, logistical issues identified include the timing of appointments with study staff, and the need for flexibility in times and dates available for meetings and data collection.^1,3  

Are there specific patient characteristics that have been shown to be associated with a higher dropout rate?

Several studies have investigated demographic characteristics of participants who tend to dropout and/or those LTFU of research protocols. One characteristic predictive of dropout appears to be age, with younger participants (< 50 years old) at significantly higher risk than older participants.⁴ It has also been reported that minorities represent higher dropout and LTFU rates.¹ In addition to demographic factors, psychological and behavioral characteristics appear to predict higher dropout risk and LTFU.¹          

What factors should be considered when designing the study that can compensate for dropouts and LTFU?

Dropout and/or LTFU rates are estimated to range from 15-40% of enrolled subjects depending on the therapeutic area, investigational drug, inclusion/exclusion criteria, and patient characteristics/demographics.⁵ Therefore, when designing a study all of these factors must be considered for estimating a potential dropout rate and then increasing the number of subjects enrolled, investigational sites, as well as the supplies and resources to compensate for respectively.⁵

How can patients’ retention be improved during conduct of clinical studies?

Retention and adherence depend on a combination of patient-, physician- and coordinator-related issues, factors that need to be carefully evaluated to ensure success.¹ Positive reinforcement and patient motivation driven by study health professionals and study personnel play a major role in a patient’s belief that the study is important and enhances a commitment to finish.¹   Importantly, strategies must use multiple methods and include initiatives that address multiple barriers and facilitators of research participation, such as motivation, convenience, and data tracking will enhance patient retention.

Who is Omnitrace and how can it assist drug manufacturers in risk management/PV approaches?

Omnitrace is a people locate company that has been in operation for 8 years.  Omnitrace has a stellar record of success in locating tens  of thousands of people worldwide servicing, several sectors including the pharmaceutical  /biotechnological industry in finding clinical trial patients dropout and those LTFU.  As mentioned, as every participant in clinical research is a valuable source of safety information, locating patients LTFU is critical to maintaining a robust risk management system.

References

1. 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.
2. 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.
3. 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.
4. 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.
5. Berger A, Neumark D.  Enhancing recruitment and retention in randomized clinical management.  Oncology Nursing Forum, 2007, 34, e18.