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.

Electronic Medical Records Utility in Clinical Trial Conduct

Patient dropouts and those lost to follow-up (LTFU) pose a major challenge and costly burden in the conduct of clinical trials as each patient represents a valuable source of data.  High patient dropout rates are not only costly but pose a risk to the interpretation and validity of intended research findings.  Therefore, retention and adherence processes are critical so patients don’t dropout and become lost to follow-up (LTFU).

Such procedures require a combination of patient, physician, and coordinator related factors including recruiting patients per protocol inclusion criteria, managing patient expectations, and efficient recording of all relevant documentation.  These are important factors that can favorably influence cost effectiveness.  In this regard, electronic medical records ( EMRs ), considered an asset to the health care industry, offer much advantage to clinical research by assisting in recruiting the correct patients to the appropriate clinical trial, ¹ aiding in cost effective subject recruitment, and rapidly identifying adverse events.^{2, 3} These factors can reduce patient dropout rates and patients LTFU.  Additionally, EMRs facilitate clinical investigators in maintaining adequate and accurate patient case histories and in providing direct access to source data/documentations for trial-related monitoring required by the FDA,⁴ GCP guideline and ICH Guideline for Good Clinical Practice (E6).⁵   Such formation may also provide the necessary information to find a patient LTFU and reintegrate them into the study.

Despite the many advantages of EMRs, there are some potential concerns with their utilization based on data integrity assurance and privacy mandates per the Health Insurance Portability and Private Act (HIPAA) ^6,7 for Sponsors of clinical research due to the necessitation of monitors and quality assurance auditors to inspect study records.  However, as the HIPAA privacy rule requires that an individual participating in research provide signed permission before records may be accessed by researchers and/or due to FDA-required elements, ⁸ these concerns can be easily avoided if the informed consent process is conducted as appropriate, which includes an adequately prepared informed consent form (ICF) that is signed by the patient prior to any research related activity. Therefore, if a valid informed consent process is in place, the monitoring of any medical record, including EMRs, even if the EMR is part of a larger record that includes non-research related health information is considered HIPAA complaint.

Importantly, it must be recognized that while Electronic Medical Records (EMR) can greatly enhance the entire clinical trial process and subsequently increase patient retention, reduce dropout rates and patients LTFU, there must be quality monitoring data and recordkeeping systems and standard operating procedures that sponsors have in place  to assure data integrity and patient privacy per governing mandates.

1. J.W. Goldwein et al., Abstract No. 6626, Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings, Part 1 Vol. 25, No. 18S (June 20 Supplement) 2007: 6626.

2. M. Mowry and D. Constantinou, “Electronic Health Records: A Magic Pill?” Applied Clinical Trials, February 2007.

3. J.C. Crosson et al, “Electronic Medical Records and Diabetes Quality of Care: Results From a Sample of Family Medicine Practices,” Annals of Family Medicine, 5: 209-215 (2007).

4. Code of Federal Regulations, Title 21, Part 312.62(b) (U.S. Government Printing Office, Washington, DC).

5. Food and Drug Administration, “ICH E6 Good Clinical Practice: Consolidated Guidance, Section 4.9.7, Federal Register 62 (90), 25691-25709 (May 1997).

6. U.S. Department of Health & Human Services, Health Insurance Portability and Privacy Act of 1996 (U.S. Government Printing Office, Washington, DC).

7. Code of Federal Regulations, Title 45, Parts 164-168 (U.S. Government Printing Office, Washington, DC).

8. Code of Federal Regulations, Title 21, Part 50 Section 25(a)(5) (U.S. Government Printing Office, Washington, DC).

Please contact our CEO David Betz at 888-965-6696, and he will answer any immediate questions you have and provide you information about our OmniTrace lost to follow-up patient search services.  You can also email David at:  dave@omnitrace.com.

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.

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.