#HEORInsights

The most recent evidence shows patient recruitment and retention issues to be a persistent problem in clinical trials. Also, it is almost certain that this problem will only continue to grow as the years go on. (1,2) Missing data is often due to patients being lost to follow-up or withdrawing before data collection time points, difficulties in measuring and recording outcomes for patients who are retained, incomplete or missing patient reported outcomes (PRO), or exclusion of data from randomized patients from the analysis population. Loss of participants during trial follow-up leads to bias, thus reducing power that affects the generalizability, validity and reliability of results. While losses fewer than 5% may lead to minimum bias, 20% loss can threaten trial validity. (3,4)

Findings from a recent Delphi survey showed that identifying methods to improve recruitment was a top methodological research priority, whereas methods to minimize attrition and the development of core outcome sets came second. (5) These priorities are set with an aim to minimize waste in research, ensuring robust and cost-effective trials. This can primarily achieved by maximizing the retention of all recruited patients in the study as well as the collection, analysis and reporting of a complete set of outcomes. (6)

Insufficient recruitment considerably impacts the scientific and financial viability of an RCT. The possibility of leading to a type 2 error (incorrect conclusion, with no significant difference between treatment groups) increases if the estimated sample size target is not met. Sufficient patient enrolment accounts for a base for projected retention of patients, which further helps in evaluation of patient data, thereby resulting in extension of trial period and increase in the study cost. This may lead to a level of uncertainty about the treatment efficacy, while also resulting in delay for a potentially effective therapy. Slowly gathering trial evidence may impact the financial investment of the funding agency, thus making a way for lesser reliability but more rapid approach to evaluation. (1,4)

For effective conduct of RCTs, the barriers to recruitment must be identified and potential strategies should be devised to improve the same in clinical trials. Consequently, trial researchers assume various strategies for improving patient retention and generating maximum data return or compliance to follow-up procedures. These strategies are often implemented to motivate and keep participants or site clinicians engaged in a trial. Few global studies determining the retention-related issues suggest strategies, such as piloting the recruitment process, financial and educational incentives for clinicians as well as patients, newsletters and reminders for patients, open- versus placebo-controlled trials, assistance with patient travel, and networking with various healthcare professionals. (7,8)

Some trial researchers have opined for increasing retention in trials. One such suggestion is good monitoring process for data collection in order to identify and address any problem that might facilitate retention, e.g. telephonic reminders. Training and working with local research site staff to minimize missing data is strongly recommended. (8)

Additionally, one of the oldest and largest problems faced by patient recruitment is the extent of awareness among general public about clinical trials. Thus, the more aware clinical trial patients are about the study, the more inclination they show towards signing up for it. It’s ethically wrong to directly encourage a patient to commit to a clinical trial, which is why the emphasis should be on education and not persuasion. Also, just the basic information has been shown to increase the likelihood of participation. Furthermore, doctors can play an important role in generating awareness, as they are at the front line of care and are trusted to provide the best care possible, which clinical trials often represent. Moreover, a common practice by the pharmaceutical industry to educate as many people as possible, by casting a broad net, would also help increasing the patient retention. (8,9)

The common cure for retention challenges is interaction with patients. The buzzword that is making rounds throughout the industry since last few years, when it comes to underlining patient communication and comfort, is ‘patient centricity’. It’s a contested term as to its actual application, but it implies for whatever method successfully involves the patient to a greater extent within the trial. (9)

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References 

1. Kadam RA, et al. Challenges in recruitment and retention of clinical trial subjects. Perspectives in Clinical Research 2016; 7(3):137-143.
2. Toerien M, et al. A review of reporting of participant recruitment and retention in RCTs in six major journals. Trials 2009; 10:52.
3. Dettori JR. Loss to follow-up. Evidence-Based Spine-Care Journal 2011; 2(1):7-10.
4. Kearney A, et al. Identifying research priorities for effective retention strategies in clinical trials. Trials 2017; 18:406.
5. Tudur Smith C, et al. The trials methodological research agenda: results from a priority setting exercise. Trials 2014; 15(1):32.
6. Salman RA-S, et al. Increasing value and reducing waste in biomedical research regulation and management. Lancet 2014; 383(9912):176–85.
7. Robinson KA, et al. Systematic review identifies number of strategies important for retaining study participants. J Clin Epidemiol 2007; 60:757.
8. Brueton VC, et al. Strategies to improve retention in randomized trials: a Cochrane systematic review and meta-analysis. BMJ Open 2014; 4:e003821.
9. Clinical trials and their patients: The rising costs and how to stem the loss. Pharmafile, 2016.