As described above in the article published on January 26, 2022 on our business blog, Fogel DB has identified several factors associated with the failure of a clinical trial and opportunities for increasing its chances of being successful.
The inability to enrol and retain sufficient participants is another long-standing cause of trial failure. This is particularly true for cancer trials, as 20-25% of these clinical trials is reported to fail to enrol a sufficient number of patients and thus to complete. Too many dropouts in a clinical study may result in the trial becoming underpowered, and may force the study sponsor to increase allocated funds and the number of study sites in an effort to meet the minimum patient enrolment required to avoid the trial failure. To be prepared for any such event, the author recommends the development of contingency plans in advance, whenever feasible.
As stated by Fogel, “increasing the speed of enrolment leads to faster study completion, and may be associated with fewer dropouts, better statistical power, and increased confidence in results”.
The selection of study sites is an important aspect of the clinical trial process. A study site’s successful experience with previous clinical trials and nearby larger pool of potentially eligible patients are predictors of positive recruitment performance. Besides, patient enrolment and retention can be positively affected by enthusiasm, motivation and engagement of investigators and study staff, as well as incentives (e.g. fund provision for enrolling patients). Moreover, participant retention can be ameliorated by a dedicated recruiting/support staff at each study site and a study protocol tailored - as far as possible - to the site’s common clinical practice.
Fogel highlights that a clear and effective communication with the patient throughout a clinical trial is critical for patient recruitment, enrolment and retention. Indeed, as per a previous survey of several completed trials, patients who dropped out of a trial early were twice as likely to say that it was difficult to understand the informed consent form (ICF) than were patients who completed the trial (35% vs. 16%, respectively).
Addressing patients’ concerns and minimizing patients’ burden in designing and executing a clinical trial is also crucial to increase the likelihood of its success. Potential side effects from treatment(s), any additional examinations, uncertainty of study drug benefits and financial impacts (e.g. any out-of-pocket costs, loss of job support and work disruption) are among patients’ common concerns for participating in a clinical study.
The author suggests to take into account the following aspects to help minimize patients’ burdens:
- Easy-to-understand materials for patients
- A dedicated and enthusiastic principal investigator, as well as a supportive study staff
- An adaptive study schedule working in synergy with patient's constraints
- A trial management software to send effective reminders to patients via phone, text or email
- Awareness of the patient's presumable day-to-day experience during the study
Artificial Intelligence (AI) applications offer promise in helping selecting the most suitable study sites, improving patient recruitment (e.g. by facilitating the location of eligible patients and the enrolment of patients who are likely to complete the trial), reducing patients’ burdens (e.g. by minimizing travel and wait times and out-of-pocket expenses) and improving trial execution.
In conclusion, study design and eligibility criteria, study site selection and addressing patients’ concerns and burdens are major areas where clinical trial effectiveness can be positively affected.
PRINEOS provides sound support in designing and optimizing clinical studies, as well as interacting with KOLs and patient advocacy groups. Thus, our experts can help you to better conceive your study and improve patient recruitment and retention.
D.B. Fogel. Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: A review. Contemporary Clinical Trials Communications. 2018;11:156-164. DOI: 10.1016/j.conctc.2018.08.001