One IS the Loneliest Number

Three Dog Night wasn’t singing about clinical research when they sang “One (is the Loneliest Number)," but just like love, one is the loneliest number in clinical research. Why? Because more often than not, you do not want to accrue only one participant to a clinical trial.

You may be reading this thinking that I’m wrong, your counterargument being that it is worse to accrue zero patients. However, I am here to propose that recruiting one subject is worse than no subjects at all.

When a study does not accrue anyone, it can close at any time. Staff can close the study out with the sponsor, conclude the study with the IRB, and move on to the next project. While not the best use of an institution’s resources, it is (hopefully) a short commitment with no long-term requirements. However, when one subject is enrolled, the study must remain open. The subject must complete the study treatment and required follow-up. Even after they are off-study, ongoing study requirements, such as survival follow-up and monitoring commitments are necessary, as well as the completion of regulatory requirements, such as protocol amendments, submission of IND reports and continuing reviews. This results in an investment of both monetary and human resources that could have been directed to a more productive study. If multiple studies only accrue one subject, it drains the resources of the clinical research enterprise.

It is unlikely that the study opened to only accrue one person, so additional time was dedicated to screening and recruiting patients that ultimately did not enroll in a trial because they do not exist or refuse to participate. This is demoralizing to the clinical research professional, as well as a drain of human resources that could be used to recruit to a successful protocol.

When multiple subjects are enrolled, there are economies of scale. The same forms, procedures, and physical resources (e.g. laboratory supplies) are utilized. Study staff is working within the protocol regularly. They know the requirements and procedures better. It is possible to assign several staff members to the protocol for coverage. It is likely that fewer compliance issues will occur, as the study is better known to the staff and investigators. This is not possible with a study that has only one subject. It is not prudent to assign multiple people to the protocol, or if multiple people are assigned, they have other assignments that split their attention with competing commitments and often lead to workplace stress and dissatisfaction.

However, as with most rules, there is an exception. Systematically designed case studies, known as “N of 1” studies, are of great value. These data-driven trials are still conducted under a protocol, with a specific order of procedures and requirements to be followed. They are another mechanism for studying precision, or individualized medicine. While not utilized often, these studies can provide incredibly helpful data when a larger, randomized controlled trial is not feasible (such as in the case of incredibly rare disease and/or a more common disease that refuses to react to regular clinical treatment).

Nevertheless, outside of the n=1 study design, my recommendation is that a study should not be allowed to enroll only one subject. If a study has been recruiting for a period of time and has no accrual, cut your losses and close the study. Do not wait for the opportunity for one subject to appear. While it may benefit the one subject in the short-term, the long-term result is that productive studies that can help numerous people at your institution cannot be conducted due to a lack of resources.

Wendy Tate, Director, Data Analytics, Forte Research Systems