By Victor Muts, MD, PhD, Associate Project Director, Clinical Division, inVentiv Health Clinical
These days, the CROs and the study sponsors are trying hard to diminish the guesswork during the assessment of the subject recruitment rates at the study feasibility stage. They implement a plethora of strategies, virtual models, painstakingly going through the epidemiology data and even coming up with patient recruitment laws (e.g. Lasagna’s Law: “The incidence of patient availability sharply decreases when a clinical trial begins and returns to its original level as soon as the trial is completed”). Nevertheless, direct input from the potential investigators still plays a significant role in assessing patient recruitment rates in clinical studies. Unfortunately, in many instances, the input from the clinical sites proves to be overly optimistic midway through the study and many sponsors and CROs find themselves struggling for the subjects they need, wishing they would have taken investigators’ forecasts with a grain of salt when deciding how many sites they would need to run a successful study.
There are several reasons as to why the potential investigators may overestimate their recruitment potential during the study feasibility stage and at a qualification visit.
If the team spends enough time to thoroughly assess these issues early on in the study, the input from the potential investigators may prove to be much more reliable. In particular, the key potential investigators should play a role in the study protocol development (or at least reviewing it in detail). It is vital to receive the input from different investigators (geographical location/hospital type/experience in clinical trials) to get a well-balanced and thoughtful response. During the consideration of the potential protocol amendment, the team should make the effort to re-assess the impact on the recruitment rate (ideally, again interacting with the investigators as appropriate).
It would also be very beneficial to launch into a productive discussion of inclusion/exclusion criteria during the initial polling of investigators. Quite often, the potential PIs would just scroll through the criteria without giving them a serious thought, as it is not even guaranteed that the study will start one day – and even if it will, the site may never be included for various reasons. Obviously the investigator would expect the CRO/sponsor representative to be intimately familiar with the study protocol during the feasibility stage, up to a point of walking the doctor through the protocol on the phone or indeed, in person. In other words, efforts should be in place to have the qualification process productive and not just being a formal confirmation of the potential investigators “having this type of patients and being sufficiently interested in the study”.
Whenever assessing recruitment potential at a given site, it is also worthwhile to try and ask additional questions and not just follow a rigid script. In particular, it can be recommended to discuss in detail the resourcing issues the site was having in the past and how quickly they were resolved; also, how often the site was able to meet the recruitment targets for previous studies. Ideally, if the PI projects a given number of subjects to be included in the study, (s)he should already have specific patients in mind, and it might be fair to ask about these subjects’ profile, e.g. age group, previous exposure to clinical trials, etc, to verify whether the patients are immediately available in the pipeline, or if they are just “estimations”. It would also be ideal to talk with the actual treating physician(s) at a given site to understand the recruitment potential better rather than relying on anyone from the team to complete the questionnaire. All the time and effort spent at this stage pays back when the study is up and running.
Ultimately, the investigators should be clear that there are no penalties associated with under-promising and over-delivering; it is the other way round that hurts the clinical study, in extreme cases resulting in a promising drug never actually making it to the pharmacy.
Victor Muts, MD, PhD is an Associate Project Director, Clinical Division at inVentiv Health Clinical, working in the industry for over 15 years, with the primary area of specialization being neuroscience and rare diseases. He is based in Kyiv, Ukraine.