An observational registry study will recruit patients with a disease who are exposed to a drug of interest or a comparator drug. There are many comparator drugs on the market. The study size is planned for 1:1 or 1:2 ratios for the drug of interest vs comparator drugs. The protocol states recruiting two cohorts concurrently. However, recruiting comparator cohorts could be much faster. How do we cap the number of patients exposed to comparator drugs? How do we minimize the impact of capping on patient recruitment? Thanks.
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You do not indicate if this is a single or multiple site study.
In either case, it comes down to proactive communications. There needs to be one or more people responsible for monitoring the study enrollment in real time, which is easier if you are using some kind of EDC platform.
As you approach your enrollment limit for one arm or the other, that person or persons needs to be in proactive communication with the staff that are actively involved in approaching patients to participate in the study, so that the front line folks are aware that they are getting close to the limit. Ideally, you might also give them some projection of when to anticipate enrollment to close, but to stay actively recruiting until that occurs.
You also need to determine, in advance, what enrollment thresholds (note the plural) trigger those communications. You don’t want to just tell people that enrollment for one arm or the other is now closed with a single communication, without giving them advance notice as enrollment proceeds.
This is more complicated in the multi-site scenario, but you have to figure out how to organize and structure the communications so that the front line folks are not expending time and energy recruiting patients that can no longer actually be enrolled in the arm that hit the cap. You just get them and the prospective patients angry, if you don’t avoid this situation.
A key question becomes, what happens if there is a substantial lag in one arm or the other, such that your projection of completing enrollment in the slower arm might take too long, and extend your study timeline beyond what is tolerable. Consider what you will do if that occurs.
Obviously as an observational study, in the absence of prospective randomization to defined treatments, you need to consider the potential for various confounding factors, including patient selection bias and material baseline imbalance, when you compare your treatments and outcomes. You should consider enrolling, or at least attempting to enroll, a consecutive series of patients, that conform to your inclusion/exclusion criteria, with some ability to understand the characteristics of patients that were not willing to be participate, such as using a screening log. Consider what kind of multivariable modeling will make sense in this setting, as part of your analysis plan, and the potential limitations of your conclusions.
Also, if you are going to be using multiple comparators to the single treatment of interest, consider how that will impact your findings, which may include differentials in study dropouts, treatment compliance, adverse events, etc. within the comparator arm itself. You may want to consider how many comparators you will allow, and if there is a substantial difference in the utilization of any, do you exclude low volume treatments in your inclusion/exclusion criteria to avoid what may be low single digit outlier patients. That may be dependent upon how large your study is.
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I really appreciate your time replying to my post. It is a great pleasure to learn from you. It is a single site study. We will find out whether the site uses the EDC platform. We will also figure out how to organize and structure the communications as suggested. There are so many things that need to be considered. We will think more thoroughly to avoid some pitfalls in each and every step of the study. Thank you very much for sharing your thoughts.
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