CRI recently published a positive proof of concept study for an investigational antidepressant (Preskorn et al, Journal of Clinical Psychopharmacology, 2008). This study was unique in several ways. 

Most readers will likely agree that a positive study of an investigational antidepressant being conducted by a single site and involving only 15 participants on placebo and 15 on investigational drug is unique.

However, what also made this study unique and successful was that one site conducted the study and was provided the tools and the time needed to enroll the right study population. Parenthetically, the study was completed in a year.

The approach taken with this study was in stark contrast with the more conventional but often short sighted approach of pitting sites against each other to be high enrollers.

In my opinion, this competitive and compressed approach incentivizes and even pressures sites to err on the side of enrolling rather than excluding participants. That in turn can lead to a failed study and potentially a failed investigational medication.

In the study we recently completed, we knew that 260,000 people lived within an easy commute to our facility and were within the age range specified by the protocol.

Of these, we estimated that 5% of those 260,000 people should be suffering from major depression based on one year point prevalence numbers. That translates into 13,000 individuals.

To be eligible for the study, the participant had to have a history of non-response to at least one adequate trial of a serotonin selective reuptake inhibitor (SSRI).  Clinical trials typically find that 1 out of 3 depressed patients do not benefit from an adequate trial of an SSRI.   That means that 4,333 out of 13,000 (i.e., one out of three) potentially eligible subjects should meet this non-response entry criteria.

To enroll the needed subjects, a media campaign was conducted which reached this target population at least 100 times over 6 months. The campaign generated 1,292 phone calls and we phone screened all of these callers.

Out of these 1,292 callers, 192 (­i.e > 1 out of 6) passed our phone screen and came into our clinic for a face-to-face screen.  Of these 192, 47 individuals (i.e., >1 out of 4) met study eligibility criteria and went into the study.

We thus went from 1,292 callers to 47 participants. That illustrates the care and deliberation that went into this study. That, along with the remarkable efficacy of the investigational treatment is what, in my opinion, accounted for the study’s positive results.

The compressed and competitive enrollment approach is inconsistent with this level of care and deliberation in selecting participants.

Nevertheless, the compressed, competitive enrollment approach seems to be as commonplace as the complaint that this approach produces poor efficacy detection.  The link is that fast, competitive enrollment may occur at the expense of quality enrollment.

The cliché “haste makes waste” comes to mind. Unfortunately, a fast and poor quality study can significantly delay or even “kill” what otherwise would be an effective treatment.  The compressed and competitive approach all too often yields a result which in the end is not truly fast, cheap, or good.

If you have a novel mechanism of action study and want to avoid the pitfalls that I have just discussed, please feel free to contact me at (316) 293-1833. I’d be happy to visit with you.