Concept



Attempts to solve the growing problems of high placebo response and failed CNS studies have not resulted in more CNS therapies available for patients. Current protocols have become increasingly more difficult and expensive to implement due to intensive rater training, additional subject ratings, centralized diagnosticians and raters and more exclusive I/E criteria. As a result, major Pharma is now less willing to invest in CNS drug development and some have pulled out of CNS drug development altogether.

Of greatest concern to many investigators and sponsors is the rising prevalence of duplicate or dishonest subjects. While most subjects enter clinical trials for all the right reasons, a statistically powerful number of subjects have found that they can participate in several studies at once. They tell investigators what they need to hear in order to be enrolled and then may not take study medication. Websites designed to assist professional subjects are easy to find: GPGP (guinea pig guinea pig).net, JALR (Just Another Lab Rat).org, for example.

To date duplicate subjects have only been tracked within some pharmaceutical companies. While such internal data is not shared, best estimates are that at least 5% of subjects are duplicates within the same protocol or program. This is only the tip of the iceberg, as nothing tracks participation across sponsors or indications.

Of concern is that proposed solutions to the placebo-response problem may serve to magnify the effects of professional subjects. Raising the entry criteria (increasing the inclusion MADRS from 22 to 26 in a depression study, for example) to enroll an enriched sample is a clear benefit to clinical trial design. Professional subjects, however, may report severe symptoms to exceed ratings criteria, only to improve dramatically and skew study results. Truly depressed (and often more stoic) subjects will be excluded when they fall just short of entry criteria. Even a small number of professional subjects who do not take study medication or placebo respond can influence study results.

Additionally, financial incentives for subjects, sponsors and investigators almost certainly contribute to the problem.

Central recruiters are paid for the number of subjects they deliver to sites.

A subject will be "reimbursed" more if he or she participates in several studies at once. A professional subject may be rejected at some sites, only gaining acceptance when the proper history and severity are learned.

Pharmaceutical or CRO staff may not focus on professional subjects when the pressure is on to meet enrollment timelines. Much is spent on recruitment and retention, without little attention to who is being recruited and retained.

Investigator incentives can also be perverse. Site time spent recruiting and thoroughly pre-screening will not be recovered unless the subject signs consent. Once screened, both investigator and subject will continue to be compensated only as long as the subject remains in the study.

These incentives, coupled with higher unemployment, the rise of the internet and a culture that has come to accept cheating may be responsible for the growing number of professional subjects.

We need a basic understanding of who our subjects are: Are they currently participating in other studies? Have they participated in other studies within the timeframe excluded by the protocol? Have they been in a study for an excluded indication?

A trial subject database should be simple to use and not add to study complexity. It must be acceptable to subjects, HIPAA compliant and secure. It should give investigators and pharmaceutical companies a basic mechanism to weed out professional subjects who can disproportionately affect a clinical trial.

It is time for CTSdatabase!