Updated on 5 September 2013
Whether investigator site staff complies closely with a protocol may, in extreme cases, determine the success or failure of an Investigational Medicinal Products on trial.
When drugs are trialed in patients, they move into a clinical setting in which the busy routine care of patients, rather than the conduct of drug trials, is usually the main preoccupation of investigators. The
extent to which a sponsor can control this process is much less than in earlier phases of drug development.
Investigator sites participate in trials by choice and sponsors often compete for their collaboration. It is perceived by many sponsors that a light touch has to be employed in correcting problems in order to prevent alienation of sites for future trials and in some instances to maintain relationships with key opinion leaders.
Whether investigator site staff complies closely with a protocol may, in extreme cases, determine the success or failure of an Investigational Medicinal Products (IMP) on trial. Noncompliances and protocol violations may overwhelm the power calculations with which a trial is designed.
A typical example is the phenomenon of ‘compassionate elasticity', whereby investigators may stretch inclusion or exclusion criteria to enroll some unsuitable patients with serious unmet needs to a trial. Further examples relate to a failure to recognize and/or manage toxicity appropriately, an effect that may particularly be evident in trials of drugs with narrow therapeutic indices. Such failures at site
level may be the death-knell for a new drug that might have otherwise succeeded. They probably represent the greatest vulnerability to success in later phases of a drug's development, beyond any intrinsic failings of the product itself. The frequency and cost of such failures is likely to be very high, not least for patients, who might have benefited from the drug getting on the market.