Investigational plans, or protocols, are developed with what authors believe are clear inclusion and exclusion criteria that must be confirmed prior to the initiation of any investigational treatment or test. There are certain inclusion criteria that are common including an age range, willingness to provide consent and adhere to the study schedule, and particular condition or diagnosis. Common exclusion criteria include a past medical diagnosis, excluded treatments or medications, or family history of a certain disease. According to 21 CRF 812.110 (b), it is the investigator’s responsibility to conduct the trial according to the investigational plan and therefore, adequately review medical history, interview the subject, and obtain labs or imaging to confirm that all inclusion and no exclusion criteria are met.
Seems pretty clear, right? Not always!
Take this example- for a particular study; there is no specific exclusion for weight or BMI. However, the protocol states that subjects who exceed a certain BMI, calculated by the EDC post enrollment, will not be included in the statistical analysis. A sharp research coordinator asks the question - “If it is obvious that a subject is obese, should I even consent them for participation?”
The investigator directed the coordinator to screen everyone regardless of the appearance of the subject, as the exclusion criteria does not clearly state that a certain weight or BMI is prohibited.
How about this example - a protocol states that a subject may not have any condition that will limit life expectancy less than 2 years. Should a subject be enrolled with a history of prostate cancer that is in remission? As a physician, what information would you need to know to ensure that a subject does not meet these exclusion criteria? How about if you are a monitor-what documentation would be acceptable in the subject’s medical record for you to source data verify this item?
It is common that a protocol is amended shortly into the life of a study due to changes or clarifications of inclusion and exclusion criteria. In addition, monitors often find documentation in the medical record not previously noted by the study staff that excludes a subject.
Do you have any tips for protocol developers to ensure clear inclusion/exclusion criteria?
Do you have any tips for study sites to ensure that all inclusion/exclusion criteria are met?
Do you have any tips for monitors verifying inclusion/exclusion criteria? Please share below.