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Budget decisions that impact patient safety
Medelis: The FDA requires that clinical studies are reviewed and approved by an Institutional Review Board. How effective is the IRB in enforcing safety?
Dr. Gourzis: The IRB is involved before the study is initiated and then during the study at intervals appropriate to the degree of risk for patients. In addition, the IRB must be notified of unanticipated problems and changes in research activity.
In the years since the FDA regulations were issued, there have been a lot of changes in clinical trial reporting due to, for example, multi-center studies and international trials. These changes have exponentially increased the volume of data generated by clinical trials.
Today, IRBs are also receiving increasingly large volumes of individual adverse event reports. These reports often lack the context and detail that the IRB would need to fully analyze the data. Thus, the IRB’s ability to assure the protection of human subjects is limited.
Medelis: How can a Data Monitoring Committee / clinical safety committee improve the safety of a trial?
Dr. Gourzis: DMCs are objective, arm’s length arbitrators and represent an important safety measure.
A DMC typically consists of three to four members who are identified up front to the IRB and FDA. They meet at specified intervals to review data from one or more ongoing clinical trials according to a pre-determined protocol.
DMC members are familiar with the disease state under study but they do not participate in the study. Instead, they advise the sponsor on two major issues: one, the continuing safety of trial subjects and two, the continuing validity and scientific merit of the trial itself.
As long as the DMC determines that there are no safety issues, the study proceeds. However, if they see something that requires additional scrutiny, they may request further review of the data. In some cases they may even stop a study pending that further review of data.
For the DMC to be effective, however, it’s up to the CRO and the sponsor to ensure that the DMC gets the information they need in a timely fashion.
Medelis: Is a DMC mandatory?
Dr. Gourzis: In big studies, particularly if there is either an important efficacy end point, or safety end point, or a safety monitoring issue, the FDA will insist on it. For example, DMCs have generally been established for large, randomized multisite studies that evaluate treatments intended to prolong life or reduce risk of a major adverse health outcome, such as a cardiovascular event or recurrence of cancer.
In addition, DMCs are generally recommended for any controlled trial of any size that will compare rates of mortality or major morbidity.
Working closely with the sponsor and the CRO, the DMC adds another set of eyes focused on safety and trial validity and helps prevent the nightmare scenario we discussed earlier.
Medelis: What’s the single most important recommendation for medical officers concerned about improving patient safety?
Dr. Gourzis: A DMC should be considered in every study, both for safety and an objective voice to the sponsor. For example, if interim data suggest a negative efficacy or side effect profile, the DMC may recommend the study be terminated to avoid needless patient exposure and potential costs to the sponsor.
I would also recommend bringing the DMC into the loop quickly – ideally in the planning stage of the study.
Medelis: How about recommendations regarding trial budget and operations to optimize patient safety?
Dr. Gourzis: While a medical officer may be tempted to shave time off site monitoring to control costs, I’d highly recommend against it. If it’s a rare disease where patient enrollment is monthly, the standard monitoring interval is typically once every four to five weeks. But if it’s a condition where enrollment is fast and furious, it may be prudent to increase that monitoring frequency in order to keep on top of the data.
More frequent monitoring can get very time intensive in oncology studies since these patients typically have voluminous medical records. Effective monitoring may require up to 16 hours per patient. A pushback on time to reduce costs may be false economy.
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