The effects of early stopping because of efficacy go far beyond the trial itself, with implications for ongoing and future studies of the same disease. “If you stop early and declare that you have a [new] standard of care, does that impact other ongoing studies that are not using that [new standard] of care arm, or does that impact the planning for the next generation of studies?” Dr. Schilsky asked. “You may find that the accrual to other ongoing trials screeches to a halt because everyone says 'this trial design is no longer relevant in light of this new information.'”
Making the Decision
Ultimately, the decision to stop a trial early is in the hands of the safety data–monitoring committee (DMC). “This sort of data release is almost always undertaken only after a very thorough review by an independent data-monitoring committee,” Dr. Schilsky said. “DMCs are in the best position to make these decisions and they do it only after lots of careful deliberation.”
Ideally, the DMC should weigh in and make a recommendation on what should be done for the patients who are in the control arm of the study, at the very least, he said.
In the case of lenalidomide for multiple myeloma, “the study was markedly positive in favor of the Revlimid maintenance, and led our data- and safety-monitoring board to recommend early release of the results,” Dr. Schilsky noted. Accrual had been completed and all patients were in follow-up, but “the study crossed a statistical boundary for early release of the data before the protocol-specified number of events for the final analysis was available.”
This process involved notifying the Food and Drug Administration, the National Cancer Institute, and the drug manufacturer, as well as developing letters for physicians and patients involved in the study, and sending out a press release. In this case, because lenalidomide is already available, oncologists could start prescribing the drug for this patient group immediately.
Advancing technology and the development of more personalized medicine may help resolve some of the issues concerning the early stopping of trials, Dr. Crawford suggested.
“What will solve this will be biomarker-directed treatment subgroups. … We can look at a much smaller sample of patients because we're looking at a much bigger effect,” he said. “In the long run, that's going to be a much better approach to oncology than continuing to treat thousands of patients with treatment A vs. B.”
Disclosures: Both Dr. Schilsky and Dr. Obel said that they have no significant financial relationships. Dr. Crawford has received research support from and been an adviser, speaker, or consultant for several pharmaceutical companies.
'There's this risk that you put the data out there early, and it doesn't hold up over time.'
Source Dr. Schilsky