Talk to FDA Early About Foreign Clinical Data: Analysis
While FDA is stepping up scrutiny of foreign clinical trials, particularly studies conducted outside an IND (see earlier story), drug sponsors should discuss their plans to rely on foreign data with FDA early in development, including at pre-IND meetings, and put greater emphasis on site selection, monitoring, investigator training and FDA access to underlying records. That are some of the recommendations in a new legal analysis by attorneys at Foley Hoag. The agency’s actions are focused on ensuring that overseas data used to support U.S. drug applications meet good clinical practice, data integrity and patient-population requirements.
FDA has indicated it will pay particular attention to foreign studies not conducted under an IND and ensure application reviewers rely only on studies that meet applicable regulatory requirements. It has stressed that the increased scrutiny is not intended to discourage overseas trials. Rather, the agency’s position is that studies must meet U.S. evidentiary, inspection and human-subject protection requirements regardless of where they are conducted.
The analysis notes that under 21 C.F.R. § 312.120, FDA may accept data from a foreign study not conducted under an IND if the trial was conducted in accordance with GCP, received independent ethics committee review, obtained and documented informed consent, and is available for FDA inspection. Sponsors must also provide information on investigator qualifications, research facilities, study monitoring and measures used to ensure GCP compliance. Failure to satisfy the requirements can result in FDA declining to rely on the data for an IND or marketing application, it says.
Population representativeness is becoming another significant issue, according to the attorneys. For approvals based solely on foreign clinical data, FDA regulations require the results to be applicable to the U.S. population and U.S. medical practice. Differences in genetics, demographics, disease prevalence, standards of care and healthcare systems can complicate that determination.
FDA has encouraged sponsors to include sufficient U.S. participants and develop trial populations reflecting the diversity of regions where a product would be used. Inadequate representation could result in requests for additional U.S. studies or supplemental enrollment, potentially increasing development costs and delaying applications.
The analysis also points to FDA's limited capacity to inspect foreign clinical sites as a continuing data-integrity concern. Potential problems include inadequate source-document verification, deficient monitoring, unreliable electronic data systems and, in more serious cases, fabricated or falsified data.
FDA officials recently said the agency is increasing resources for bioresearch monitoring inspections, expanding communications with sponsors and providing additional training to reviewers evaluating studies from sites considered at greater risk for data-integrity problems.