On June 5, 2012, the Department of Health and Human Services Office of Inspector General (“OIG”) released a report titled “Scientific Disagreements Regarding Medical Device Regulatory Decisions.” A number of scientific disputes at the Center for Devices and Radiological Health (“CDRH”) received media attention between 2008-2010. Perhaps in an effort to address the management of scientific disputes, in October 2009, CDRH issued new policies and procedures addressing their resolution. The OIG report was intended to: 1) describe the types of disputes that arose between 2008-2010; 2) determine whether CDRH followed the requisite procedures and regulations when addressing such disputes; 3) assess the implementation of the new policies and procedures; and 4) identify challenges in addressing scientific disputes.
The October 2009 guidance formalized the process to resolve internal scientific disagreements. The first step in the process is an informal discussion between the reviewer and the manager. If that discussion is unsuccessful, the manager may submit an “initiation memorandum” to the Ombudsman, who reviews the memorandum to determine “whether it is complete and eligible for the new process.” To be eligible, “the disagreement must be scientific and related to a regulatory decision.” The Ombudsman then assigns a manager not involved in the initial disagreement to review the memorandum, discuss the disagreement with involved parties, and attempt to resolve the issue. If resolved, the reviewer and manager submit a “joint memorandum” to the administrative file documenting the resolution and its basis.
If the dispute is not resolved, the manager “must make a decision on each disputed issue on the basis of a review of evidence in the administrative file and any other relevant resources” and must document that decision in a decision memorandum that will be included in the administrative file. The manager must then send the memorandum to the Ombudsman and all involved parties. If any party is not satisfied, he or she may appeal for review by a higher supervisory level, up to and including the Center Director, after which the appeal may be taken to the FDA Commissioner.
In reviewing use of the scientific resolution procedures and applicable regulations, OIG used the following sources: “CDRH administrative files; an online survey of CDRH reviewers and managers; interviews with CDRH officials and other stakeholders; and CDRH's current and former policies, procedures, and guidance documents.” OIG ultimately identified 36 administrative files to review, 33 of which used the pre-October 2009 procedures, and three of which used the new, more formal procedures. OIG acknowledges that the actual numbers of agreements could have been much higher, since CDRH did not begin tracking scientific agreements until 2010.
The scientific disagreements reviewed by OIG involved a variety of issues, and were not often directly related to clearance or approval of a medical device. Rather, only 1/3 of the resolutions led to the clearance or approval of a device. The other 2/3 dealt with processes prior to clearance or approval. This may serve as some comfort to individuals who believed, based on publicly available information, that many of the disagreements between reviewers and managers led to managers making decisions to clear or approve devices when the reviewers expressed concern about the safety or effectiveness of the device. The OIG report indicates that many of the issues for 510(k) devices were related to whether a device was eligible for review through the 510(k) process, appropriate device labeling, and identification of an appropriate predicate device. For PMAs, disagreements related to clinical trial design, the need for additional data, and appropriateness of labeling.
OIG also looked at the type of documentation included in the administrative files, and found that five of the 36 lacked any documentation related to the disagreement, and 22 contained formal memoranda. Nine files contained emails or other documentation referencing the scientific disagreements, rather than formal memoranda. OIG found that CDRH has not specified who is responsible for upkeep of the administrative file and documenting decisions related to the disagreement. Additionally, OIG found that not all CDRH managers and reviewers were trained on the new scientific disagreement procedures released in October 2009, and CDRH did not track who received the training. Many reviewers stated that they do not even know how to initiate the new procedures.
Perhaps one of the most interesting findings is that approximately 20% of survey respondents indicated they were concerned that expressing a scientific disagreement to management could adversely affect their careers. OIG also found a small numbers of reviewers who “reported incidents in which they felt some pressure to change elements of their written reviews or to not document a scientific disagreement.” The majority of respondents, however, indicated they felt comfortable discussing scientific disagreements with their peers and managers.
Based on its findings, OIG recommended FDA do the following: 1) define more clearly its requirements for documenting and resolving scientific disagreements; 2) train all reviewers and managers on the new policies and procedures for resolving scientific disagreements; and 3) more clearly assign accountability for the contents of the administrative files of all submissions. The OIG report states that FDA concurs with the recommendations and has outlined plans to implement them. Hopefully, reviewers will feel comfortable taking advantage of the procedures available to them to express disagreements without fearing an adverse impact on their careers. Because this report included a review of only three disagreements undertaken in accordance with the new procedures, it will be interesting to see, in a few years, what impact the new procedures have on the resolution of scientific disagreements.