FDA's Center for Drug Evaluation & Research will run a one-year test of a formal dispute resolution process to resolve differences of opinion among reviewers.

CDER implemented a Manual of Policies & Procedures entitled "Documenting Differing Professional Opinions and Dispute Resolution" Nov. 4. The ¹ MaPP outlines a process for using ad hoc panels to arbitrate internal disputes, with a plan to evaluate "the pilot after one year to determine whether it adds value to the regulatory decision making process."

FDA announced the new process Nov. 5 as part of a package of drug safety initiatives (see ² Also see "IoM Drug Safety Study May Buy Time For FDA; Report Will Play In PDUFA IV" - Pink Sheet, 15 November, 2004.).

One theme of the publicity surrounding both the Vioxx withdrawal and the safety of antidepressants in children is the claim by safety reviewers that analyses of risk information have not been given enough weight by FDA decision makers.

The development of the internal dispute resolution policy began more than a year ago, before the antidepressant and Vioxx issues emerged.

Acting CDER Director Steven Galson talked about the effort during an interview with "The Pink Sheet" in November 2003. The policy was intended to "formalize" standard agency practices for resolving scientific disagreements, Galson said (³ [A#00650470015], p. 19).

At that time, the highest profile issue about internal disputes involved allegations by Office of Drug Safety epidemiologist David Graham that the agency presented a distorted picture of the risk-benefit profile of the arthritis drug Arava during an advisory committee review of adverse events seen with the product (⁴ Also see "Aventis Arava Liver Toxicity Warning Is Satisfactory, FDA Arthritis Cmte. Says" - Pink Sheet, 10 March, 2003., p. 6). Graham is now at the center of questions about Vioxx (⁵ Also see "Celebrex Long-Term Safety Monitoring Results Reassure FDA" - Pink Sheet, 8 November, 2004., p. 14).

During a Nov. 5 media teleconference, Galson observed that "many of these high profile cases are all being reported by the same individual."

He emphasized his belief that concerns about the handling of dissent are "very unusual." When "they do occur, they get a lot of publicity," Galson acknowldged. However, "that shouldn't be confused with diagnosing a systemic problem, because we don't think there is one."

The dispute resolution policy does appear to have evolved in the drafting process to build in an extra layer of review in the form of ad hoc panels to adjudicate disagreements.

The MaPP lays out a process by which individuals within the center can declare a "Differing Professional Opinion."

A reviewer can submit a request for a review to the CDER ombudsman. The ombudsman, in consultation with the CDER director, will determine whether the issue merits convening a panel. The ad hoc panel will "usually" be chaired by an office director, appointed by the CDER director, who will then choose two or three additional members.

"To the extent possible, DPO panels should not include individuals who have directly participated in the decision-making process up to the time of the DPO," the MaPP states. "However, they should include individuals with the relevant technical expertise and experience to understand the complex issues at hand."

FDA intends to use outside consultants in the process "when appropriate and feasible," the MaPP states.

The panel will make a written recommendation to the center director within 30 days of beginning its review; the center director will then issue a decision on the dispute within five days, the MaPP states.

Galson emphasized that FDA does not want the DPO process to become an obstacle to timely decision-making by FDA. However, "where there are important safety concerns, it is important that we consider them."

"These DPO procedures are not intended for the resolution of routine disputes that can be addressed through the normal procedures for documenting and responding to different scientific and regulatory viewpoints," the MaPP states.

"Rather, the DPO procedures should be reserved for the most serious differences of opinion when an action or inaction by CDER could have a significant negative impact on public health."

CDER Dispute Resolution Policy Will Test “Ad Hoc” Arbitration

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