Friday, June 03, 2011

Restructure FDA's Drug Review Process?

Last week, I had a chance to listen to a speech by Dr Scott Gottlieb. While he touched several topics in related to the health care reforms, I was specifically interested in his discussion on restructuring FDA’s drug approval process.

Dr Gottlieb gave a lot of insights within FDA and analyzed the root cause of the very long and inefficient FDA drug review process.

Following his speech, I located his paper “SHOULD FDA RESTRUCTURE ITS DRUG REVIEW PROCESS?” from FDLI’s website. A lot of his analyses are so true and to the point.

For example, he elaborated why FDA adopt a matrix management structure for its review program.

“Prior to FDA’s adoption of a matrix management structure for its drug review program, agency scientists were organized largely around the clinical areas in which they worked (oncology, cardio-renal, antiviral, etc). This therapeutically focused structure had some advantages, but also led to some of its own challenges. FDA’s adoption of a matrix structure was aimed at solving some of these problems.

For one thing, sponsors complained that the advice they received about disciplines like biostatistics or clinical pharmacology varied (sometimes significantly) across different therapeutic divisions. Statisticians in one clinical division would be interpreting certain principles of statistics or evaluating a particular protocol design in a manner different than statisticians inside another therapeutic division.

These discrepancies still occur. But it is believed that the matrix organizational structure cuts down on this sort of conflict.

Grouping all of the statisticians or pharmacologists inside the same office increases opportunities for comparable training and cross-calibration on key principles. CDER management pulled the first group of the review divisions—the chemists—in 1995. The impetus was differences in pharmaceutical quality requirements being maintained among the different clinical divisions. Ultimately, having the chemists organized as a single group fostered the development of consistent standards. It also enabled FDA to negotiate the standards established by the International Conference on Harmonization (ICH).

Another reason for establishing the matrix was to improve morale. FDA remains a very “physician centered” culture, but was much more so prior to adoption of the matrix. Staff who lacked medical degrees or who weren’t the clinical reviewers on an application sometimes complained that they felt marginalized in the review process. As one statistician told me, “we were treated like second-class citizens.” Specialists from non-clinical disciplines like statistics also complained that remaining immersed in a single therapeutic area didn’t give them the breadth of experience that they needed for their own professional development.

Similarly, the organization of scientific personnel by therapeutic area was also seen as an impediment to their continued training in their chosen disciplines. For example, statisticians came together for the equivalent of grand rounds or other kinds of shared learning experiences. But these kinds of cross-training opportunities were challenging because staff were ultimately accountable to their divisions. The shared training opportunities weren’t prioritized. Efforts were also made to rotate non-clinical experts across different therapeutic areas. But the challenges endured.”

He then went on discussing the issues with FDA’s weak matrix management structure.

“But in practical terms, the weak matrix means that FDA project managers have limited dominion over key aspects of the review. Key disciplines involved in the review aren’t accountable to the project manager, or the division director. It is a system where there are few management carrots and no sticks. This weak structure also makes it harder to organize collaborative projects or even team meetings. The project manager doesn’t have strong authority when it comes to managing the collaboration between the different scientists involved in a drug’s review.”

He also mentioned the quality of the FDA review scientist and issues with FDA’s policy to allow very flexible working hours and work-from-home schedule. The current FDA drug review team is loosely organized and inefficient in many aspects. However, it is not easy to make big changes to the current process.

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