Another viewpoint on the post: A Question of Significance

I received this comment on my post A Question of Significance (scroll down) from another clinical trials consultant. Since comments on posts are pretty well hidden, I thought I would post this response. It is regarding the need for a well-trained and supervised FDA inspectional workforce. There is also a thoughtful question/comment on the post regarding Dr. Schultz along with my reply. Here are the comments of Tania Issa who has years of experience as a clinical trial monitor:
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Tania Johnstone Issa
August 10, 2009 at 5:47 pm
Carl,

I fully agree with your position. Over the years I have worked closely with sites as a CRA/monitor, project manager, program manager, and QA auditor. I have seen investigators who have been terribly negligent in regards to patient safety. Just as bad, I have seen investigators who enroll marginally eligible or ineligible subjects or keep subjects on drug/device beyond the safety parameters in the protocol, enticed by enrollment incentives and other site payments. Yet when these same sites were inspected by FDA, many of the obvious and dangerous deficiencies went unnoticed, allowing the drug to be approved and the investigator to continue managing patients in other clinical trials. I have also seen excellent investigators receive 483s for minor deficiencies which had no impact on patient safety or data integrity. Enforcement is terribly absent and, at the same time terribly misplaced.

Carl has correctly emphasized that the FDA workforce inspecting sites and sponsors needs a thorough overhaul. Many of the basic principles of site monitoring, which are focused on (and quite adept at)ensuring patient safety and data accuracy, should be incorporated into FDAs inspection program. Well-trained monitors/CRA regularly identify lack of protocol adherence and patient safety issues, documenting these in reports. Because these reports are ultimately buried in paperfiles into perpetuity, rarely requested by the FDA, the agency charged with ensuring we have a safe drug supply, inspects sites but does not bother to read the eye-account written story of the site’s participation and the experience of their patients. Absurd, considering the FDA requires biopharmaceutical companies to perform this monitoring.

Many FDA inspectors lack any clinical experience and cannot comprehend what is written in study protocols, case report forms, medical charts, and monitoring reports. If biopharmaceutical companies are bound by FDA to select monitors “qualified by training and experience”, the FDA should do even better with the FDA staff responsible for Site/Sponsor inspections.

Because the clinical trials industry continues to express sincere concerns about the safety of investigational products, and bemoans lack of meaningful regulation from FDA, the industry has been self-disciplined enough to collaboratively identify and incorporate best practices (beyond regulations) truly designed to protect patient safety. Now it is time (pastdue) for REAL REFORM which should include a serious review of existing regulations against industry best practices.

Luckily, the ICH has by and large, has avoided the many constaints of political party affiliations, changing administrations, and lobbyists, using their efforts along with public input to provide meaningful guidance/regulation. Since the FDA references ICH as guidance instead of adpoting ICH as regulation, drugs and other investigational products approved for commercialization in the US are not approved against the highest standards already in use by many countries around the world. Luckily, however, many US companies have adopted the higher standards of ICH while they wait and wait for FDA to……..

Dr. Schultz resigns as head of FDA’s medical device center

The industry newsletter, The Gray Sheet and the Wall Street Journal both reported that Daniel Schultz, MD, Director of the Center for Medical Devices and Radiological Health (CDRH) offered his resignation to Dr. Margaret Hamburg, the new FDA Commissioner. Schultz said that the resignation was an agreement between him and Hamburg stating that Dr. Hamburg agreed his resignation “would be in the best interest of the center and the agency.” That doesn’t look good on your CV.

Dr. Schultz was under many clouds of suspicion. There have been serious charges leveled at the management of CDRH by employees conducting scientific review of new medical devices submitted to FDA. This is actually a very big deal. The Gray Sheet article is attached on the Blogroll as, “2: Schultz resigns.” I am very curious who else will be resigning in the Hamburg Era.

UPDATE: The Wall Street Journal reports on Dr. Janet Woodcock, Dr. Schultz’ counterpart at the Center for Drug Evaluation and Research, having conflict of interest problems. Read their coverage on the Blogroll: “11WSJ: Drug chief accused of conflict.”