In response to the controversy created by diabetes drug Avandia (GlaxoSmithKline), the House Appropriations Subcommittee on Agriculture, Rural Development, Food and Drug Administration, and Related Agencies held a hearing on drug safety.
Chairwoman Rosa DeLauro (D-CT) noted in her opening statement that “pharmaceutical companies are applying our country’s greatest resource – its innovative spirit – to help more people live longer, healthier, more productive lives by bringing life-saving drugs to the marketplace.” She added further that “most people at some point experience the direct reach and power of these drugs to cure illness, heal wounds, or halt disease.” Ms. DeLauro herself acknowledged her own experience with life-saving drugs “when more than 20 years ago, she was diagnosed with and survived ovarian cancer.”
The Chair also recognized how there are “many competing issues in play when the FDA is weighing whether a particular drug is safe enough to be on the market.” One of the important issues Ms. DeLauro pointed out was that “sometimes, people suffering from a given illness, after consultation with their doctors, will willingly accept some extremely severe side effects for a chance at relief or recovery.” The ability of FDA to make such drugs available to patients in a timely matter so they can have such choices is crucial.
For the agency to give patients the options of safe and effective drugs, FDA’s scientists and regulators need to have all the pertinent information about a given drug at their disposal to bring such treatments to patients. They also need the regulatory tools and the regulatory science capacity to draw their own independent and unbiased assessments of a drug’s safety. Ms. DeLauro noted that the agency needs the structural and the political capacity to ensure its recommendations are put into action, followed, and enforced if a drug is deemed unsafe by the agency.
She believed the latter capacity was essential considering two scientists at the FDA’s drug safety office in June of 2007 recommended that Avandia be removed from the market, but nothing came of the decision.
She discarded the fact that the FDA held a panel of 23 advisory committee members to discuss Avandia and they voted 22-1 in favor of keeping Avandia on the market.
The Chair was even more alarmed by the fact that Avandia is still on the market now, pending the findings of the TIDE study, which is expected to be published in 2015. In her opinion, FDA should not be taking so long “to study a drug about which such serious safety issues have been raised.”
The fact that over 200 advisory committee positions at the FDA remain unfilled for advisory committees that conduct such research and trials to test the safety and effectiveness of drugs, is one reason why there are such delays.
Another reason for the delay is that FDA summoned an advisory committee on Avandia, and that advisory committee voted 22-1 in favor of keeping Avandia on the market.
According to the chairman, these apparent weaknesses in FDA show a “dangerous and systemic failure in regulatory apparatus.” As a result, Congresswoman DeLauro called for the need to establish a more independent regulatory science capability, so that the agency can make evaluations about drug safety free of industry pressure. She also called for more disclosure and transparency from the pharmaceutical companies themselves. Accordingly, the Committee heard testimony from:
– Senator Chuck Grassley, Ranking Member, Senate Finance Committee (Testimony)
– Harlan M. Krumholz, MD, MSc, Professor of Medicine(Cardiology), Yale School of Medicine (Testimony)
– Sidney M. Wolfe, MD, Director, Health Research Group of Public Citizen (Testimony)
Senator Grassley
Mr. Grassley’s testimony highlighted his experience with the Senate Finance Committee investigating Avandia back in May of 2007, when the New England Journal of Medicine published a study which found that Avandia may cause heart attacks. While the majority of his testimony talked about the findings from this investigation, which were published in a February report, he used the example of Avandia to discuss his “legislation to establish an independent office of drug safety at the FDA.”
As proposed, the “Center for Postmarket Drug Evaluation and Research“ would tackle the lack of equality between the Office of New Drugs (OND), which decides whether to approve a drug, and the Office of Surveillance and Epidemiology (OSE), which monitors a drug’s safety once it’s on the market and being sold to patients.”
Senator Grassley emphasized the need for individuals in the office responsible for post-market surveillance to be allowed to provide an “independent opinion” based on the best available evidence. He also called for giving FDA employees who conduct post-market surveillance the ability to express their opinions in writing and independently without fear of retaliation, reprimand, or reprisal.
He also noted that FDA needs a complete and accurate list of all of the products sold on the US market, including unapproved drugs, so the agency is able to take appropriate enforcement actions.
Harlan M. Krumholz, MD
Using his experience as a researcher and plaintiff’s expert in the Vioxx case (Merck), Dr. Krumholz used his testimony to draw parallels between Avandia and Vioxx. In looking at both cases, he noted the need “to ensure that information from clinical trial research is available to make sound, reasonable decisions about the drugs and devices being evaluated and to improve communication of trial results among patients, clinicians, policymakers, and drug manufacturers.”
Dr. Krumholz also recognized “the challenges facing regulators as they evaluate drugs for approval or for new indications, and the challenge of making use of all available clinical trial data to better understand drug efficacy and safety.” He noted that one reason all available clinical trial research is not available, and researchers make inferences about drug safety is because researchers “lack the appropriate studies.” This happens, in part, “because not all clinical trial research is published, and not all data collected within a clinical trial is published, even when the main findings are.” As a result, he made 3 recommendations:
– Increasing transparency in the clinical trial research process by making “raw data files available” and posted within 12 months of a study’s completion. Dr. Krumholz wants this data published because it allows for the “most accurate and rigorous evaluation, allowing an assessment of quality and validity and enabling standardization of the analyses across studies and direct calculation of pertinent outcomes;”
– Convening at least two groups of expert, non-industry–affiliated investigators to conduct an independent evaluation of the data and report to verify findings if concerns are raised about a drug by the manufacturer, or the FDA, or by outside investigators; and
– Have the FDA commission an independent and impartial panel of experts to review the analyses and provide a report to Congress, made available to the public, comprehensively detailing what is known about the drug’s efficacy and safety, if concerns about drug safety are verified
Dr. Krumholz also discussed the need to improve communication of trial results among patients, clinicians, policy–makers, and drug manufacturers, particularly what is known about the expected benefits and risks of drugs. He also mentioned Section 3507 of the recently enacted Patient Protection and Affordable Care Act of 2009, which requires the addition of quantitative summaries of the benefits and risks of prescription drugs in a standardized format (such as a table or drug facts box) to the promotional labeling or print advertising of such drugs.
Following these recommendations, Dr. Krumholz believes that sharing data will improve drug safety the way it has already improved the area of quality of care. He asked that physicians and researchers avoid drugs without proven clinical benefits and with proven risks, and recommended that they clearly disclose to patients when they do not know if drugs have a beneficial effect.
Sidney M. Wolfe, M.D.
As the Director of the Health Research Group at Public Citizen (one of Ralph Nader’s groups), Dr. Wolfe’s testimony called for the TIDE study, requested by the FDA, to be stopped immediately, and to remove rosiglitazone from the market. In his comments, he cited various studies that showed the harmful side effects of rosiglitazone, and he explained various reasons why he believed the TIDE study is unethical.
Discussion
It is disconcerting that the witnesses at this hearing all came from the same point of view. There was no endocrinologist specializing in diabetes and no witnesses from the FDA to describe how much work goes into surveillance and the need for unified agency communication. I am sure the congressman would not want members of their staffs publically speaking out issues without a vetting practice, yet there was much discussion that this should be the practice at the FDA.
The hearing which was held in the House Appropriations subcommittee on Agriculture highlights one serious disadvantage that the FDA faces in increasing their funding.
Funding appropriations to expand operations such as monitoring drugs coming from China and India and other surveillance is initiated in an Agriculture Subcommittee (that is right agriculture)
The FDA was started with the goal of monitoring food safety and since its start the agency has greatly expanded in the area of drugs and devices. This explains why the FDA is always under resourced, medical products and agriculture products come from very different areas of the country. Members of congress generally don’t join the agriculture subcommittee to work on drug related issues.
In the wake of all these recent drug scares, American’s have begun to realize that drugs and medicine have risks. But everything in life has risks. While it is certainly unethical and illegal to hide those risks or portray them in a different light, FDA’s approval and testing process rests on two words: “safe” and “effective,” words that have extremely different meanings for different people. For example, a young father may think a new cancer drug is safe and effective, whereas an elderly grandmother may think a hip replacement is not safe or effective.
Accordingly, whether FDA can remain the protector of drug safety in the future is in question now, as hundreds of positions remain empty, and it is becoming more apparent that the agency lacks the funding, staff and resources to accomplish many of its goals. These problems only become worse as millions of people will be added into the health care system, which will inevitably demand more treatments, drugs, and devices to be approved for their health and safety.
Patients need to be in a position to make a fully informed decision about taking a drug. Likewise, physicians must be given all information and clinical data about the research of such drugs, and advise their patients accordingly because most people at some point will need drugs to cure illness, heal wounds, or halt disease. While some patients may not be willing to take the risk, some people suffering from a given illness, after consultation with their doctors, will willingly accept some extremely severe side effects for a chance at relief or recovery. Finding ways for physicians to share clinical data about risks and benefits of drugs with their patients will help make these decisions easier for patients.