The case involves a woman, Diana Levine, a musician who suffered from migraines and who lost an arm as a result of a devastating side effect from an apparently bungled IV injection of phenergan. In an editorial entitled "The Court Confronts a Grievous Injury", New York Times, Nov. 7, 2008, the case is summarized:
Ms. Levine went to a clinic seeking relief for a migraine headache. She received Demerol for her headache and Wyeth’s Phenergan to combat nausea, both administered by injections into the muscle, which is the preferred route of administration. When the headaches persisted, she returned for more treatment.
This time, the same medicines were administered by an intravenous “push” technique that is known to be risky — using a needle inserted into a vein. A physician’s assistant mistakenly hit an artery, with catastrophic results. Ms. Levine quickly developed gangrene; her hand and lower arm had to be amputated.
She sued the physician’s assistant, the supervising physician and the clinic for malpractice and won an out-of-court settlement ... Then she sued Wyeth for failing to warn the clinicians to use the much safer “IV drip” technique, in which the drug is injected into a stream of liquid flowing from a hanging bag that already has been safely connected to a vein, making it highly unlikely that the drug will reach an artery.
A trial court awarded $6.7 million, and the Vermont Supreme Court upheld the verdict. Now Wyeth has asked the U.S. Supreme Court to reverse the verdict on the grounds that Wyeth complied with federal regulatory requirements [e.g., the product labeling that was approved by FDA]. The federal government at high levels apparently supports this position.
In other words, Wyeth and its governmental and other supporters are arguing that the FDA is the "gold standard", the emperor of drug adverse events warnings and labeling, and that the decisions made by the emperor override state laws and pharmaceutical industry's own judgment and warning efforts (or lack thereof).
If the FDA approved it, then the matter is settled. The emperor has spoken. The gold standard pre-empts lowly silver and copper wannabees.
In an ideal world, this might be a reasonable position.
In this real world, however, I find this position risible, objectively unsupportable, and dangerous.
The overarching assumption is that, like James Bond (apologies to Carly Simon), "nobody does it better, makes me feel sad for the rest" than the FDA. That is a very bad assumption.
First, a prerequisite for being the "ultimate authority" in an information intensive endeavor such as pharmaceutical safety requires one be unmatched in the management of information and of information systems. Is there evidence that FDA is lacking in that regard?
At HCRenewal post "Computer debacle: a Broken down process at the agency - or beyond?" I commented on a WSJ article on familiar (to medical informaticists, that is) clinical IT mayhem at FDA:
Report on FDA Blasts New Effort To Track Drugs; Four-Year Delay Is Said To Hinder Safety Work; Agency Disputes Claims
Anna Wilde Mathews. Wall Street Journal. Mar 3, 2007. pg. A.1
The Food and Drug Administration has bungled its effort to build a new system for detecting the side effects of medicines after they go on the market, delaying its implementation by at least four years, according to a report commissioned by the agency itself.
As a result, the agency must continue to rely on its existing "dysfunctional" computer system as a primary tool for tracking the safety of medications sold in the U.S., according to the November 2006 report, which hasn't been made public.
A dysfunctional computer system? Computer systems do exactly what they're designed to do. Perhaps its designers and implementers were the ones who were "dysfunctional?"
The situation is "frustrating and undermining . . . the post- marketing drug safety work" of its staff "because they lack some of the basic tools they need to perform their jobs, e.g. a computing system that meets their requirements," says the report. It was prepared by the Breckenridge Institute, a research and consulting firm in Breckenridge, Colo.You'd think designing such a computer system were magic.
The FDA's drug-tracking system, called the Adverse Event Reporting System, consists of a database and other software and hardware that amass and help sift reports of potential side effects that have been filed by drug makers, doctors and others. The data are the FDA's main way to detect drug-related hazards, and can lead to changes in label warnings or even withdrawals of drugs from the market.
But, the report says, FDA safety experts waste time -- an average of 45 minutes per day -- dealing with the inefficiencies and snags caused by the current software. The Adverse Event Reporting System is overwhelmed by the growing volume of adverse-event reports, which exceeds 400,000 a year, the report says.
This report does not surprise me. It's hard enough to build effective HIT in a hospital due to the politics of IT and the bureaucracy. Performing that task in a huge, highly political burea-crazy such as a federal agency makes hospital IT look like child's play.
However, as a former big pharma middle manager (in the Research IT division of Merck Research Labs), I have seen reasonably effective efforts at the level of the pharmas, who are both better motivated to do so (profits and such) and better equipped (attractive salaries) than a federal agency. That speaks to the need to keep significant responsibility -- and liability -- for drug labeling within the pharmas themselves, and not allow preemption by a clumsy Big Brother.
Pharmas are closer to the data, even though they have their own problems (examples that cross both pharma and FDA follow) and a marketing-based reluctance to share adverse drug data freely and promptly. However, pushing the responsibility from pharma and the states to a federal agency that bungles the very technology needed to achieve credible results is akin to putting ultimate decision making of FedEx in the hands of the U.S. Postal Service.
Is there more evidence that making FDA the "ultimate authority" on adverse events issues might be insane in the real world in which we live?
Here is more from a paper I authored entitled "A Medical Informatics Grand Challenge: the EMR and Post-Marketing Drug Surveillance." The PDF is downloadable at this link. (Note: some of the links below may require updating or a search of archive.org):
In 2004 the U.S. government announced support for development and implementation of a nationwide, interoperable health information technology infrastructure to improve the quality and efficiency of health care. In the same year, several high-profile drug safety cases raised concerns about the ability of the Food and Drug Administration (FDA) to manage issues raised by adverse drug events [3].Concerns about FDA's ability to manage issues raised by adverse drug events? Is this a sign of an organization that should be considered a gold standard?
[3] United States Government Accountability Office, Washington, D.C. Drug Safety: Improvement Needed in FDA’s Postmarket Decision-making and Oversight Process. March 2006, p. 5.
More on this from the paper:
Outspoken critics on drug safety issues such as Dr. David Graham, a senior official in the FDA's Office of Drug Safety often come under fire for their views: “A Food and Drug Administration official [Graham] who sought to estimate the harm done to patients by side effects of the painkiller Vioxx said yesterday that his supervisors tried to suppress his conclusions, according to Sen. Charles Grassley (R-Iowa)." Since 1988, Graham has called for the removal of 12 drugs from pharmacy shelves, leading to 10 actual recalls of harmful drugs. Graham told Congress that FDA’s problems with ensuring drug safety were “immense in scope” and left the nation “virtually defenseless” against the chance that unsafe drugs will reach consumers [18].
[18] International Biopharmaceutical Association. Drug Recall: Effects on consumer confidence.
Still more confidence-inspiring material:
The [FDA's first annual Federal Register (FR) report on [drug] postmarketing studies] defines the status of 1,339 open manufacturers and 223 open postmarketing study commitments for biological products by 44 manufacturers. Of the open postmarketing drug studies, 820 (61%) are yet to be initiated; 285 (21%) are ongoing; 25 (2%) are delayed; 8 (1%) have been terminated before completion but the manufacturers have not submitted a final study report; and 201 (15%) have been either completed or terminated, and the FDA has received the final study report. Also in the drug area, annual reports for 289 (22%) of the open postmarketing commitments are overdue [32].
[32] 32. U.S. Food and Drug Administration. Federal Register Report and FDA Web Site on Postmarketing Studies, May 22, 2003.
So, the FDA is ineffectual at ensuring basic postmarket studies are conducted. Gold standard?
And more:
FDA lacks clear and effective processes for making decisions about, and providing management oversight of, postmarket safety issues. The process has been limited by a lack of clarity about how decisions are made and about organizational roles, insufficient oversight by management, and data constraints … There are weaknesses in the different types of data available to FDA, and FDA lacks authority to require certain studies and has resource limitations for obtaining data. Some of FDA's initiatives, such as the establishment of a Drug Safety Oversight Board, a draft policy on major postmarket decision making, and the identification of new data sources, may improve the postmarket safety decision-making process, but will not address all gaps … FDA is taking steps to identify additional data sources, but data constraints remain [40].
[40] United States Government Accountability Office, Washington, D.C. Drug Safety: Improvement Needed in FDA’s Postmarket Decision-making and Oversight Process, March 2006, Highlights
On attempts at corrective action:
FDA itself has a history since the 1950’s of founding committees and establishing and disestablishing multiple new research organizations (centers, bureaus and least one institute) to make major changes in the organization and management of its scientific endeavors. Most of these repetitive efforts failed [42].Now, on to another issue with FDA. Is staring idiocy directly in the face a "teachable moment" that can be used to extrapolate the existence of more severe problems?
[42] Baciu A, Stratton K, Burke S, Editors. The Future of Drug Safety: Promoting and Protecting the Health of the Public. Committee on the Assessment of the US Drug Safety System, Board on Population Health and Public Health Practice (BPH), Institute of Medicine, 2006, p. 104.
I believe it is.
My personal interaction with a senior FDA official is documented at "FDA's hefty bonuses seek to retain workers." I reported my experience at a late 2004 Merck interview with the FDA's former Deputy Director of the Office of Drug Safety at CDER, Dr. Martin Himmel, who had come to Merck from FDA and taken the position of Executive Director in Clinical Risk Management & Safety Surveillance, Merck Research Labs.
Unemployed since Merck's mass layoffs of 4,400 souls in late 2003, I had interviewed with Himmel's underlings in Clinical Risk Management & Safety Surveillance, and had shown them my prior work in building innovative tools and techniques to allow scientists much more fluid and dynamic access to large biomedical datasets, and to perform ad hoc analytics upon that data firsthand. The scientists and clinicians in the department viewed my work highly favorably, and informed me about significant problems with data access they were experiencing.
Those problems included a somewhat unwieldy structure to their adverse events database, and a dependence on overworked IT personnel to run queries and abstract data from the large database, often providing the scientists with paper results which were next to useless for advanced work.
I came to Dr. Himmel with the highest of recommendations from his staff. I proceeded to show him my work, including an invasive cardiology information system of my design, in use for adverse events detection and analysis, PI, QA, benchmarking, etc., at one of the largest centers in the region (performing more than 6000 procedures annually) along with acclaim the system had received from experts at the national organization for Cardiac Angiography and Interventions:
"We believe your efforts in [cardiac laboratory database development] are exceptional compared with the current norm in most laboratories and we strongly support the continued efforts to develop this system within Christiana Care."
Report of Consultation Visit, Laboratory Survey Committee of the Society of Cardiac Angiography and Interventions, Gregory Dehmer, MD, Patrick Scanlon, MD, Oct. 1999).
I also brought with a demo of the Saudi Arabia-Yale Clinical Birth Defects information system (SAYGR) I built in an international collaboration with the King Faisal Specialist Hospital & Research Centre in Riyadh. SAYGR employed novel techniques I invented at Yale to allow capture and ad hoc analytics of clinical, genetic, genealogical, drug and chemical exposure (e.g., chem warfare) data, and other data types by non-computer expert scientists and clinicians.
The work I'd done in building these systems was directly and immediately relevant towards building of drug adverse events databases and analytical tools, but Dr. Himmel simply didn't see it.
He cut me off after only about ten minutes and dryly observed that "we don't need Medical Informatics here."
At that, I realized I was staring idiocy in the face. Since it's pointless to argue with idiocy, I got up, said goodbye and left. This from a former top official in drug safety at CDER, I thought? Unbelievable.
It should be noted that the Institute of Medicine of the National Academies, as I observed at "IOM gets it regarding Medical Informatics", recommends:
... that CDER [FDA's Center for Drug Evaluation and Research] build internal epidemiologic and informatics capacity in order to improve the postmarket assessment of drugs. In recognition of the limitations in human resources in the current employment market to meet this role, a combination of advancing professional skills through continuing education and support for academic training programs is needed.
and that
Informatics experts should track progress on the national health-information infrastructure, look for opportunities to gather information about drug safety and efficacy after approval, coordinate partnerships with external groups to study the use of electronic health records for [drug] adverse event surveillance, participate in FDA’s already strong role in setting national standards and track the development of tools for data analysis in industry and academe, and encourage the incorporation of the tools into FDA practice where appropriate.
I had been told by a former top leader at CDER that he, in effect, disagreed with this assessment.
This very same person was a leader at FDA in the time frame of Ms. Levine's travails.
Again, the industry wants the FDA to be considered the "ultimate authority" on drug adverse events?
We have evidence for IT disarray, noted defects in management of drug adverse events responsibilities, and reactionary leadership in the Office of Drug Safety at CDER itself.
As noted in the NYT editorial:
... And that is the greater point. When Congress revised the federal law governing the F.D.A. in 2007, drug companies wanted, but did not get, a provision shielding them from this sort of lawsuit. The drug industry and its administration allies now want the court to ignore the absence of express legal language and grant drug companies immunity based on a phony assertion that state lawsuits improperly usurp federal regulatory authority.
I would state the true "greater point" a little differently. The federal regulator in this case is an emperor that stands naked and tin-plated. Considering the FDA as "a gold standard" that negates the jurisdiction of the states not only reduces the responsibility and liability of pharmaceutical companies, but also is cavalier on its face considering the FDA's troubles.
As is noted by the NYT:
Far from usurping the F.D.A.’s power, litigation aimed at holding drug companies liable for problems like those in this case complement the agency’s efforts to protect the public. For many years the F.D.A. welcomed state failure-to-warn suits as reinforcing those efforts; two former commissioners, David Kessler and Donald Kennedy, made that point in a brief in the case.
These commissioners apparently understood the limitations of the FDA and that FDA efforts needed to be complemented (not compl-i-mented!) in that manner to protect the public.
Finally, a commenter to the NYT editorial, Arthur Taub, MD PhD, New Haven, CT, wrote that:
"It is essential that the authority of the FDA be maintained, and that license is not given in 50 separate jurisdictions for uncontrolled litigation and supplementary "deep pocket" awards against industry."
Irrespective of Dr. Taub's role as expert witness for hire (I have not researched if he has represented pharmas), I would say instead that it's essential the authority of the FDA be challenged relentlessly, until the agency can be relied upon to stop screwing up fundamentals like clinical IT and adverse events data management. Until then the states should hold their ground against a federal intrusion by the Keystone Kops.
It is my hope the Supreme Court will examine the evidence critically and agree with this assessment.
-- SS
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