The Articles in the Category cover a vast range of history not only in our country but in the world as well. The category is entitled “How We Sold Our Soul”. In many cases our history has hinged on compromises being made by the powers at be. They say hind-sight is 20/20, which is why I am discussing these land mark decisions in this manner. The people that made these decisions in many cases thought they were doing the right thing. However in some instances they were made for expediency and little thought was given to the moral ramifications and the fallout that would result from them. I hope you enjoy these articles. The initial plan is to discuss 10 compromises, but as time progresses I am sure that number will increase.
Misplaced Trust: Why FDA Approval Doesn’t Guarantee Drug Safety
When 37-year-old Timothy “Woody” Witczak’s doctor gave him a few Zoloft (sertraline) samples to help him sleep in 2003, neither he nor his wife, Kim, was alarmed.
“Woody and I never once questioned the drug. Why would we? Zoloft is FDA-approved, given to him by his doctor, and advertised and sold as safe and effective,” Kim told Drugwatch.
A couple of days later, Woody started experiencing side effects including diarrhea, night sweats, trembling hands, nightmares and worsening anxiety. Woody became highly agitated and irritable. His insomnia worsened. He described feeling like his head was outside his body.
Once again, the couple sought the help of their doctor.
“He told us that we should give [Zoloft] four to six weeks to start working,” Kim said.
Five weeks later, Woody — a happily married, energetic, compassionate and cheerful man with a successful career — was dead. He had hung himself in the garage.
“We were shocked at the suicide,” Kim said. “He had no history of depression or mental illness. That night my brother-in-law went home and Googled Zoloft and suicide. He was shocked to learn that the FDA had hearings on Prozac and suicide back in 1991. He told me, ‘I think I know what killed Woody.’”
The family discovered Zoloft, an FDA-approved antidepressant, led to Woody’s tragic death.
Unfortunately, what Woody’s family didn’t know is the FDA’s approval process may favor drug companies over consumers — and FDA-approval does not guarantee safety. In fact, Big Pharma actually pays for the majority of drug safety reviews, provides the FDA with safety data for the review and has the option to have drugs approved faster with fewer clinical trials.
The Birth of a New Drug
“FDA approval is based on evidence — provided by the company that makes the medical product — that the benefits of the product outweigh the risks for most patients for a specific use. It doesn’t necessarily mean the product is safe.”Diana Zuckerman, president of the National Center for Health Research
A new drug takes several steps before it makes its way into a consumer’s medicine cabinet. Unlike medical devices that are cleared for sale without extensive testing if a similar device is already on the market, drugs must go through clinical trials before they are available to consumers.
While the process of approving a new drug may seem thorough on paper, critics say it assumes the world is a perfectly controlled environment. Also, clinical trials have short timeframes and can’t thoroughly determine safety.
“When a new drug is first approved by the FDA, it typically has only been tested in several hundred to a few thousands patients in carefully controlled clinical trials that last several weeks to several months and that exclude many types of patients who will end up being prescribed the drug,” Michael A. Carome, Public Citizen’s Health Research Group director, told Drugwatch. “As a result, only the most common types of serious adverse events will be detected prior to FDA approval.”
In fact, the FDA calls drug approval a “balancing act” between acceptable risks and benefits on its website. But did Woody Witczak and his family know about this balancing act before he took Zoloft?
“No cautionary warning was given to him or me,” Kim Witczak said. “In fact, the 3-week Pfizer-supplied sample pack that Woody came home with automatically doubled the dose unbeknownst to him from 25 to 50 mgs after week one.”
Essentially, consumers like Woody Witczak and his family are playing the odds when they take a new drug.
“Even though data from human trials are analyzed by a team of experts before a drug is approved, it can be impossible to anticipate all bad reactions — especially very rare safety risks — unless they had also happened with use of a similar drug,” the agency admitted on its website.
The entity responsible for reviewing news drugs is the FDA’s Center for Drug Evaluation and Research (CDER). The CDER breaks down the process into phases: preclinical, clinical, and New Drug Application (NDA) review.
After a drug company discovers a new compound, it starts the FDA-approval process. The preclinical phase is the drug maker’s discovery and screening phase.
First, it must test the drug on animals to determine its toxicity level. Researchers find out basic safety and efficacy information about the new drug. After it gathers initial data, the drug company submits an Investigational New Drug (IND) application to the FDA. The IND includes basic facts about the drug and a plan for human testing.
After the FDA verifies the planned clinical trials will not put human subjects at unreasonable risk, it moves the drug to the next phase.
2. Clinical Study Phase
The clinical study phase is when the drug maker conducts tests on human subjects. Clinical trials go through three phases.
Three Phases of Clinical Trials
Phase 1: The goal of this phase is to discover what the drug’s most frequent side effects are. Usually about 20 to 80 participants enroll in this phase. Phase 2: The goal of this phase is to discover the drug’s effectiveness. Researchers gather preliminary data on how the drug works in people with a certain disease or condition. Researchers compare the drug against placebo or another drug. Short-term side effects are studied. Usually a few hundred people participate in Phase 2 studies. Phase 3: Phase 3 continues to test safety and efficacy in a larger number of people on different doses and in combination with a few drugs. More than 1,000 patients typically participate in Phase 3 trials.
3. New Drug Application (NDA) Review
Once clinical trials are finished, the drug company submits a New Drug Application. Then, the drug company submits an official NDA that includes animal and human data plus information on how the drug will be manufactured.
The FDA has 60 days to review the NDA before officially filing it. After the FDA files the NDA, it reviews all the research submitted by the drug company for safety and effectiveness. Next, it reviews the drug’s proposed label to ensure health care professionals and consumers get the right information. Finally, the FDA inspects the facility where the drug company will manufacture the drug.
Now, the FDA has the information it needs to decide whether to approve a drug or issue a rejection letter.
New Drug Research and Development Cost and Controversy
The amount a drug company spends to get a new drug on the market is a constant source of debate. Industry claims it is in the billions. It frequently uses this number to justify charging Americans higher drug prices.
In 2011, Donald W. Light and Rebecca Warburton challenged that figure.
Light is a professor of comparative health care policy at the University of Medicine and Dentistry of New Jersey and a founding fellow of the Center for Bioethics at the University of Pennsylvania, and Warburton is a professor of health economics at the University of Victoria in Canada.
According to Light and Warburton, $56 million is the net cost to companies after taxpayers cover 50 percent of research and development expenses for each new drug they develop. They say drug companies get a large portion of costs paid back from write-offs, National Institutes of Health grants and other forms of creative accounting.
Fast Track to Adverse Events
“For some drugs, safety concerns are only discovered after they have been on the market, sometimes for several years. The U.S. Food and Drug Administration (FDA) has adopted several policies that could increase the likelihood of approving a potentially unsafe medication.”Saluja et Al., The International Journal of Health Services, June 14, 2016
Big Pharma is fond of criticizing the FDA for not approving drugs quickly enough and depriving patients of life-saving medications. In reality, the FDA approves drugs faster than its counterparts in Europe, Canada and Japan. In the 1980s and 1990s, the FDA began new programs that fast-tracked the approval of certain drugs.
While this might mean some patients benefit from new therapies, the speed at which the FDA approves drugs can have dangerous consequences.
In Witczak’s case, no one told the family that FDA reviewers were pressured to speed up the Zoloft’s approval in the 90s or that the drug’s clinical trial data was questionable.
Dr. Paul Leber, then director of FDA’s Division of Neuropharmacological Drug Products, knew there were problems with Zoloft’s efficacy data in 1991. But he “assured Pfizer that he thought he could convince the Committee that the studies were sufficient to recommend approval,” according to legal documents that surfaced in 2013.
Each year, more than 2 million Americans suffer serious adverse reactions from FDA-approved drugs like Zoloft. These side effects lead to about 100,000 deaths, according to a 2016 study published in The International Journal of Health Services by Sonali Saluja and colleagues.
“This problem is serious. The study by Saluja et al. shows that over 100 million prescriptions were issued for drugs that had to be withdrawn from the market because they proved to be unsafe,” Dr. Don McCanne wrote in response to the study on Physicians for a National Health Program. “This is particularly tragic when it is a drug that never should have been on the market in the first place.”
Study authors found that many safety problems only emerge after the FDA approves drugs and blamed the problems on fast-track drug approval programs.
“Indeed, in the first 16 years after approval, 27 market withdrawals and serious new safety warnings — so-called black box warnings (BBWs) — are issued for every 100 newly introduced drugs,” Saluja and colleagues wrote.
In Europe, regulatory agencies require more review processes for safety and efficacy before insurance plans will even pay for the drugs.
Accelerated Approval and Fast Track Programs
During the NDA Review process, drug companies may apply for Accelerated Approval or a Fast Track program.
- Accelerated Approval allows earlier approval of drugs that fill an unmet medical need and uses “surrogate endpoints” to determine effectiveness. A surrogate endpoint is an indicator (for example, blood tests, X-rays) used to tell if a treatment works but does not necessarily guarantee it works. For example, if a cancer drug seems to make a tumor smaller, the FDA concludes it is effective even if there is no clinical trial to prove the drug actually extends life expectancy.
- The Fast Track Program reduces approval time for drugs that treat serious or life-threatening diseases. Drugmakers can submit portions of the application instead of providing the information all at once.
Newer and Faster Does not Always Equal Better
Not only are these new drugs risky, most are also no better than previous drugs, according to Donald W. Light and researchers at the Edmond J. Safra Center for Ethics at Harvard University.
“Public, independent advisory teams of physicians and pharmacists in several countries found over 90 percent of new drugs approved by the FDA and the European Medicines Agency (EMA) offer few or no advantages over existing drugs to offset their risks of serious harm,” Light wrote about the findings in a 2015 post on a Health Affairs Blog.
Holes in the FDA-approval Process
“The FDA is supposedly a watchdog agency mandated to protect the public from dangerous and ineffective drugs. In fact, the FDA is ineffective and dangerous to the public.”Alexander Bingham, Clinical Psychiatrist and Professor at John F. Kennedy University
While fast-track programs may compromise safety, the FDA’s regular approval process is also not without its own issues. For instance, clinical trials the agency uses to determine safety and efficacy also have several limitations, according to Consumer Reports.
According to a 2003 survey quoted by Consumer Reports, FDA reviewers felt rushed and pressured to approve medications. There are also some studies that found the faster a drug was reviewed, the greater the chance for adverse events surfacing after the drug hits the market.
Mary K. Olson of Tulane University conducted one study in 2003.
Each 10-month reduction in review time period
- An 18 percent increase of serious adverse reactions
- An 11 percent increase of drug-related hospitalizations
- A 7.2 percent increase of drug-related deaths
The FDA doesn’t always apply the same criteria to all drugs, either. For instance, a study published in JAMA in 2014 by Nicholas S. Downing and colleagues of Yale University School of Medicine found:
As of 2014
- 37 percent of approved drugs were only backed by a single study
- 45 percent of all drugs were approved on “surrogate endpoints”
- 68 percent compared new drugs only to placebos, which this means they determined something was better than nothing — not that the drug was better than another drug
“We’re talking about families going into debt so their loved one can get access to a medication,” Joseph Ross, one of the study authors, told USA Today. “Maybe if they know that a drug doesn’t prolong life, they will be less likely to mortgage their home. People should have access to the full spectrum of information.”
Consumer Reports Issues with FDA Approvals
In 2015, Consumer Reports detailed several issues with the FDA’s pre and post approval processes.
Preapproval issues with FDA drug reviews:
- Clinical trials are too small to give a proper estimation of adverse events.
- Trials only last for a few months, but some dangerous adverse events occur after several years.
- Most trials use specially selected, healthy participants to show that the drug works, but this doesn’t reflect its use in the real world in a bigger, sicker population.
- Doctors may prescribe the drug for off-label uses — uses not studied or approved by the FDA.
- Surrogate endpoints provide a misleading picture of how a drug works.
Post-Approval issues with FDA drug reviews:
- Adverse events are not always reported because reporting is voluntary.
- The FDA may request post-marketing studies to follow up on safety concerns, but drug makers don’t always do them.
- Drugmakers don’t always publish clinical trials with unfavorable results. For example, Merck only published studies showing Vioxx (rofecoxib) patients tolerated the drug well. Several years later it revealed data showing people were having heart attacks.
- The U.S. has no system to regularly scan and analyze large databases of patients for adverse events.
Does the FDA Work for Big Pharma?
“User fees fundamentally changed the relationship between the FDA and the pharmaceutical industry such that the agency now views industry as a partner and a client, rather than a regulated entity.”Michael A. Carome, Director, Public Citizen’s Health Research Group
While taxpayers still provide about one third of the FDA’s funding, the agency receives the majority of its drug-review funding from Big Pharma — the very industry it should be regulating. It’s a little-known fact to most Americans, and it raises red flags for a number of consumer groups.
“Taxpayers are also paying for agency [funding], but we’re not treated as the customers — the companies are,” Zuckerman said.
Under the Prescription Drug Use Fee Act (PDUFA) of 1992, drug companies pay user fees to get drugs approved. Initially, Congress passed PDUFA to provide a budget to hire more medical scientists and researchers to deal with the drug application load.
Over time, the law expanded. Since 1992, several reauthorizations of PDUFA further weakened the standards for approving drugs. For example, it allowed companies to use one trial instead of two to approve a drug in some cases.
The fact that Big Pharma pays a substantial amount of FDA’s operating costs should give anyone pause, according to critics. This is a big conflict of interest.
“Approximately two-thirds of the agency’s budget for review of drug products is now funded by the pharmaceutical industry,” Carome said. “As a result, speed of review and approval too often take precedence over protecting public health and ensuring that drugs are safe and effective.”
With Big Pharma footing the bill, monitoring side effects may be lower in importance than approving drugs. Professor Donald W. Light estimates the FDA — an institution developed to protect the public from unsafe and ineffective drugs — only spends about 10 percent of its budget monitoring harmful side effects.
Under the White House’s proposed 2018 budget, user fees will grow more than double. This could potentially hike up the influence drug companies already have. The government also plans to decrease federal funding of the U.S. Department of Health and Human Services — the FDA’s parent agency, according to the budget outline.
This could potentially make the FDA more dependent on drug companies for funding.
FDA Does Not Conduct Its Own Studies
“All of this is going on behind the scenes while the average, every day person like Woody goes in to their doctor and puts their faith and trust in their doctor. They trust that they are being given a drug, device, or treatment that is ‘safe and effective’ which has been approved by the FDA.”Kim Witczak, Patient Advocate
Another fact that Americans should know is that the FDA does not conduct its own independent studies on drug safety and effectiveness when approving drugs. It relies on data and studies provided by the manufacturers.
This means the FDA can only base its approval or denial on the information the drug company provides, and drug companies may cherry-pick the data they want the FDA to see, according to Dr. Alexander Bingham.
Bingham is a clinical psychologist at Full Spectrum Progressive Psychology and teaches psychological research methods and phenomenological research at John F. Kennedy University in San Jose, California. He did graduate research on the approval of Prozac and says the drug’s approval process is a prime example of manipulating studies.
“Eli Lilly Pharmaceuticals conducted 20 studies to prove the antidepressant effect of fluoxetine hydrochloride, more popularly known as Prozac. Only three studies were ever submitted to the FDA for approval due to 17 outright failures.”Dr. Alexander Bingham, Clinical Psychologist and Professor of Psychological Research at John F. Kennedy University
“By its own report, the FDA challenged the validity of all three studies citing both procedural and statistic errors and denied Lilly approval for Prozac twice,” Bingham told Drugwatch.com.
After Lilly sent in a third data submission, the FDA finally approved the drug. But, there were no new trials, “only statistical manipulation and repackaging of existing data to create more favorable results,” Bingham said.
In order to obtain this information, Bingham had to request copies of documents through the Freedom of Information Act. Even then, most of the information was blacked out when he received it.
Manipulating study data is more prevalent than the public knows.
Research fellows at the Edmond J. Safra Center for Ethics at Harvard University, including Donald W. Light, investigated institutional corruption in the pharmaceutical industry. They found pharmaceutical companies use legal ways to manipulate “FDA rules to generate evidence that their new drugs are more effective and less harmful than unbiased studies would show.”
Drug companies hire a team of writers, statisticians and editors to “repackage” trial results to be favorable to their drugs. Whether the FDA acknowledges this practice and allows it is anybody’s guess.
After Woody’s death, Kim Witczak saw the flaws and corruption in the system firsthand.
“All of this is going on behind the scenes while the average, every day person like Woody goes in to their doctor and puts their faith and trust in their doctor,” she said. “They trust that they are being given a drug, device, or treatment that is ‘safe and effective’ which has been approved by the FDA.”
Risky FDA-approved Drugs Lead to Recalls
“This problem is serious. The study by Saluja et al. shows that over 100 million prescriptions were issued for drugs that had to be withdrawn from the market because they proved to be unsafe.”Dr. Don McCanne in response to the study on physicians for a national health program
History shows a number of FDA-approved drugs that went on to cause serious adverse events. Many patients were unaware that there was even a risk. Later the FDA announced recalls for these products.
According to Saluja and colleagues’ 2016 study, the median time from FDA approval to removal from the market is five years. But some are on the market for decades before removal, placing several million people at risk.
Some Notable FDA-Approved Drugs Later Recalled for Safety Risks Include:
- ACCUTANE (ISOTRETINOIN) Treats acne. Approved in 1982, recalled for birth defects, bowel disease and suicidal tendencies in 2009.
- DES (DIETHYLSTILBESTROL)Prevents miscarriages. Approved in 1940, recalled in 1971 for cervical cancer, birth defects, risk of breast cancer and infertility in children and grandchildren.
- VIOXX (ROFECOXIB) Painkiller. Approved in 1999, recalled in 2004 for increased risk of heart attack and stroke after nearly 28,000 heart attacks and cardiac deaths.
- MERIDIA (SIBUTRAMINE)Appetite suppressant. Approved in 1997, recalled in 2010 for increased cardiovascular and stroke risk.
- REZULIN (TROGLITAZONE)Treats Type 2 diabetes. Approved in 1997, recalled in 2000 for liver failure and deaths. Other drugs in the same class still available include Actos (pioglitazone).
- SELACRYN (TIENILIC ACID)Blood pressure drug. Approved in 1979, recalled in 1982 for hepatitis, deaths and severe liver and kidney damage.
FDA’s Recall Notification System Needs Improvement
Not only does the FDA have issues with approving drugs with incomplete safety studies, it also takes far too long to identify dangerous drugs that make it on the market and warn the public.
A 2012 study from researchers at Brigham and Women’s Hospital in Boston found the FDA’s recall system isn’t enough to warn health care providers or patients. The study published in the Archives of Internal Medicine found the FDA only issued notices for about half of the Class I recalls from 2004 to 2011. Class I recalls are the most serious and typically cause death or serious injury.
“The FDA offers this communication service, and we anticipate that a lot of providers may rely on it and in doing so may not be getting the information they need when drugs are recalled,” Joshua Gagne, an epidemiologist at Brigham and Women’s Hospital and one of the authors of the study told ABC News.
While the FDA may suggest or request a recall, it has no legal authority to enforce a drug recall. Ultimately, manufacturers are responsible for pulling dangerous products off the market. This weakens the FDA’s authority to ensure safety.
The number of drug recalls surged in recent years, according to FDA data made public in 2014. Recalls nearly tripled from 499 in 2012 to 1,225 in 2013. The FDA classified 1,031 of the 2013 recalls as Class II — the “product may cause temporary or medically reversible adverse health consequences.”
In February 2017, Democratic Congresswoman Rosa DeLauro of Connecticut introduced a new bill called The Recall Unsafe Drugs Act that would allow the FDA to require drug companies to recall a product.
“As it stands, the FDA would have to go through an arduous legal process to take action against manufacturers …This is unacceptable and threatens the health and safety of American families. The Recall Unsafe Drugs Act will enable the FDA to step in and issue a mandatory recall of drugs that have been found to cause serious health consequences or death,” DeLauro told the Regulatory Affairs Professionals Society.
FDA Preemption Laws and Wyeth v. Levine
“Manufacturers remain the master of their labels even after FDA approval, and there are clear pathways through which a brand-name drug manufacturer can make changes to their label without FDA approval.”Judge Eldon Fallon, Wyeth V. Levine
The FDA’s drug approval process may let dangerous drugs onto the market, and drug companies may also use it to escape liability when a bad drug hurts people by claiming FDA preemption.
When drugs injure people, one of the only avenues for victims to get justice is to file a lawsuit. When Witczak killed himself allegedly because Zoloft had no warnings for suicide, Kim Witczak sued Pfizer for failing to warn them of the risk. It was a way for her to bring awareness to the issue of safety and keep other families from suffering.
FDA preemption laws threaten consumer’s rights to hold drug companies accountable for failing to warn.
How Preemption laws work to protect drug companies
- When a drug gains FDA approval, the drug and it’s label – including the warnings and side effects – are approved as-is.
- Someone develops a severe side effect that has been linked to the drug but was not included on the original warning label.
- When a person sues, the drug company claims the FDA’s approval of the drug shields them from liability.
According to FDA preemption theory, an FDA-approved, brand-name drug is exempt from liability because the agency approved the warning label as is. Preemption means that federal law — in this case the Food, Drug and Cosmetic Act that authorizes the FDA to approve the release of new drugs into the market — should trump a state’s failure to warn law.
Drug manufacturers claim they cannot make a label change without FDA approval. They say the FDA’s red tape prevents them from adding label changes to warn patients and doctors. Therefore, this allows them to get away without adding warnings.
But a very important 2009 U.S. Supreme Court ruling in a historic case called Wyeth v. Levine found that FDA approval of a drug does not shield the manufacturer from liability under state law.
Wyeth v. Levine
Diana Levine sued Wyeth after she said its anti-nausea drug Phenergan caused her to develop gangrene in her hand and forearm. She had to have the infected limb amputated. In her claim, she said Wyeth failed to warn her about the gangrene risk.
Wyeth appealed, using FDA preemption, and argued that its label met the requirements of the FDA, a federal agency. So, it should not be held liable under Vermont’s state law.
The trial court and Supreme Court of Vermont ruled that the FDA requirements do not supersede state law.
The industry lobbying group Pharmaceutical Research and Manufacturers of America (PhRMA) issued a statement in support of preemption following the ruling.
“We continue to believe that the expert scientists and medical professionals at the Food and Drug Administration (FDA) are in the best position to evaluate voluminous information about a medicine’s benefits and risks and to determine which safety information to include in the drug label.”Ken Johnson, Former Senior Vice President, Pharmaceutical Research and Manufacturers of America
Like Wyeth, Pfizer also attempted to argue preemption in Kim Witczak’s Zoloft case.
Pfizer claimed that the state’s failure-to-warn law upon which Witczak’s lawsuit relied conflicted with the FDA’s requirements for labels. The company argued it should not be held liable for failing to warn about suicide risk. It requested that the court throw out the case. Judge James M. Rosenbaum denied Pfizer’s request in 2005.
“FDA regulations allow drug manufacturers to strengthen warning labels ‘in the interest of drug safety’ at any time without FDA pre-approval precisely so that the warnings can be ‘placed into effect at the earliest possible time’ and ‘to enable prompt adoption of such changes,’” Rosenbaum said.
A more recent example of the preemption defense occurred in Xarelto (rivaroxaban) uncontrolled bleeding litigation. Plaintiffs claim the drug’s label does not adequately warn about the bleeding risk. Right before the bellwether trials in April 2017, Janssen Pharmaceuticals and Bayer argued that FDA regulations prevented them from updating labels or creating more tailored dosing guidelines.
U.S. District Judge Eldon Fallon denied Janssen and Bayer’s motion to have some cases thrown out based on preemption.
“Manufacturers remain the master of their labels even after FDA approval, and there are clear pathways through which a brand-name drug manufacturer can make changes to their label without FDA approval,” he said in his order.
Improving the FDA’s Approval Process
“Taxpayers are paying for the agency, but we’re not treated as the customers — the companies are.”Diana Zuckerman, president, National Center for Health Research
While pointing out what could be wrong with the FDA might seem easy, fixing decades of broken practices is more complicated.
Critics and consumer advocates say one of the biggest problems is the user fees and the agency treating drug companies like its customers. The FDA should have more independent sources of independent data.
“The FDA’s current drug approval process is too dependent on the quality and integrity of research paid for the companies and too focused on approving new drugs quickly,” said Zuckerman. “Taxpayers are paying for the agency, but we’re not treated as the customers — the companies are.”
What is sorely needed are more independent voices, she said. FDA Advisory Committee meetings should include independent experts with no ties to pharmaceutical companies. These experts would help the FDA require more meaningful safety studies.
“If there is a safety concern or controversy, the FDA should welcome debates of science in an open forum,” added Kim Witczak. “For example, the antidepressant issue would have greatly benefited had this happened. Instead, those leading global experts with differing viewpoints were only given three minutes in open public forum.”
Witczak said that more independent patient’s views should make their way into the FDA’s process. Currently, most of the opinions they hear are from patient groups funded by pharmaceutical companies.
One example of this questionable process was the approval for Addyi (flibanserin), a drug for low sexual desire in women. Boehringer Ingelheim stopped working on the drug in 2010 after the FDA gave it a negative evaluation. Sprout Pharmaceuticals bought the drug and paid patients to plead to the FDA for approval. Critics said the agency approved the drug on the same questionable data after pressure from these industry-funded patients.
According to Carome, the director of Public Citizen’s Health Research Group, the FDA also approves drugs even when there are glaring safety issues. The agency then asks drug companies to conduct follow-up studies. In the meantime, the FDA exposes the public to the potentially dangerous drug.
“A better approach to protect patients from harm would be not to approve the products, but instead demand additional trials prior to approval,” Carome said.
The Aftermath of Losing a Loved One
“It was too late for our family, but if just one family is informed, then Woody’s life and death made a difference.”Kim Witczak, Patient Advocate
Witczak’s journey after losing her husband led her to a path of activism that includes her role as a consumer representative on the FDA Psychopharmacologic Drugs Advisory Committee.
“I was out of town on business when I got a call from my dad telling me that Woody, my husband of almost 10 years, was found hanging from the rafters of our garage, dead at age 37,” Witczak said, recalling that fateful day nearly 14 years ago. “Woody, my best friend, the guy I was supposed to have a family and grow old with was gone.”
Her husband’s story echoes those of others harmed by FDA-approved drugs. When Kim started fighting for patient’s rights, it was for Woody. But, she realized the issue was bigger.
“The journey for the truth has taken me to the FDA, U.S. Department of Health and Human Services (HHS), Congress, the courts and media,” Witczak continued. “I work with a huge network of patient safety activists across the country that work on a variety of issues. Many of them came into this work as a result of a harm or adverse experience.”
Witczak stresses education. She says consumers should challenge their physicians and find out all they can about a drug. The FDA also needs more authority to compel recalls and police drug and device companies.
“It was too late for our family,” she said. “But if just one family is informed, then Woody’s life and death made a difference.”
What’s Wrong with the FDA?
If Robert Califf, the White House nominee for commissioner of the U.S. Food and Drug Administration, is confirmed by the Senate, he’ll take the reins of an agency with its reputation in tatters. Once revered as the global leader in drug regulation, the FDA has approved one bad drug and medical device after another over the past 30 years, leaving staff demoralized and overseas regulators scratching their heads. Meanwhile, about a third of Americans refuse to get vaccinated for COVID-19, in part because they distrust government and scientific institutions.
In the case of the FDA, at least some of that mistrust is deserved even if the COVID vaccines are generally safe. (We’ve both taken them.) The most recent FDA disaster erupted in June, when officials approved the Alzheimer’s drug Aduhelm over the objections of the agency’s biostatistician and an 11-member committee of expert advisers. The data submitted by Biogen, the drug’s manufacturer, failed to show that Aduhelm is effective. It also poses a significant risk of harm, including brain bleeds and swelling in about a third of test subjects. Agency higher-ups decided to overlook these shortcomings and put the drug on a fast track for approval.
Three members of the FDA advisory committee promptly quit in protest over the Aduhelm decision, and multiple hospital systems have refused to administer the wildly expensive drug, fearing it doesn’t work, will hurt patients, and will break their budgets. (The drug is priced at $28,000 a year per patient.) Thanks to its eye-popping price, the Centers for Medicare and Medicaid Services raised its premiums by 14.5 percent, the largest increase in its history, half of which was to accommodate this one drug. It’s no wonder that European regulators gave Aduhelm a thumbs-down, and Japan appears ready to follow suit. On January 11, the CMS announced its preliminary decision not to pay for Aduhelm except for patients enrolled in high-quality clinical trials, saying “important questions” remain about the drug. That decision should be finalized later this year.
The Aduhelm debacle and other FDA blunders can be traced to declining scientific standards at the agency and increasingly cozy ties with the companies it regulates. Multiple FDA officials have passed through the revolving door from industry to government and back again, but not before leaving behind regulations and controversial approval decisions that benefited manufacturers. In a 2016 study, most officials who left the FDA after reviewing cancer drugs for the agency went to work for biotech companies.
Aside from advancing their careers, FDA higher-ups have another powerful incentive to make decisions that serve corporations over patients: the agency’s heavy dependence on industry funding. In 2019, approximately 61 percent of the FDA’s $2.5 billion budget for drug approvals (including biotech drugs) came from user fees charged to manufacturers. Those fees are mandated by a 1992 law passed by Congress to speed up drug approvals.
But speed can lead to disaster: The pain medicine Vioxx was fast-tracked for approval in 1999. By the time it had been pulled from the market four years later, it had killed an estimated 60,000 Americans. One-third of all new drugs approved since 2000 have turned out to have safety problems. Those approved through the fast-track process, or “accelerated approval pathway,” are even more likely to be withdrawn or slapped with mandatory warnings about serious complications, including death. “Our current system for testing drugs before they go on the market is very weak,” says Rita Redberg, a cardiologist at the University of California at San Francisco and editor in chief of the medical journal JAMA Internal Medicine.
Patients and the public need radical reform at the FDA and a commissioner who will champion a return to sound science and loosening, if not cutting, the agency’s financial ties to the companies it is supposed to be regulating.
Unfortunately, Robert Califf is probably not that commissioner. The 71-year-old cardiologist previously served as FDA commissioner under President Barack Obama from February 2016 to January 2017, after being passed over for the job in 2009 because he was widely seen as too close to the drug industry. Despite conflicts of interest that included financial relationships with 23 companies, Califf sailed through confirmation as FDA commissioner with only a handful of senators objecting to his industry ties.
This time may be different. On January 14, Califf’s nomination was sent to the full Senate following a 13–8 vote in the Committee on Health, Education, Labor and Pensions. Democrat Maggie Hassan of New Hampshire and independent Bernie Sanders of Vermont voted against Califf, while four Republican members supported him. Three more Democratic senators have said they’ll vote against confirming Califf when it comes to the floor: Ed Markey of Massachusetts, Richard Blumenthal of Connecticut, and Joe Manchin of West Virginia. Each, like Hassan, has expressed concern about the FDA’s handling of the opioid crisis. Senate Democratic leaders will need at least five Republican votes, which would give Vice President Kamala Harris the tie-breaking vote to confirm the nominee.
During his brief tenure as FDA commissioner in the Obama administration, Califf did little to slow the flood of useless or dangerous drugs. Notably, he supported the controversial decision to approve eteplirsen (brand name Exondys 51), a drug for the rare but fatal muscle-wasting disease Duchenne muscular dystrophy. Studies of eteplirsen have never shown that it slows, much less stops, the progression of the disease. Califf passed the buck and left the final decision to Janet Woodcock, then head of the FDA’s Center for Drug Evaluation and Research. Woodcock is currently acting FDA commissioner and has championed the drug internally.
Califf has only grown closer to industry since the Obama years. According to disclosure documents filed in July 2020, his ties span more than two dozen drug and biotech companies. He was paid $2.7 million by Verily Life Sciences, the biomedical research organization operated by Alphabet Inc., and he has a massive stock portfolio with millions of dollars invested in biotech. This issue was taken up only briefly during his confirmation hearing in December. Pointing to the revolving door at the FDA, Senator Sanders said, “At a time when the American people pay the highest prices in the world for prescription drugs and as drug companies continue to be the most powerful special interest in Washington, we need leadership at the FDA that is finally willing to stand up to the greed and power of the pharmaceutical industry.”
All of which suggests there’s not much chance that Califf would be the reformer the FDA needs. With eternal hope that the full Senate will reject him or, if he’s confirmed, he and the White House will pursue a reform agenda, we talked to several experts about their priorities for fixing the agency. In their view and ours, the following represent the top five actions that need to be taken.
1. Enforce commitments made by drugmakers.
The FDA awards expedited or fast-track approvals for drugs with a promise by the manufacturer that it will conduct further, more rigorous studies. However, by 2018, according to a recent review, companies followed through on only 38 percent (166 of 437) of drugs.
To ensure that studies get done, the agency must fully implement the National Academy of Medicine recommendations for a modern post-market tracking system. Such a database needs to log all studies of drugs on the market, published and unpublished, and all cases of harm, and it needs to be publicly available so outside researchers can keep watch on safety data and the FDA. The agency should also immediately withdraw drug approval when the manufacturer fails to conduct agreed-upon follow-up studies.
2. Rescind the approval of drugs that cause harm but don’t benefit patients.
When follow-up studies show that drugs are ineffective or dangerous, the FDA needs to pull them. Right now, drugs are still being prescribed to patients even though rigorous clinical trials have shown they don’t work. The agency recently allowed four out of six widely used (and heavily advertised) cancer drugs to stay on the market after their follow-up studies failed to show any benefit. Only five of 54 costly, toxic cancer drugs approved by the agency between 2008 and 2012 improved survival rates.
The FDA should immediately rescind approval for eteplirsen, the drug for Duchenne muscular dystrophy. Ditto the Alzheimer’s drug Aduhelm, which sets a precedent at the FDA for multiple similar medications that are waiting in the wings. Those should be forced to go through a thorough scientific vetting process rather than being approved on the same lousy reasoning that led to Aduhelm’s release.
3. Restore rigorous scientific standards.
Many experts, including multiple FDA insiders, have complained about the progressive decay of scientific standards at the agency. This has only gotten worse since 2016, with the passage of the 21st Century Cures Act, which gives the FDA enormous leeway in what kinds of studies it demands of companies in order to get their drugs approved. The FDA needs flexibility, says Steven Goodman, associate dean of clinical and translational research at Stanford, “but it has been erring on the side of lowering the scientific bar.”
For most drugs, companies should be required to produce two randomized clinical trials, the gold standard of medical science, showing that the drug provides meaningful benefit. Fewer drugs should be approved based on a “surrogate marker,” often an imaging study or blood test that is affected by a drug but may have little to do with whether or not patients benefit. “Too many FDA decisions have been based on wishful thinking rather than medical evidence,” says Diana Zuckerman, president of the National Center for Health Research, a Washington, D.C.–based public health think tank.
4. Clean house.
Somebody needs to jam the revolving door at the FDA. Physicians, scientists, and administrators come to the agency from industry, push industry-friendly decisions, and then leave government for new, lucrative positions in the private sector.
Take Patrizia Cavazzoni, the head of the FDA Center for Drug Evaluation and Research, who oversaw the approval of Aduhelm. Before joining the agency in 2019, Cavazzoni spent nearly two decades in high-level positions with the pharmaceutical giants Pfizer, Eli Lilly, and Sanofi-Aventis. After overruling the FDA advisory committee’s resounding vote against Aduhelm, she suggested that industry “partner” with the FDA in choosing committee members, an idea that violates the whole point of having outside, independent advisers.
Next up for the exits should be agency officials who seem to have forgotten who they serve. Billy Dunn, head of the Office of Neuroscience, met privately with Biogen officials after the FDA advisory committee’s no vote on Aduhelm. He then lobbied others at the agency to approve the drug, calling the ridiculously shaky scientific evidence presented by the company “extremely persuasive.”
Public Citizen, a nonprofit consumer advocacy group, has called for the removal of Cavazzoni and Dunn, along with FDA Acting Director Woodcock, who, despite having no financial ties to industry, has repeatedly supported agency decisions based on flimsy scientific evidence.
5. Stop Big Pharma financing.
Finally, President Biden should call on Congress to fully fund the FDA by repealing the legislation mandating that the drug industry pay for its own reviews. “What really needs to happen is to mitigate the power that Pharma already has over the FDA,” says Erick Turner, professor of psychiatry at Oregon Health & Science University and a former member of an FDA advisory committee. That can’t happen as long as the FDA is dependent on industry money.
Fully funding the FDA won’t be cheap. Still, other agencies that do a better job of regulating, like the Federal Aviation Administration and the Consumer Product Safety Commission, are supported by taxes. Surely the U.S., with the largest economy in the world, can afford the $2.5 billion annual cost of overseeing the approval of drugs without the help of industry largesse.
Criticism of the Food and Drug Administration
Numerous governmental and non-governmental organizations have criticized the U. S. Food and Drug Administration for alleged excessive and/or insufficient regulation. The U.S. Food and Drug Administration (FDA) is an agency of the United States Department of Health and Human Services and is responsible for the safety regulation of most types of foods, dietary supplements, drugs, vaccines, biological medical products, blood products, medical devices, radiation-emitting devices, veterinary products, and cosmetics. The FDA also enforces section 361 of the Public Health Service Act and the associated regulations, including sanitation requirements on interstate travel as well as specific rules for control of disease on products ranging from animals sold as pets to donations of human blood and tissue.
A $1.8 million 2006 Institute of Medicine report on pharmaceutical regulation in the U.S. found major deficiencies in the FDA system for ensuring the safety of drugs on the American market. Overall, the authors called for an increase in the regulatory powers, funding, and independence of the FDA.
Alleged problems in the drug approval process
The economist Milton Friedman has claimed that the regulatory process is inherently biased against approval of some worthy drugs, because the adverse effects of wrongfully banning a useful drug are undetectable, while the consequences of mistakenly approving a harmful drug are highly publicized and that therefore the FDA will take the action that will result in the least public condemnation of the FDA regardless of the health consequences.
Friedman and others have argued that delays in the approval process have cost lives. The thalidomide birth defects crisis led to passage of the 1962 Kefauver Harris Amendment, which required proof of efficacy in addition to safety for approval of new drugs — despite the fact that the thalidomide crisis was entirely a safety issue. Proving efficacy is much more expensive and time-consuming than proving safety. By requiring proof of efficacy in addition to safety, the Kefauver Harris Amendment added considerable cost and delay to the drug approval process — which critics say may well have cost many more lives than it was said to save. Prior to passage of the Kefauver Harris Amendment, the average time from the filing of an investigational new drug application (IND) to approval was 7 months. By 1998, it took an average of 7.3 years from the date of filing to approval. Prior to the 1990s, the mean time for new drug approvals was shorter in Europe than in the United States, although that difference has since disappeared.
Concerns about the length of the drug approval process were brought to the fore early in the AIDS epidemic. In the late 1980s, ACT-UP and other HIV activist organizations accused the FDA of unnecessarily delaying the approval of medications to fight HIV and opportunistic infections, and staged large protests, such as a confrontational October 11, 1988 action at the FDA campus which resulted in nearly 180 arrests. In August 1990, Louis Lasagna, then chairman of a presidential advisory panel on drug approval, estimated that thousands of lives were lost each year due to delays in approval and marketing of drugs for cancer and AIDS. Partly in response to these criticisms, the FDA introduced expedited approval of drugs for life-threatening diseases and expanded pre-approval access to drugs for patients with limited treatment options. All of the initial drugs approved for the treatment of HIV/AIDS were approved through accelerated approval mechanisms. For example, a “treatment IND” was issued for the first HIV drug, AZT, in 1985, and approval was granted 2 years later, in 1987. Three of the first 5 HIV medications were approved in the United States before they were approved in any other country.
Allegations that FDA regulation causes higher drug prices
Studies published in 2003 by Joseph DiMasi and colleagues estimated an average cost of approximately $800 million to bring a new drug to market, while a 2006 study estimated the cost to be anywhere from $500 million to $2 billion. The consumer advocacy group Public Citizen, using a different methodology, estimated the average cost for development to be under $200 million, about 29% of which is spent on FDA-required clinical trials. DiMasi rejects the claim that high R&D costs alone are responsible for high drug prices. Instead, in a published letter, DiMasi writes, “…longer development times increase R&D costs and shorten the period during which drug companies can earn the returns they need to make investment financially viable. Other things being equal, longer development times reduce innovation incentives. As a consequence, fewer new therapies might be developed.”
Economist Gary S. Becker, who won the Nobel Memorial Prize in Economics, has argued that FDA-required clinical trials for new drugs do contribute to high drug prices for consumers, mainly because of patent protection that provides a temporary monopoly which disallows cheaper alternatives from entering the market. He advocates dropping many FDA requirements, many of which provide no additional safety or valuable information, as this would hasten the development of new drugs, because they would be faster to bring to market, thereby increasing supply, and as a consequence would lead to lower prices.
Charges of under-regulation
In addition to those who see the FDA as a source of excessive regulation, other critics believe that the FDA does not regulate some products strictly enough. According to this view, the FDA allows unsafe drugs on the market because of pressure from pharmaceutical companies, fails to ensure safety in drug storage and labeling, and allows the use of dangerous agricultural chemicals, food additives, and food processing techniques.
A $1.8 million 2006 Institute of Medicine report on pharmaceutical regulation in the U.S. found major deficiencies in the current FDA system for ensuring the safety of drugs on the American market. Overall, the authors called for an increase in the regulatory powers, funding, and independence of the FDA.
Allegations that the FDA covered up exportation of unsafe products
In the 1980s, Cutter Laboratories introduced a heat-treated version of Factor VIII concentrate in the US, designed to eliminate the risk of HIV transmission. However, Cutter continued to market the untreated product overseas, potentially spreading HIV while the safer product was marketed in the US.
Cutter initially had a voluntary agreement with the FDA to stop marketing the untreated product. However, when it became clear that Cutter was not complying with the agreement, the FDA ordered the company to cease marketing untreated blood products, stating: “It was unacceptable for them to ship that material overseas.” At the same time, the FDA, according to Cutter’s internal documents, asked that the issue be “quietly solved without alerting the Congress, the medical community and the public”, leading to charges that the FDA was complicit in covering up Cutter’s actions.
Allegations that unsafe drugs are approved
Some critics believe that the FDA has been apt to overlook safety concerns in approving new drugs, and is slow to withdraw approved drugs once evidence shows them to be unsafe. Rezulin (troglitazone) and Vioxx (rofecoxib) are high-profile examples of drugs approved by the FDA which were later withdrawn from the market for posing unacceptable risks to patients.
Troglitazone is a diabetes drug that was also available abroad at the time the FDA approved it. Post-marketing safety data indicated that the drug had dangerous side-effects (in this case liver failure). The drug was pulled off that market in the UK in 1997, but was not withdrawn by the FDA until 2000, before which time it is claimed that thousands of Americans were injured or killed by the drug.
In the case of Vioxx, a pre-approval study indicated that a group taking the drug had four times the risk of heart attacks when compared to another group of patients taking another anti-inflammatory, naproxen. The FDA approval board accepted the manufacturer’s argument that this was due to a previously unknown cardioprotective effect of naproxen, rather than a risk of Vioxx, and the drug was approved. In 2005, the results of a randomized, placebo-controlled study showed that Vioxx users suffered a higher rate of heart attacks and other cardiovascular disorders than patients taking no medication at all. The manufacturer, Merck, withdrew the drug after disclosures that it had withheld information about its risks from doctors and patients for over five years, resulting in between 88,000 and 140,000 cases of serious heart disease of which roughly half died. David Graham, a scientist in the Office of Drug Safety within the CDER, testified to Congress that he was pressured by his supervisors not to warn the public about dangers of drugs like Vioxx. He argued that an inherent conflict of interest exists when the office responsible for post-approval monitoring of drug safety is controlled by the same organization which initially approved those same drugs as safe and effective. He said that after testifying against Vioxx, he was “marginalized by FDA management and not asked to participate in the evaluation of any new drug safety issues. It’s a type of ostracism.” In a 2006 survey sponsored by the Union of Concerned Scientists, almost one-fifth of FDA scientists said they “have been asked, for non-scientific reasons, to inappropriately exclude or alter technical information or their conclusions in an FDA scientific document.”
Allegations that unsafe food additives and processing technologies are approved
Food safety advocates have criticized the FDA for allowing meat manufacturers to use carbon monoxide gas mixtures during the packaging process to prevent discoloration of meat, a process that may hide signs of spoilage from the consumer.
The FDA has been criticized for allowing the use of recombinant bovine growth hormone (rBGH) in dairy cows. rBGH-treated cows secrete higher levels of insulin-like growth factor 1 (IGF-1) in their milk than do untreated cows. IGF-1 signaling is thought to play a role in sustaining the growth of some tumors, although there is little or no evidence that exogenously absorbed IGF could promote tumor growth. The FDA approved rBGH for use in dairy cows in 1993, after concluding that humans drinking such milk were unlikely to absorb biologically significant quantities of bovine IGF-1. A 1999 report of the European Commission Scientific Committee on Veterinary Measures relating to Public Health noted that scientific questions persist regarding the theoretical health risks of milk from rBGH-treated cows, particularly for feeding to infants. Since 1993, all EU countries have maintained a ban on rBGH use in dairy cattle.
The FDA has also been criticized for permitting the routine use of antibiotics in healthy domestic animals to promote their growth, a practice which allegedly contributes to the evolution of antibiotic-resistant strains of bacteria. The FDA has taken recent steps to limit the use of antibiotics in farm animals. In September 2005, the FDA withdrew approval for the use of the fluoroquinolone antibiotic enrofloxacin (trade name Baytril) in poultry, out of concern that this practice could promote bacterial resistance to important human antibiotics such as ciprofloxacin.
The FDA has received criticism for its approval of certain coal tar derived food dyes such as FDC yellow 5 and 6, which are banned in most European countries. On September 6, 2007, the British Food Standards Agency revised advice on certain artificial food additives, including tartrazine.
Professor Jim Stevenson from Southampton University and author of the report said: “This has been a major study investigating an important area of research. The results suggest that consumption of certain mixtures of artificial food colors and sodium benzoate preservative are associated with increases in hyperactive behavior in children.
The following additives were tested in the research:
- Sunset yellow (FD&C Yellow #6) – Reddish-yellow coloring used in many foods and cosmetics
- Carmoisine – Red coloring used in jellies
- Tartrazine (FD&C Yellow #5) – Yellow coloring
- Ponceau 4R – Red coloring
- Sodium benzoate – Preservative
- Quinoline yellow – Food coloring
- Allura red AC (FD&C Red #40) – Orange / red food dye
On April 10, 2008, the Food Standards Agency called for a voluntary removal of the colors (but not sodium benzoate) by 2009. In addition, it recommended that there should be action to phase them out in food and drink in the European Union (EU) over a specified period.
UK ministers have agreed that the six colorings will be phased out by 2009. A Japanese group found in 1987 that tartrazine was not carcinogenic after being fed to mice for two years. A German group found in 1989 that Sunset Yellow did not induce mutations that could lead to cancer in laboratory animals.
The FDA has also been criticized for giving permission for cloned animals to be sold as food without any special labeling, although “cloned products may not reach the U.S. market for years.” and “Authorities lack the authority to require labeling of products from cloned animals.”
In August 2013, a study released by The Pew Charitable Trusts found that of the 8105 additives that the FDA allows in food only 19% (1367) have toxicology information.
Charges of FDA bias
Allegations of undue pharmaceutical industry influence
Pressure to allow pharmaceuticals
After his resignation, from his post as Commissioner of the Food and Drugs Administration in December 1969, Dr. Herbert L. Ley, Jr. In an interview to The New York Times, warned the public about the FDA’s inability to safeguard consumers. People were being misled, he believed “The thing that bugs me is that the people think the FDA is protecting them – it isn’t. What the FDA is doing and what the public thinks it’s doing are as different as night and day,” he said. The agency, in his opinion, did not have the motivation to protect consumers, faced budget shortfalls, and lacked support from the Department of Health, Education, and Welfare. Dr. Ley was critical of Congress, the Administration and the drug industry, stating that he had “constant, tremendous, sometimes unmerciful pressure” from the drug industry, and that the drug company lobbyists, combined with the politicians who worked on behalf of their patrons, could bring “tremendous pressure” to bear on him and his staff, to try preventing FDA restrictions on their drugs. Ley stated that the entire issue was about money, “pure and simple”. On December 15, 1999, interviewed for the oral history program of the FDA History Office, Dr. Ley shared that from the first controversy in his tenure as FDA Commissioner he had a “gut feeling” that his life expectancy at the FDA was probably limited. He said he had done everything by the book, both in the FDA and the Department of Health, Education, and Welfare, and he thinks that what the Administration was really wishing, was that he would stonewall the whole Academy report because it was goring too many pharmaceutical companies.
Viewing the pharmaceutical industry as FDA clients
In a 2005 interview, Dr. David Graham, associate director of the FDA’s Office of Drug Safety, stated that “FDA is inherently biased in favor of the pharmaceutical industry. It views industry as its client, whose interests it must represent and advance. It views its primary mission as approving as many drugs it can, regardless of whether the drugs are safe or needed”
The Prescription Drug User Fee Act allows the FDA to augment its budget by charging fees to pharmaceutical firms. Over $800 million was collected from 1993 to 2001 and rising each year. It also has been shown that oftentimes, the FDA expert advisory panels had direct financial interests in the drugs or products being evaluated. Former Editor of The New England Journal of Medicine, Marcia Angell, has stated that “It’s time to take the Food and Drug Administration back from the drug companies…. In effect, the user fee act put the FDA on the payroll of the industry it regulates. Last year, the fees came to about $300 million, which the companies recoup many times over by getting their drugs to market faster.” Critics have disputed the claim that the Prescription Drug User Fee Amendment has improved the speed of drug approvals.
On April 14, 2017, House and Senate leaders announced a bipartisan agreement to extend the FDA’s ability to collect high user fees from drug companies and medical device manufacturers. This allows the FDA to charge huge licensing fees to drug manufacturers, which has led to enormous increases in generic drug pricing. In 2013 and 2014, generic drug pricing for over 200 drugs increased over 100%. Many of those drugs had price hikes over 1000%. It has been reported that 75% of the FDA generic drug oversight budget comes directly from private drug companies.
Bias toward more expensive drug
A historical example of how the FDA seemingly favors the pharmaceutical industry either from clandestine direct money payments to FDA directors and scientific advisers or other undisclosed or unknown means was seen with the generic drug droperidol. Droperidol was a widely used antiemetic used perioperatively safely for over 30 years. During that time there had never been a case reported in peer-reviewed medical literature of cardiac arrhythmias or cardiac issues when given at doses typically used for post-operative nausea and vomiting. Nonetheless, and without warning, in 2001 the FDA issued a black box warning regarding QTc prolongation (a dangerous finding on an ECG which can lead to cardiac arrest) with the use of droperidol. This effectively killed the common use of droperidol and made way for heavy usage of the much more expensive non-generic 5-HT3 serotonin receptor antagonists on the market even though these newer drugs had also been shown to prolong QTc as much, if not more than droperidol. In addition, each of the 5-HT3 antagonists available at that time had peer-reviewed reports of causing significant cardiac abnormalities, and in some cases, death. Despite an apparent discrepancy that deeply concerned the anesthesia and emergency room physician community, the FDA persisted in keeping the black box warning, while at the same time did not place any restrictions on the more expensive 5-HT3 antagonists.
Allegations of bias against gay men in blood donation process
Blood collecting organizations, such as the American Red Cross, have policies in accordance with FDA guidelines that prohibit accepting blood donations from any “male who has had sex with another male since 1977, even once”. The inclusion of homo- and bisexual men on the prohibited list has created some controversy, but the FDA and Red Cross cite the need to protect blood recipients from HIV as justification for the continued ban. Even with PCR-based testing of blood products, a “window period” may still exist in which an HIV-positive unit of blood would test negative. All potential donors from HIV high-risk groups are deferred for this reason, including men who have sex with men. The issue has been periodically revisited by the Blood Products Advisory Committee within the FDA Center for Biologics Evaluation and Research and was last reconfirmed on May 24, 2007. Documentation from these meetings is available to the public.
However, in 2006, the AABB, America’s Blood Centers and American Red Cross recommended to the FDA that the deferral period for men who had sex with other men should be changed to be equivalent with the deferral period for heterosexual’s judged to be at risk. The FDA chose to uphold the blood ban. Female sexual partners of MSM (men who have sex with men) are deferred for one year since the last exposure. This is the same policy used for any sexual partner of someone in a high-risk group. The intent of these policies is to ensure that blood is collected from a population that is at low risk for disease, since the tests are not perfect and human error may lead to infected units not being properly discarded. The policy was first put in place in 1985.
Criticism of FDA’s rejection of medical cannabis
In April 2005, the FDA issued a statement asserting that cannabis had no medical value and should not be accepted as a medicine, despite a great deal of research suggesting the opposite. The supporters of medical cannabis legalization criticized the FDA’s statement as a politically motivated one instead of one based on solid science. A group of congressmen led by Maurice Hinchey wrote a letter to FDA’s commissioner Andrew von Eschenbach, expressing their disapproval of the FDA’s statement and pointed out the FDA’s rejection of medical cannabis was inconsistent with the findings of the Institute of Medicine, which stated cannabis does have medical benefits. While the FDA has not approved marijuana it has approved THC (a compound found in cannabis) as an active ingredient for medicinal use. Critics argue that this approval is a politically motivated attempt to allow special interest groups to have patents over the substance, perhaps because the patents on previously patented competing substances have expired.
Allegations regarding management and FDA scientists
Nine FDA scientists appealed to President George W. Bush and at the time, President-elect Barack Obama over pressure from management to manipulate data, mainly in relation to the review process for medical devices. These concerns were highlighted in a 2006 report on the agency as well.
Risky Drugs: Why The FDA Cannot Be Trusted
A forthcoming article for the special issue of the Journal of Law, Medicine and Ethics (JLME), edited by Marc Rodwin and supported by the Edmond J. Safra Center for Ethics, presents evidence that about 90 percent of all new drugs approved by the FDA over the past 30 years are little or no more effective for patients than existing drugs.
All of them may be better than indirect measures or placebos, but most are no better for patients than previous drugs approved as better against these measures. The few superior drugs make important contributions to the growing medicine chest of effective drugs.
The bar for “safe” is equally low, and over the past 30 years, approved drugs have caused an epidemic of harmful side effects, even when properly prescribed. Every week, about 53,000 excess hospitalizations and about 2400 excess deaths occur in the United States among people taking properly prescribed drugs to be healthier. One in every five drugs approved ends up causing serious harm, while one in ten provide substantial benefit compared to existing, established drugs. This is the opposite of what people want or expect from the FDA.
Prescription drugs are the 4th leading cause of death. Deaths and hospitalizations from over-dosing, errors, or recreational drug use would increase this total. American patients also suffer from about 80 million mild side effects a year, such as aches and pains, digestive discomforts, sleepiness or mild dizziness.
The forthcoming article in JLME also presents systematic, quantitative evidence that since the industry started making large contributions to the FDA for reviewing its drugs, as it makes large contributions to Congressmen who have promoted this substitution for publicly funded regulation, the FDA has sped up the review process with the result that drugs approved are significantly more likely to cause serious harm, hospitalizations, and deaths. New FDA policies are likely to increase the epidemic of harms. This will increase costs for insurers but increase revenues for providers.
This evidence indicates why we can no longer trust the FDA to carry out its historic mission to protect the public from harmful and ineffective drugs. Strong public demand that government “do something” about periodic drug disasters has played a central role in developing the FDA. Yet close, constant contact by companies with FDA staff and officials has contributed to vague, minimal criteria of what “safe” and “effective” mean. The FDA routinely approves scores of new minor variations each year, with minimal evidence about risks of harm. Then very effective mass marketing takes over, and the FDA devotes only a small percent of its budget to protect physicians or patients from receiving biased or untruthful information. The further corruption of medical knowledge through company-funded teams that craft the published literature to overstate benefits and understate harms, unmonitored by the FDA, leaves good physicians with corrupted knowledge. Patients are the innocent victims.
Although it now embraces the industry rhetoric about “breakthrough” and “life-saving” innovation, the FDA in effect serves as the re-generator of patent-protected high prices for minor drugs in each disease group, as their therapeutic equivalents lose patent protection. The billions spent on promoting them results in the Inverse Benefit Law: the more widely most drugs are marketed, the more diluted become their benefits but more widespread become their risks of harm.
The FDA also legitimates industry efforts to lower and widen criteria prescribing drugs, known by critics as “the selling of sickness.” Regulations conveniently prohibit the FDA from comparing the effectiveness of new drugs or from assessing their cost-effectiveness. Only the United States allows companies to charge what they like and raise prices annually on last year’s drugs, without regard to their added value.
A New Era?
Now the FDA is going even further. The New England Journal of Medicine has published, without comment, proposals by two senior figures from the FDA to loosen criteria drugs that allege to prevent Alzheimer’s disease by treating it at an early stage. The authors seem unaware of how their views about Alzheimer’s and the role of the FDA incorporate the language and rationale of marketing executives for the industry. First, they use the word “disease” to refer to a hypothetical “early-stage Alzheimer’s disease” that supposedly exists “before the earliest symptoms of Alzheimer’s disease are apparent.” Notice that phrasing assumes that the earliest symptoms will become apparent, when in fact it’s only a hypothetical model for claiming that cognitive lapses like not remembering where you put something or what you were going to say are signs of incipient Altzheimer’s disease. The proposed looser criteria would legitimate drugs as “safe and effective” that have little or no evidence of being effective and expose millions to risks of harmful side effects.
No proven biomarkers or clinical symptoms exist, the FDA officials note, but nevertheless they advocate accelerated approval to allow “drugs that address an unmet medical need.” What “unmet need”? None exists. This market-making language by officials who are charged with protecting the public from unsafe drugs moves us towards the 19-century hucksterism of peddling cures of questionable benefits and hidden risks of harm, only now fully certified by the modern FDA.
The main reason for advocating approvals of drugs for an unproven need with unproven benefits, these FDA officials explain, is that companies cannot find effective drugs for overt Alzheimer’s. Their drug-candidates have failed again and again in trials. The core rationale of the proposed loosening of criteria is that “the focus of drug development has sifted to earlier stages of Alzheimer’s disease…and the regulatory framework under which such therapies are evaluated should evolve accordingly.” Yet they admit there are no “therapies” in this much larger market where (with the help of the industry-funded FDA) companies will not have to prove their drugs are effective. In fact, these FDA officers propose to approve the drugs without ever knowing if they are therapeutic or not. Their commercialized language presumes the outcome before starting. The job of the FDA, it seems, is to help drug companies open up new markets to increase profits for the FDA’s corporate paymasters.
These two FDA officials maintain that “the range of focus must extend to healthy people who are merely at risk for the disease but could benefit from preventive therapies.” Yet they admit we do not know who is “at risk,” nor whether there is a “disease,” nor whether anyone “could benefit,” nor whether the drugs constitute “preventive therapies.” Similar FDA-encouraged shifts have been made for drugs treating pre-diabetes, pre-psychosis, and pre-bone density loss, with few or no benefits to offset risks of harm. This week, based on policy research at the Edmond J. Safra Center for Ethics, a letter of concern was published in the New England Journal of Medicine. The authors write that approval for drugs to treat “early stage Altzheimer’s disease” must meet “a much higher bar – evidence of slowed disease progression.” But without clinical manifestations or biomarkers for an alleged disease, how will such progression be measured?
The F.D.A. Is in Trouble. Here’s How to Fix It.
Some New Year’s resolutions for the incoming boss.
The Food and Drug Administration is in distress. The agency is still the world’s leading regulator of food and medical products, responsible for ensuring the safety of some $2.6 trillion in consumer goods each year. That represents 20 cents of every dollar that Americans spend. But critics both inside and outside the sprawling agency say that the F.D.A.’s standards have been slipping for some time.
The effects of that slippage are starting to show. Too many prescription drugs and medical devices are being approved with too little data on how safe or effective they are. And too many other products — like those containing CBD or THC, ingredients found in the marijuana plant — are being sold with no apparent oversight at all.
Part of the problem is that the agency has too few resources and too little power to fulfill its key responsibilities. But it has also become profoundly vulnerable to political interference and other special interests. And a revolving door — F.D.A. staffers frequently go on to lucrative jobs at the very companies they were tasked with policing — has hurt the agency’s credibility.
So too have a string of high-profile public health crises. In just the past few years, the F.D.A. has been faulted for its roles in the opioid epidemic (regulators allowed too many opioids on the market without properly flagging them as addictive or deadly) and a surge in youth vaping (the agency failed to keep untested e-cigarettes off the market or to establish the safety of these products, as millions began using them).
Given all that, it’s worrisome that the F.D.A. spent most of 2019 without a permanent commissioner. It’s also concerning that the person finally picked to fill the post — Dr. Stephen Hahn, an oncologist and researcher who was sworn in last month — has no significant policy experience nor any real record of his views on the agency he’s now in charge of. Dr. Hahn’s predecessor, Dr. Scott Gottlieb, came to the F.D.A. with reams of both, and, despite a mere two-year tenure, received bipartisan praise for his efforts to balance the demands of public health under significant public, political and financial pressures.
Dr. Hahn did spend two years as chief medical officer of M.D. Anderson Cancer Center in Houston, where, according to his supporters, he helped the institution recover from several ethical and financial crises. But the scope of that work was vastly different from what awaits Dr. Hahn at the F.D.A. And he assumes this new role at a particularly tumultuous moment. His boss’s boss, President Trump, was just impeached; a presidential election is underway; and the agency is facing pressure from companies, politicians and patients to loosen its standards and clear more products for market faster.
Some of that pressure to speed things up is understandable, especially from patients who are frustrated by a lack of treatment options. But several entities — including drug and device companies seeking easier profits and libertarian groups bent on deregulation at any cost — are exploiting those frustrations in an attempt to substantially curtail the F.D.A.’s already diminished powers.
There is a deep tension between groups that want medical products to be proved safe and effective before they are made widely available and those that say that as long as those products pass a bare minimum of safety testing, patients should be able to decide for themselves. “The F.D.A. has been moving in the latter direction under great political and public pressure,” says Dr. Steven Joffe, a bioethicist at the University of Pennsylvania. If that trend continues, the nation may end up with a regulatory agency that’s powerless to make any meaningful regulations.
For all its faults and failures, the F.D.A. has traditionally done a great deal to balance access to innovations with protection from danger or fraud. To maintain that balance, the agency needs to be made stronger, not weaker.
Fortunately, options for fortifying the F.D.A. abound. For instance, laws that would make it easier for regulators to police the cosmetics industry and to hold medical device companies to account have been floating through Congress for years. A group of former F.D.A. commissioners last year proposed an even bolder fix: Restore the agency’s autonomy by extracting it from the Department of Health and Human Services. The F.D.A.’s decisions used to be final, but for decades now they have been subject to layers of political interference. Making the agency independent, as the Federal Reserve and the Social Security Administration are, could help reverse that trend.
But for these or other worthy ideas to get a fair hearing, Congress will have to step in, and the president — and the electorate — will need to come to terms with the essential role of regulations in protecting the nation’s food and drug supply.
In the meantime, the challenge of steering the F.D.A. will fall to Dr. Hahn. He will not have nearly enough resources to carry out the agency’s stated mission — no commissioner ever does. But he will not be completely powerless, either. Here are four things Dr. Hahn would do well to keep in mind as he takes the reins.
Stay vocal. Dr. Hahn’s predecessor, Dr. Gottlieb, managed to keep a spotlight on his chosen priorities — namely e-cigarette regulations and generic drug development — with a relentless and multifaceted public messaging campaign. He tweeted, he blogged, he gave speeches and he communicated openly and regularly with the press. Dr. Gottlieb did not achieve all of his goals — in fact his e-cigarette strategy backfired, badly. But he made the F.D.A. less opaque, and he gave the agency an urgently needed voice. Dr. Hahn will have an easier time defending the agency, and keeping it relevant, if he fosters the same transparency.
Slow down on drug and device approvals. The F.D.A. has made several compromises in recent years — such as accepting “real world” or “surrogate” evidence in lieu of traditional clinical trial data — that have enabled increasingly dubious medical products to seep into the marketplace. Dr. Hahn ought to take a fresh look at some of these shifting standards and commit to abandoning the ones that don’t work. That will almost certainly mean that the approval process slows down — and that’s O.K.
Stand up for science. As reporting from the medical news website Stat and other outlets suggests, the F.D.A. has become too susceptible to outside pressure. Regulators approved a powerful new opioid at the Department of Defense’s urging, fast-tracked a dubious antidepressant after President Trump praised it, and reversed its decision to reject a muscular dystrophy drug after patient groups complained loudly. Such kowtowing hardly inspires confidence. Scientific evidence (or the lack thereof) needs to be the deciding factor in any final regulations from the F.D.A. That means saying no to politicians and drug and device makers — as well as patients’ groups — when their demands are not supported by the agency’s own findings. It also means holding companies to account when they fail to complete post market studies, or when their products prove faulty or dangerous.
Follow through on existing commitments. The F.D.A. has yet to issue guidelines for the regulation of increasingly popular CBD products after promising to do so by the end of 2019. E-cigarette makers are supposed to submit their applications for market approval to the agency by May. And a regulatory grace period that the agency granted to so-called stem cell clinics back in 2017 is set to expire this year; when it does, regulators will need to figure out how to police nearly 1,000 businesses selling injections and other treatments that have not proved to work and that have already caused some patients serious harm. Dr. Hahn would build a lot of good will if he showed the F.D.A.’s critics — and the public at large — that he takes all of these deadlines seriously.
The Deadly Incompetence of the FDA
And I’ve explained why private regulation actually is a very effective way of promoting health and safety.
Today, let’s get specific and look at the Food and Drug Administration. This bureaucracy ostensibly is supposed to protect us by making sure drugs and medical devices are safe and effective before getting approval, which seems like it might be a reasonable role for government.
…the FDA has an incentive to delay the introduction of new drugs because approving a bad drug (Type I error) has more severe consequences for the FDA than does failing to approve a good drug (Type II error). In the former case at least some victims are identifiable and the New York Times writes stories about them and how they died because the FDA failed. In the latter case, when the FDA fails to approve a good drug, people die but the bodies are buried in an invisible graveyard.
This video from Learn Liberty looks at some data on how the FDA’s Type II errors have led to thousands of deaths, but mostly focuses on whether people and medical professionals should have the freedom to makes choices different from what the FDA has officially blessed.
It’s also worth mentioning that the process of drug approval is jaw-droppingly expensive, as Professor Tabarrok noted in another column.
It costs well over a billion dollars to get the average new drug approved and much of that cost comes from FDA required clinical trials. Longer and larger clinical trials mean that the drugs that are eventually approved are safer. But longer trials also mean that good drugs are delayed. And the more expensive it is to produce new drugs the fewer new drugs will be produced. In short, longer and larger trials mean drug delay and drug loss.
The FDA bureaucracy can’t even approve things it already has approved. There was a big controversy a few months ago about the EpiPen, which is a very expensive device that auto-injects medication to people suffering severe allergic reactions.
But the device is only costly because the FDA is hindering competition, as noted by the Wall Street Journal.
Epinephrine is a basic and super-cheap medicine, and the EpiPen auto-injector device has been around since the 1970s. Thus EpiPen should be open to generic competition, which cuts prices dramatically for most other old medicines. Competitors have been trying for years to challenge Mylan’s EpiPen franchise with low-cost alternatives—only to become entangled in the Food and Drug Administration’s regulatory afflatus. …the FDA maintains no clear and consistent principles for generic drug-delivery devices like auto injectors or asthma inhalers. …injecting a kid in anaphylactic shock with epinephrine…is not complex medical engineering. But no company has been able to do so to the FDA’s satisfaction.
Research from the Mercatus Center reveals that the FDA imposes ever-higher costs and gets ever-higher budgets, but also how the bureaucracy fails to deliver on its obligation to facilitate innovation.
The expense of putting drugs and devices through this system is almost unimaginable. The cost of bringing low- to medium-risk 510(k) medical devices to market averages $31 million, $24 million (75 percent) of which is dedicated solely to attaining FDA approval within an average of about six months. Any significant improvement to the device requires reapplication. For higher-risk medical devices where there may be significant health gains, the costs are about $94 million, $75 million (80 percent) of which is dedicated to attaining FDA approval. For drugs, the situation is much worse. It costs an average of $2.6 billion simply to get a drug through the FDA process and onto the market. This does not include postmarket monitoring, the terms of which are laid out by FDA upon approval. These costs have increased from about $1 billion between 1983 and 1994. …we continue to increase the funding and authority for FDA and assume that we will somehow boost innovation in medical products (drugs and devices) despite the growing obstacles. This has not happened. …Congress continues to increase funding for FDA through both the general fund and industry user fees…with the hope that performance goals and additional funding would increase FDA’s performance and lead to an increase in innovations. …but FDA finds strategic ways to narrowly meet each goal while frustrating the original goal of improving health outcomes through innovation.
By the way, the FDA also does really bone-headed things. I’ve previously written about the bureaucracy’s war against unpasteurized milk (including military-style raids on dairies!). Now the bureaucrats think soldiers shouldn’t be allowed to get cigars.
The Wall Street Journal has the details of this silly nanny-state intervention.
You might think GIs in Iraq and Afghanistan have enough to worry about with Islamic State and the Taliban. But it turns out they’ve also got a problem called the Food and Drug Administration. In August a new FDA rule went into effect that forbids tobacco makers and distributors from handing out free samples. Some companies that have been donating cigars to service members for decades have now stopped for fear that this is now illegal. The FDA nuttiness has attracted the attention of Rep. Kathy Castor, a Democrat who represents Florida’s 14th district, which includes “Cigar City,” or Tampa. She has introduced a bill to “reinstate the tradition of donating cigars to our military members to provide them with a taste of home while deployed.” Her press release notes that cigars are the “second-most requested item” from troops overseas. …cigars for service members is in question because it’s a proxy for the political war on tobacco, but the first casualty is common sense. The FDA’s bureaucrats are happy to have U.S. soldiers, sailors, airmen and Marines dodge bullets overseas but they’re horrified they might relax by lighting up a stogie.
But the nanny-state war against soldiers enjoying cigars is downright trivial compared to the deadly impact of the FDA’s attack on vaping.
Jacob Sullum of Reason outlines some of the horrifying details.
The Food and Drug Administration’s e-cigarette regulations, which took effect last week, immediately struck two blows against public health. As of Monday, companies that sell vaping equipment and the fluids that fill them are forbidden to share potentially lifesaving information about those products with their customers. They are also forbidden to make their products safer, more convenient, or more pleasant to use. The FDA’s censorship and its ban on innovation will discourage smokers from switching to vaping, even though that switch would dramatically reduce the health risks they face. That effect will be compounded by the FDA’s requirement that manufacturers obtain its approval for any vaping products they want to keep on the market for longer than two years. The cost of meeting that requirement will force many companies out of business… All of this is unambiguously bad for consumers and bad for public health. Yet the FDA took none of it into account…the Family Smoking Prevention and Tobacco Control Act…gave the FDA authority over tobacco products, a category to which it has arbitrarily assigned tobacco-free e-cigarettes, even when they contain nicotine that is not derived from tobacco or no nicotine at all. …A brief that 16 advocates of tobacco harm reduction filed last week in support of Nicopure’s lawsuit notes that the cost of the FDA’s regulations will far outweigh their benefit if they cause even a small percentage of vapers to start smoking again or deter even a small percentage of current smokers from switching. That’s because of the huge difference in risk between e-cigarettes and the conventional kind (at least 95 percent, according to the Royal College of Physicians)… The FDA acknowledges that its regulations might also harm public health by retarding the substitution of vaping for smoking. But it does not include that cost in its analysis, deeming it too speculative. The FDA literally assigns zero value to the lives of smokers who would have quit were it not for the agency’s heavy-handed meddling.
Oh, I suppose I also should mention that FDA red tape is responsible for the fact that Americans have a much more limited selection of condoms than Europeans.
I’m sure there’s a good joke to be made about the bureaucrats screwing us in ways that interfere with us…um…well, you know.
Let’s wrap up with some tiny bits of good news. First, Arizona’s Goldwater Institute has been remarkably successful in getting states to adopt “Right to Try” laws that give seriously ill people the right to try investigational medications.
Sadly, those laws will have limited use until there’s also reform in Washington. Fortunately, there’s some movement. Here’s a video from a congressional hearing organized by Senator Johnson of Wisconsin.
Here’s a second item that sort of counts as good news.
If there is one silver lining to the dark cloud of FDA incompetence, it’s that the bureaucrats haven’t figured out how to criminalize those who use drugs for “off-label” purposes (i.e., for reasons other than what was approved by the government). A good example, as reported by the New York Times, is a tooth desnsitizer that’s only been recently approved by the FDA (after being available for decades in nations such as Japan), and already dentists are using it to fight cavities.
Nobody looks forward to having a cavity drilled and filled by a dentist. Now there’s an alternative: an antimicrobial liquid that can be brushed on cavities to stop tooth decay — painlessly. The liquid is called silver diamine fluoride, or S.D.F. It’s been used for decades in Japan, but it’s been available in the United States, under the brand name Advantage Arrest, for just about a year. The Food and Drug Administration cleared silver diamine fluoride for use as a tooth desensitizer for adults 21 and older. But studies show it can halt the progression of cavities and prevent them, and dentists are increasingly using it off-label for those purposes. …Silver diamine fluoride is already used in hundreds of dental offices. Medicaid patients in Oregon are receiving the treatment…it’s relatively inexpensive. …The noninvasive treatment may be ideal for the indigent, nursing home residents and others who have trouble finding care. …But the liquid may be especially useful for children. Nearly a quarter of 2- to 5-year-olds have cavities
Since I’m not familiar with the history of the FDA, I wonder whether the bureaucrats have ever tried to block medical professionals from using drugs and devices for “off-label” purposes.
Let me close with one final point. Our leftist friends aren’t very interested in reforming the FDA.
Instead, they argue that the big problem is greedy pharmaceutical companies and suggest European-style price controls.
That could save consumers money in the short run, I’m sure, but it would gut the incentive to develop new medications.
One expert looked at the Rand Corporation estimates that such policies would lead to a decline in life expectancy of 0.7 years by 2016. He then crunched the numbers and concluded that the aggregate impact would be worst thing to ever happen. Even worse than the brutality of Mao’s China.
…let me put this in context. In 2060 there will probably be 420 million Americans and 523 million Europeans. And suppose that whatever changes we make in drug regulations today last for one human lifespan, so that everybody has a chance to be 55-60. So about a billion people each losing about 0.7 years of their life equals 700 million life-years. Since some people live in countries outside the US and Europe  and they also benefit from First-World-invented medications, let’s round this up to about a billion life-years lost. What was the worst thing that ever happened? One strong contender is Mao’s Great Leap Forward, in which ineffective agricultural reforms and very effective purges killed 45 million people. Most of these people were probably already adults, and lifespan in Mao’s China wasn’t too high, so let’s say that each death from the Great Leap Forward cost what would otherwise be twenty healthy life years. In that case, the worst thing that has ever happened until now cost 45 million 20 = 900 million life-years. Once again, RAND’s calculations plus my own Fermi estimate suggest that prescription drug price regulation would cost one billion life-years, which would very slightly edge out Communist China for the title of Worst Thing Ever.
I guess the bottom line is that the FDA is a typical regulatory agency, both incompetent and expensive. But if the statists have their way, things could get a lot worse.
drugwatch.com, “Misplaced Trust: Why FDA Approval Doesn’t Guarantee Drug Safety.” By Michelle Llamas; center4research.org, “What’s Wrong with the FDA?” By Shannon Brownlee and Jeanne Lenzer; en.wikipedia.org, “Criticism of the Food and Drug Administration.” By Wikipedia Editors; ethicsharvard.edu, “Risky Drugs: Why The FDA Cannot Be Trusted.” By Donald W. Light; nytimes.com, “The F.D.A. Is in Trouble. Here’s How to Fix It. Some New Year’s resolutions for the incoming boss.” By the editorial board; fee.org, “The Deadly Incompetence of the FDA: The FDA routinely does really foolish things that undermine public health.” By Daniel J. Mitchell;
How We Sold Our Soul Postings