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Criticism of the FDA Author: User:Regulations The United States Food and Drug Administration has regulatory oversight over a large array of products that effect the health and life of American citizens As a result, the FDA's powers and decisions are carfully monitored by several governmental and non-governmental organizations. There are manys criticisms and complaints lodged against the FDA from patients, economists, regulatory bodies, and the pharmaceutical industry.

Over-regulation
There are trade-offs in regard to regulation. Increase the safety standards keeps some drugs from coming to market as well as increases the time it takes for drugs to come to market, therefore there is some suffering and deaths during that time that could have been averted if the standard were more relaxed. However, decreasing the safety standards allows dangerous drugs to come to market that would otherwise not have, therefore also causing some suffering and deaths. Increasing standards also makes it more costly to bring drugs to market, which prevent some drugs from coming to market at all. In trying to prevent bad drugs from coming to market, good drugs are slowed or prevented from coming to market. The question is at what level to set the standards so that more suffering is alleviated than caused, or whether to eliminate government from setting the standards at all and leaving it to the market with voluntary approvals either by the FDA or private certifiers. According to economist Daniel B. Kline who researched economists' views, "many economists" would agree with Milton Friedman who said "The FDA has done enormous harm to the health of the American public by greatly increasing the costs of pharmaceutical research, thereby reducing the supply of new and effective drugs, and by delaying the approval of such drugs as survive the tortuous FDA process.” Recently, it has been claimed by other economists that formal studies of the costs and benefits of FDA regulations are largely lacking from the economics literature.

FDA baised towards preventing "visible" casualties
Nobel prize-winning economist Milton Friedman says it is highly publicized when a drug the FDA approves is later found to be harmful, but that we do not hear much about drugs that the FDA has prohibited. And, has says, we do not hear about the individuals who have died because the FDA has prohibited or delayed a drug from coming to market. Friedman says that because of the public disgrace that FDA faces when it is found to have approved a dangerous drug, the FDA has a natural tendency to more concerned with not approving a dangerous drug than to be concerned with not making the error of keeping beneficial drugs from coming to market. He says, they will take "any chance whatsoever" to keep from approving a dangerous drug, including the chance that it may be causing more harm by keeping beneficial drugs from coming to market. He explains, "what if you make the mistake of failing to approve a drug that could have saved thousands of lives. Who will know? The people whose lives might have been saved will not be around. Their relatives are unlikely to know that there was something that could have saved their lives. A few doctors, a few research workers, they will be disgruntled, they will know. You or I, if we were in the position of that bureaucrat, we'd behave exactly the same way. Our own interests would demand that we take any chance, whatsoever, almost, of refusing to approve a good drug in order to be sure that we never approve a bad one.". The error of approving a harmful drug is referred to is a "Type I error" (and the lives lost is a "Type I cost"). The error of preventing a beneficial drug from coming to market is called a "Type II error" (and the lives lost is a "Type II cost"). This is illustrated in the following chart:

In 1974, FDA Commisioner Alexander Schmidt agreed that individuals in the FDA are under more scrutiny to avoid Type I errors than Type II errors. He said: "In all of the FDA’s history, I am unable to find a single instance where a Congressional committee investigated the failure of FDA to approve a new drug. But, the times when hearings have been held to criticize our approval of new drugs have been so frequent that we aren’t able to count them… The message to FDA staff could not be clearer. Whenever a controversy over a new drug is resolved by its approval, the Agency and the individuals involved likely will be investigated. Whenever such a drug is disapproved, no inquiry will be made." However, in the 1980's the FDA did suffer some criticism for delaying approval of AIDS drugs. When patient advocacy groups get media coverage, the FDA responds because "they make the consequences of delay and rejection more visible."

Friedman's proposed solution to diminishing Type II costs (harm from disallowing a beneficial drug) involves the abolition of the FDA as a whole. His opinion is that the bias involved in these deaths in intrinisic to compulsory regulation and more people are harmed than helped by compulsory regulation of drugs. He proposes to replace it with voluntary regulation from private certifiers (and says these would be somewhat analagous to Underwriters Laboratories for electrical equipment), with individuals having the free choice to take approved drugs or unapproved drugs (as long as they have the knowledge that they are unapproved) in accordance with their own risk-aversion standards.

Allegations regulation harms patients through lack of options
The FDA recognizes that "safety" depends on the potential benefits of a drug, so if a drug with serious side effects can be used to treat a deadly disease it would be approved more easily than a drug with the same side effects to treat a minor ailment. However, Austrian school economist Robert Higgs says that the FDA does allow it to be taken into account that each individual has his own standards of approval in regard to what risks he is willing to take in light of possible benefits, and, instead, imposes its own risk-avoidance preferences on the consumer. Taking this into account, Higg's analysis concluded that "the FDA's regulation of drugs (and likewise its regulation of medical devices), both general and in several of its specific forms, has deterimental effects on consumers' welfare, with consumer welfare being "properly understood" as consumers' prospective and subjective marginal utility.

A national survey of neurologists and neurosurgeons performed by The Polling Company by commission of the anti-regulation Competitive Enterprise Institute in 1998 (after the passage of the FDA Modernization Act of 1997) revealed that 67% of them believe that the FDA takes too long to approve new drugs and medical devices. 73% of them believe that unapproved drugs and devices should be made available to them provided there is a warning lable indicating the unapproved status. 58% agree that the approval process costs lives. 80% of them say that on at least on occation that the approval process has prevented them from treating their patients with the best possible care.

Regulation allegedly slows drug development excessively
Prior to passage of the Kefauver Harris Amendment of 1962, the average time from the filing of an investigational new drug application (IND) to approval was seven 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. FDA critics such as Nobel prize-winnning economist Milton Friedman acknowledge that the lengthy FDA approval process has saved lives in individual cases, such as that of thalidomide, but argue that "there's enormous evidence that they have caused more deaths by late approvals than they have saved by early approval." Not all scholars agree that economists have substantially addressed this issue however. In 2005, the authors of a new economic methodology for evaluating the effects of changes in FDA approval time wrote "very little quantitative empirical evidence has been put forward to evaluate the degree to which the speed and safety tradeoff facing the FDA is being resolved efficiently." The authors added that they were aware of only a single prior economics study that methodically attempted to address this issue, and it dated to 1973.

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 of 1990, Dr. 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 procedures to expedite approval of drugs for life threatening diseases, and exanded 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 just two years later in 1987. Three of the first five drugs targeting HIV were approved in the United States before they were approved in any other country.

"Proof of Efficacy" requirements increases prices of drugs unnecessarily
Studies published in 2003 by Joseph DiMasi and colleagues estimated an average cost of approximately $800 million to bring a new "first-in class" drug to market, while a 2006 study estimated the cost to be $500 million to $2 billion. The consumer advocacy group Public Citizen, using a different methodology, estimated the average cost for development of all new drugs to be under $200 million, about 29% of which is spent on FDA-required clinical trials. Dimasi himself rejects the claim that high drug development costs are responsible for high drug prices. As he wrote in a published letter, "At the time that drug prices are determined, the associated R&D spending for a drug is a sunk cost. Basic economic logic tells us that R&D costs do not determine prices."

In contrast, Nobel prize winning economist Gary S. Becker has written that FDA-required clinical trials for new drugs do contribute to high drug prices for consumers. Prior to the passing of the Kefhauver-Harris Amedment, drugs were required to obtain FDA certification only for safety. That 1962 amendment introduced new regulations went beyond safety standards and required that drugs be proven to be effective, as well, to the FDA. Rejecting government-imposed price controls as a solution to lowering prices, Becker advocates eliminating the regulations introduced in 1962, which would make drugs cheaper to bring to market. He says that this reduced cost in bringing drugs to market will increase the introduction of new drugs, especially from small biotech firms that do not have the capital to invest in extended efficacy trials. Becker says that this will result in more drugs coming to market to compete with each other and will therefore result in lower prices. He says though efficiacy trials would not be mandatory, "fear of lawsuits and the desire to maintain a good reputation would sometimes induce companies to conduct many trials before marketing highly invasive medicines." Another way of saying this is that costly regulations create a barrier to entry for lesser capitalized firms, resulting in less competition in the field. According to one study, the approval process doubles the cost of developing a new drug.

FDA approval procedures negatively affect research and development cycle
A study by Steven N. Wiggins compared pre-1962 data with date after 1962 through the 1970's and found that the 1962 regulations drastically reduced the number of new drugs introduced as well as reduced the amount of research spending. They found that regulations have reduced the rate of introduction of new drugs by 60%. They find a "steep trade-off" between requiring greater certainty about a drugs effectiveness and the rate of new drug introductions.

Importation regulations increase costs
Some claim that the FDA unjustly opposes importation of cheaper drugs from foreign sources, which is held to be an anti-competitive policy that keeps drug prices artificially high in the United States. Prices of almost all pharmaceutical drugs in Europe are significantly lower than in the United States.

Representatives of the pharmaceutical industry, which supports importation restrictions, respond that the lower prices are often due to government imposed price caps, not because of "competition" between markets.

FDA is slow in granting over-the-counter status
An article in the libertarian magazine Reason argued that the FDA should be more aggressive about switching medications to over-the-counter status. They argue that the prescription requirement causes consumers to spend time and money on unnecessary doctor's visits. In the past, the FDA has lagged behind regulator agencies in other major industrialized nations in switching drugs from prescription to over-the-counter status. Unlike some nations, the U.S. does not have a pharmacist-dispensed "behind the counter status" for drugs which are not yet deemed appropriate for over-the counter status, but which do not require a doctor visit for safe and effective usage by patients.

FDA advertising restrictions violate First Amendment and/or causes unnecessary deaths
Some critics argue that FDA restrictions on speech in drug marketing are harmful or unconstitutional. The drug propranolol was approved in 1968, but was not specifically indicated for the treatment of angina or hypertension until 1973 and 1976 respectively, despite earlier evidence that it might be beneficial in these conditions. A study by Arthur D. Little estimated that approximately 10,000 American died every year that the FDA prohibited manufacturers from disseminating information about these uses, including sending copies of peer-reviewed studies to doctors and advertising. When folic acid was recommended to reduced birth defects by the Centers for Disease Control and Prevention in 1992, the FDA immediately announced that it would prosecute any food or vitamin manufacturer that placed the CDC recommendation in its advertising or labeling.

The FDA has also been criticized for prohibiting dietary supplement manufacturers from making "drug claims" on the labels of their products. Manufacturers of supplements (which are considered foods for regulatory purposes) are allowed to make only limited claims regarding how the supplement affects the structure or function of the body (structure/function claims), and are prohibited from stating that the supplement can prevent, cure, or mitigate a disease or condition.

One critic, Representative Ron Paul (R-TX), introduced a bill on November 10 2005 titled the "Health Freedom Protection Act " (H.R. 4284), which proposes to stop "the FDA from censoring truthful claims about the curative, mitigative, or preventative effects of dietary supplements, and adopts the federal court’s suggested use of disclaimers as an alternative to censorship. Other critics, such as the Life Extension Foundation, claim that the prohibitions are a violation of the Constitutional right to free speech.

The FDA also prevents providers of foods from making certain "drug claims." For example, the FDA threatened legal action against cherry juice manufacturers for labels with claims such as "If you're plagued with chronic pain of arthritis, headaches, or even gout, pros say a daily bowl of cherries could ease your ache without side effects," and "cherries are packed with... a natural chemical that not only flushes cancer-causing substances out of the body but also helps stunt the growth of cancerous cells." The FDA has sent letters to cherry distributors saying that when health benefits are mentioned, the cherries then become "drugs" that, among other enforcement actions, are subject to "seizure."

Under-regulation
In contrast to those who see the FDA as a source of excessive regulation, other critics believe that the FDA does not regulate 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 labelling, and allows the use of dangerous agricultural chemicals, food additives, and food processing techniques.

Allegedly releases unsafe drugs
Some critics believe that the FDA has been too willing to overlook safety concerns in approving new drugs, and is slow to withdraw approved drugs once evidence shows them to be unsafe. Troglitazone and rofecoxib (trade name Vioxx) 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. Faced with numerous lawsuits, the manufacturer voluntarily withdrew it from the market in 2004. The example of Vioxx has been prominent in an ongoing debate over whether new drugs should be evaluated on the basis of their absolute safety, or their safety relative to existing treatments for a given condition.

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. 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 a FDA scientific document."

In 2006, a committee was appointed by the Institute of Medicine to review pharmaceutical regulation in the U.S. and to issue reccomendations for improvements. The committee was composed of 16 experts, including leaders in clinical medicine, medical research, economics, biostatistics, law, public policy, public health, and the allied health professions, as well as current and former executives from the pharmaceutical, hospital, and health insurance industries. The authors 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 independance of the FDA.

Approved unsafe additives and packaging procedures in foods
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 which may hide signs of spoilage from the consumer. The irradiation of food for purposes of safety and longer shelf life is regulated by the FDA. The FDA has concluded that such irradiation is safe, but places a consumer advisory label on all irradiated food.

The FDA has been criticised 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 signalling is thought to play a role in sustaining the growth of some tumors, although there is little or no evidence that exogenously absobed 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 moratorium on rBGH use in dairy cattle.

The FDA has also been criticised for permitting the routine use of antibiotics in healthy domestic animals to promote their growth, a practice which 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. However, many studies of these compounds have failed to demonstrate heath risks. For example, a Japanese group found in 1987 that tartrazine was not carcinogenic even after being fed to mice for two years. In addition, a German group found in 1989 that Sunset Yellow did not induce mutations that could lead to cancer in laboratory animals.

Pharmaceutical industry has too much influence over the FDA
Critics have disputed the claim that the Prescription Drug User Fee Amendment has improved the speed of drug approvals. The advocacy group Consumer Union has claimed that the primary effect of this program has been to increase the influence of the pharmaceutical industry on FDA policy, similar to the effect meat industry user fees have had on the USDA. In contrast, a 2005 analysis published by economists at the National Bureau of Economic Research estimated that the PDUFAs produced a welfare benefit of billions of dollars to producers, and saved hundreds of thousands of patient life-years through more rapid drug approvals.

A 2005 investigation by reporters from the prestigious science journal Nature found that 70% of FDA panels writing clinical guidelines on prescription drug usage contained at least one member with financial links to drug companies whose products were covered by those guidelines. In the most egregious instance, every member of a panel which recommended the use of epoeitin alfa in HIV patients had received money from a manufacturer of that drug. On March 21, 2007, the FDA announced new guidelines for disqualifying experts from serving or voting on advisory committees if they had received financial compensation from a drug company potentially affected by the committee's recccomendations.

The FDA has been criticized regarding its delayed approval of foreign drugs to protect the US pharmaceutical companies from foreign competition. Eli Lilly's Fluoxetine was the first SSRI to be approved by the FDA. Kali-Duphar, the Dutch manufacturer of another antidepressant fluvoxamine, had first attempted to apply for FDA review in the early 1980s (much earlier than Eli Lilly) but fluvoxamine was not approved until the rights were bought by the US pharmaceutical company Reid Rowell. Critics have suggested that the FDA was attempting to protect Eli-Lilly's fluoxetine so it could gain a foothold in the US market before approving fluvoxamine.

FDA discriminates based on sexual preference in blood donations
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. The issue has been periodically revisited by the Blood Products Advisory Committee within the FDA Center for Biologics Evaluation and Research. Documentation from these meetings is available.