by Donald W. Light

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,1 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.2 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.34 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.5 6 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.7

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.8 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.9

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?

Advice to readers: Experienced, independent physicians recommend not to take a new drug approved by the FDA until it is out for 7 years, unless you have to, so that evidence can accumulate about its real harms and benefits.10

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Disclaimer: The assessment and views expressed here are solely the author’s and do not necessarily reflect those of persons or institutions to which he is associated. The comments and suggestions of Gordon Schiff, an expert in prescribing at Brigham and Women’s Hospital, and Robert Whitaker are gratefully acknowledged.

References

1. Lexchin J. New drugs and safety: what happened to new active substances approved in Canada between 1995 and 2010? Archives of Internal Medicine 2012 (Nov 26);172:1680-81.

2. Hilts PJ. Protecting America's Health: The FDA, Business and One Hundred Years of Regulation. New York: Alfred A. Knopf; 2003.

3. Rodwin M. Conflicts of interest, institutional corruption, and Pharma: an agenda for reform. Journal of Law, Medicine & Ethics 2012;40:511-22.

4. Rodwin M. Reforming pharmaceutical industry-physician financial relationships: lessons from the United States, France, and Japan. Journal of Law, Medicine & Ethics 2011(Winter):2-10.

5. Sismondo S. Ghost management. PLoS Medicine 2007;4:1429-33.

6. Sismondo S, Doucet M. Publication ethics and the ghost management of medical publication. Bioethics 2010;24:273-83.

7. Schondelmeyer S, Purvis L. Rx Price Watch Report. Washington DC: American Association of Retired Persons 2012.

8. Kozauer N, Katz R. Regulatory innovation and drug development for early-stage Alzheimer's disease. New England Journal of Medicine 2013 (Mar 13);DOI: 10.1056/NEJMp1302513

9. Young JH. The Toadstool Millionaires: a social history of patent medicines in America before federal regulation. Princeton, NJ: Princeton University Press; 1961.

10. Schiff G, Galanter W, Duhig J, et al. Principles of conservative prescribing. Archives of Internal Medicine 2011;171:1433-30.