How the Drug Companies Make Money by Ignoring Science

1. How the Drug Companies Make Money by Ignoring Science David Marcus December 1, 2004

2. Introduction • The pharmaceutical industry is one of the most visible and profitable industries in America • Success of drug industry and health of Americans rely on proper research and drug approval • FDA is responsible for ensuring that drugs are effective and safe • However, the system doesn’t always work. • Research and clinical trials are often biased • Drugs are often unsafe (e.g. Vioxx)

3. Introduction (cont.) • The drugs that slip through the cracks are often the result of poor research design and/or intentional bias • Many factors play a role, including political, social, financial. • For example, Bayh-Dole Act opened door for drug industry and academic medicine to work together. Many unintended consequences. • Overall, scientific process has been compromised, and action must be taken to restore trust in pharmaceuticals.

4. The Bayh-Dole Act • Before 1980, drug companies and NIH-funded labs could not work together • This was intended to prevent conflicts of interest • In 1980, the Bayh-Dole Act was passed and eliminated this rule • Bayh-Dole encouraged academic medicine to collaborate with industry in developing useful products • The Act was intended to stimulate industry and speed up “technology transfer”

5. Effects of Bayh-Dole • Blurs lines between science and industry • Huge benefits to pharmaceutical industry - can now use gov’t funded research to develop drugs • However, there are many negative consequences. • Agreements between drug companies and private labs are very lucrative for labs • For example, the Japanese cosmetic maker Shiseido gave Harvard’s Massachusetts General Hospital $180 million over ten years for first rights to discoveries by faculty dermatologists • Drug companies have significant power in determining research design, etc.

6. Improper Relationships • Lenient rules regarding individual researchers’ personal ties to pharmaceutical companies can introduce another source of bias in clinical trials. • Researchers serve as consultants to drug companies, enter into patent and royalty agreements, promote drugs, etc. Many have equity interests in the companies. • None of these associations are illegal; however, they obviously introduce potential conflicts of interest.

7. Improper Associations in the NIH • The NIH is the premier biomedical research body in the USA, and arguably the world • A 2003 report by David Willman showed that many NIH officials have outside associations with pharmaceutical companies • Potential conflicts of interest have implications in setting NIH priorities, designing clinical trials, and instituting research protocols

8. How is the research actually biased? • A recent survey found that industry-sponsored research was nearly four-times as likely to be favorable to the company’s product as NIH-sponsored research • There are a number of ways in which this bias can manifest itself

9. Omissions of data • Companies are not required to publish all data in research studies • Often, data that is unfavorable to a company’s product is left out of the published results of a study • This allows companies to paint a misleading picture about their product • Doctors and patients are unable to rely on accurate and complete data

10. Example: Celebrex • Celebrex is a medication made by Pharmacia (now part of Pfizer) used for treating arthritis pain • Company-sponsored study published in NEJM showed that Celebrex users showed fewer side effects than patients using two competitor drugs • Article in NEJM only included data from first six months of year-long study • In the course of the full study, there were no significant differences in side effects

11. Consequences of data omission • Companies can manipulate data to make almost any claims they want about their products • Researchers have little power to change the situation, as they are financially beholden to the drug companies

12. Ignoring Key Facts • Companies often ignore key warning signs about their products in order to maintain marketability • Potentially dangerous drugs make it to market or remain on the market due to failure to study risks

13. Example: Vioxx • Currently, Merck is facing investigations of failure to examine cardiovascular risks of Vioxx (recently taken off the market) • A significant amount of data indicated that Vioxx increased risk of cardiovascular disease in certain patients • Merck claimed that there was no marketing incentive to follow up on studies • Merck dismissed the studies, saying that they were not randomized or controlled • However, they did not initiate any studies to investigate possible risks • By ignoring risks, Merck endangered over 80 million people who had taken Vioxx

14. FDA responsibility for Vioxx • The FDA had the power to request that studies be done on the risks of Vioxx, but the agency balked • The FDA holds significant responsibility for the Vioxx debacle

15. Biased Comparisons • Drugs in comparative studies are often tested in nonequivalent doses • For example, a study of Pfizer’s Lipitor claims that it is more effective than the competitor drug Pravachol. • However, the study compared 80 milligrams of Lipitor to 40 milligrams of Pravachol. • Therefore, the results of the study are meaningless, but they have marketing potential

16. Testing against placebos • Aside from studies like the Lipitor/Pravachol comparison, there are very few comparative studies of drugs • Most drugs are tested against placebos • For a drug to be approved, it does not have to be proven to be any better than drugs already on the market • As a result, companies introduce more expensive drugs that aren’t necessarily better than the less expensive, older versions

17. Example: Nexium • Nexium is simply a purified form of the active form of Prilosec, the previous heartburn pill from AstraZeneca • Just before the patent ran out on Prilosec, AstraZeneca began heavily marketing Nexium in order to switch patients before generic competition arrived • The result is more expensive medication that is no more effective

18. How do drug companies convince doctors to prescribe more expensive drugs? • Companies disguise marketing as research via Phase IV clinical trials • Companies give doctors samples of drugs and ask for information on effectiveness of drugs • Not randomized, no controls…basically worthless studies • The real purpose is to get the doctors accustomed to using their drugs so that they will not prescribe less expensive generics

19. Conclusion • The drug companies are relentless in seeking profits, and they often compromise scientific integrity to achieve this goal • Regulations need to be considered to prevent bias from being introduced • For example, measures must be taken within the FDA and NIH to prevent conflicts of interest. • Companies must be held accountable for the fidelity of the scientific research that they sponsor. • If things aren’t changed, the American public’s trust in the pharmaceutical industry will continue to decline