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