Some facts about the industry and the people they serve: In the UK, the pharmaceutical trade

is the third most profitable activity after finance and - this will surprise you if you live here - tourism. We spend 7bn a year on pharmaceutical drugs, and 80% of that goes on patented drugs - medicines released in the last 10 years. In 2002, the 10 US drug companies on the Fortune 500 list had combined international sales of $217bn Americans spend over $200 billion on prescriptions drugs with a growth of 12% annually. The rising cost of drugs means that many Americans simply cant afford them or take less than the prescribed dose and are too embarrassed to tell their treating doctor, therebye making an accurate assessment impossible. The elderly are the most vulnerable without supplementary insurance, and an average cost of $1500 a year for each drug they take, the costs are an impossible burden for many seniors. Despite the drug industrys claims, research and development accounts for a relatively small part of their costs, especially when compared with marketing and administration, which soaks up about 36% of sales revenue 250% more than R&D. In 2001, the former chairman and CEO of Bristol-Myers Squibb, Charles A. Heimbold Jr. made just under $75 million on top of $76 million in unexercised stock options (Families USA). Many of the new innovative drugs are developed not by the drug companies, but by universities, biotech firms or the NIH this is largely tax-payer funded research. The vast majority of drugs marketed as new drugs are me too drugs essentially a new name, packaging and marketing pitch is the only real difference for example, the many cholesterol lowering drugs on the market. IMS Health estimated in 2006 that the worldwide sales of prescription drugs was around $643 billion with U.S sales accounting for half of that figure. Pfizer makes $50 billion a year. Americans pay much more for prescriptions drugs than virtually any other country in the world sometimes hundreds of percent more. Amongst the crimes committed by big pharma are illegally overcharging Medicaid and Medicare, paying kickbacks to doctors, anti-competitive pricing practices, clandestine deals with generic companies to keep cheap generic drugs off the shelves, promoting the use of drugs not approved for certain ailments, misleading advertising and hiding evidence of wrong doing. Civil and criminal fines barely make a dent in the companys earnings. Mercks drug Vioxx killed about 60,000 patients about the number of Americans killed in the Vietnam War. This claim was made by David Graham of the FDA, much to the disgruntlement of his FDA bosses Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer. When trials throw up results that companies dont like,

they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drugs true effects. Regulators see most of the trial data, but only from early on in a drugs life, and even then they dont give this data to doctors or patients, or even to other parts of government. This distorted evidence is then communicated and applied in a distorted fashion. In their forty years of practice after leaving medical school, doctors hear about what works ad hoc, from sales reps, colleagues and journals. But those colleagues can be in the pay of drug companies often undisclosed and the journals are, too. And so are the patient groups. And finally, academic papers, which everyone thinks of as objective, are often covertly planned and written by people who work directly for the companies, without disclosure. Sometimes whole academic journals are owned outright by one drug company. Aside from all this, for several of the most important and enduring problems in medicine, we have no idea what the best treatment is, because its not in anyones financial interest to conduct any trials at all. These are ongoing problems, and although people have claimed to fix many of them, for the most party they have failed; so all of these programs persist, but worse than ever, because now people can pretend that everything is fine after all. Manufacturers want their drugs approved as quickly as possible (the patent clock is ticking) so often ask to measure what are called surrogate indicators, which are proxies for hard indicators which are the outcomes we are really interested in. For example, blood pressure, or cholesterol measures may be the endpoint measured in a clinical trial, rather than a more meaningful indicator like heart attack, stroke, or death. Measuring surrogates is easy. Measuring hard outcomes is time consuming and could mean the need to study hundreds more patients. When surrogates are demonstrably accurate predictors of hard outcomes, were in a good place its fair to use a short, smaller trial. But assuming a surrogate predicts a hard outcome can lead to bad decisions. The classic example is the CAST trial, which tested a group of heart drugs for their ability to control abnormal heart rhythms the surrogate. But the trial also measured hard outcomes. And the trial answered the question the surrogate improved, but the treatments were killing, not helping patients. Goldacre gets into the problem with so-called me-tos which are variations of a competitors drug product. For example, there are several different but similar statin drugs on the market, as there are a group of similar drugs for blood pressure called ACE inhibitors. The typical pharma criticism is to berate industry for lacking innovation and playing it safe. But this is a view shaped by an ignorance of the pharmaceutical development process. First, these drugs are often all in development at the same time. Once a potential pathway or drug target has been identified, its a race to design drugs, complete the trials and be first on the market. And until the trials are done, and the drugs are approved, its anyones guess which is going to be the new drug and which will be the me-too. So we may have a dozen or more similar drugs on the market. Thats a consequence of a competitive marketplace. I share Goldacres mixed feelings about me-toos. This kind of variety is useful to patients who may prefer one over another. Yet its also true that the pharmaceutical industry really doesnt compete on price, nor does it regularly conduct head-to-head trials comparing drug A versus drug B. So we end up with markets where theres

little clear information on which drug is best, and worst of all, no price competition, which would at least reduce the costs of treatment. Goldacre points out the pressing need for comparative effectiveness research, studies which compare treatments and help us determine which is superior. One of the most important roles of a regulator is the requirement to monitor its safety after approving it for sale. Given a drug is usually tested in small numbers of patients who are carefully selected and closely monitored, there can be a number of surprises once a drug is unleashed on a market. I covered a lot of this ground in a prior post on adverse event reporting. Goldacre spends time describing how regulators worldwide do a generally poor job of both collecting safety information, but also sharing it with health professionals and the public. Some of the recommendations he has to improve regulation includes: requiring companies to compare new drugs against the current standard of care rather than placebo raising the evidence bar to demand trials that answer more relevant questions useful for patients and physicians dramatically increasing the transparency of drug evaluation process, so that the evidence supporting decisions can be evaluated improving the way we share information on the risks and benefits of drugs All of these solutions are achievable. Transparency and data access are obvious. There is little cost and tremendous upside. Changing the standards for clinical trials would have a much more profound effect on drug development, possibly delaying new drugs for years. Goldacre argues this is justified were not losing out if theres no evidence to demonstrate that the new treatment is better than the current standard. Its an important policy issue which merits discussion. The patient wants the best treatment, and generally trusts the physicans decisionmaking. Their opinions may have been influenced by direct-to-consumer advertising. In some cases, they may believe they are ill because of advertising. Costs of treatment may or may not be a concern, depending on insurance coverage. The physician prescribes the drug. The decision making process for physicians is not always rational, or evidence-based. They may have been exposed to biased sources of information about a drugs merits. The cost of the drug may not be known and the physician may not care. The pharmacist has verify the safety and appropriateness of the drug, but well after the treatment decision has already been made. The question of who pays has to be sorted out. There is usually little opportunity to help guide drug selection. The pharmacist may also be a target of direct marketing from pharmaceutical companies. The insurer (private, government, or otherwise) will often know little about the individual patient circumstances. They generally want the same thing as the patient the most appropriate therapy but know the cost of each treatment and will have a preference for using more cost-effective treatments first.