In a paper presented in August at the 105th Annual Meeting of the American Sociological Association, Dr Donald Light, a professor of comparative health policy at the University of Medicine and Dentistry in New Jersey, revealed that the drug industry is a "market for lemons"-one in which the seller knows much more than the buyer about the product, and takes advantage of the fact.
"Sometimes drug companies hide or downplay information about serious side-effects of new drugs and overstate the drugs' benefits," Light said. "Then, they spend two to three times more on marketing than on research to persuade doctors to prescribe these new drugs. Doctors may get misleading information and then misinform patients about the risks of a new drug. It's really a two-tier market for lemons."
Light's paper-Pharmaceuticals: A Two-Tier Market for Producing 'Lemons' and Serious Harm-listed three main reasons why most new drugs on the market-85 per cent of them-are lemons.
First, there are no independent studies. The drug-makers themselves are responsible for testing their own creations and, not surprisingly, these tests are often "incomplete, partial, substandard clinical trials". In one evaluation of 111 final applications for approval, 42 per cent lacked properly randomized trials, 40 per cent used flawed testing techniques for dosages, 39 per cent had no evidence of clinical effectiveness, and 49 per cent came with serious adverse side-effects.
Second, Big Pharma is given an undue amount of legal protection, allowing drug companies to get away with hiding information on a drug's lack of efficacy or its potentially dangerous risks. One case in point is Avandia, once the world's best-selling antidiabetes drug. Reports now suggest that its manufacturer, Glaxo-SmithKline, withheld information about Avandia's potentially deadly side-effects. Yet, despite the clear evidence of doing harm, the drug is still on the market (see box, page 7).
Third, Light also points out that the bar to establish drug effectiveness is set fairly low to make it easier for companies to get their new drugs approved. Instead of using currently approved drugs as benchmarks of efficacy, the present testing system determines whether or not new drugs work by comparing their effects with placebos. In fact, systematic reviews show that just one in seven new drugs is superior to drugs already available on the market (Health Aff [Millwood], 2007; 26: 1793-4).
Little benefit, lots of risk
Light's alarming revelations are based on a range of independent sources and studies, including the Canadian Patented Medicine Prices Review Board, the US Food and Drug Administration (FDA) and Prescrire International-a French language journal that publishes extensive research on pharmacology, toxicology and pharmaceuticals. Much of the research had been carried out for a book, edited by Light, that will be published later this year called The Risk of Prescription Drugs (New York, NY: Columbia University Press, 2010). In it, he describes how studies over the past 40 years demonstrate that most new drugs offer few clinical advantages over currently existing ones. However, as newly patented drugs offer higher profits, drug companies tend to manipulate the data to maximize evidence of effectiveness and minimize evidence of possible dangers. As a result, Light explains, "[P]atients are exposed to a greater risk for hidden side-effects as the public body designed to protect them [the FDA] approves new drugs as 'safe and effective' that, from a clinical or patient's point of view, may not be either." Indeed, many drugs subsequently prove dangerous enough to end up requiring warnings, restrictions or complete removal from the market.
The increasingly high rates of adverse drug reactions (ADRs) reflect just how big a problem this has become. A review of studies in 1998 concluded that more than 2.2 million hospital patients had experienced a serious ADR in the US in 1994, and an estimated 106,000 died, making ADRs the fourth leading cause of death. Today, the rates are thought to be substantially higher. Indeed, the number of ADRs reported to the FDA nearly tripled between 1995 and 2005, and there is no indication that this increase will be levelling out any time soon. Assuming a constant reporting rate, ADRs are rising by around 15 per cent every year.
Fortunately, many of us-and particularly WDDTY readers-are now aware of the wide range of safe and effective alternatives to prescription drugs. However, if a drug is your only option, remember that newer doesn't always mean better or safer.
A prime example of a drug 'lemon' is GlaxoSmithKline's Avandia (rosiglitazone), approved 10 years ago to treat type 2 diabetes. It quickly became the world's best-selling diabetes drug, earning billions for GSK. However, fortunes changed in 2007 when a study was published that linked the drug to a 43-per-cent increased risk of heart attack and a 64-per-cent greater risk of death due to cardiovascular causes (N Engl J Med, 2007; 356: 2457-71). It's been estimated that Avandia caused over 83,000 heart attacks between 1999 and 2007.
Worse, GSK knew about these risks years before the evidence was made public, but instead of warning patients and regulatory bodies, it "intimidated indepen-dent physicians, focused on strategies to minimize findings that Avandia may increase cardiovascular risk, and sought ways to downplay findings that the rival drug Actos (pioglitazone) might reduce cardiovascular risk" (Committee on Finance, United States Senate. Staff report on Glaxo-Smith Kline and the diabetes drug Avandia, 2010, http://finance. senate.gov/newsroom/chairman/release/?id=bc56b552-efc5-4706-968d-f7032d5cd2e4).
Nevertheless, even before Avandia's approval, there were concerns over the paucity of evidence to support its use. In comments sent to Europe's drugs regulator, the European Medicines Agency (EMA), one expert advisor noted that Avandia had no long-term studies with hard primary endpoints-the results that determine whether or not the treatment has worked. The same advisor also questioned whether a drug should be put on the market without such data, and was unconvinced that Avandia had any advantages over agents already available.
Another advisor noted that safety issues-including possible cardiovascular effects-were evident in the data from GSK (known as SmithKline Beecham then), and suggested postponing approval until better data were available. Yet, despite no new evidence being supplied, the drug was approved in 2000 (BMJ, 2010; 341: c4848).
According to Silvio Garattini, director of the Mario Negri Institute for Pharmacological Research in Milan and a member of the EMA panel that approved Avandia, the drug got through because of its "large commercial interest", showing that European regulators are just as guilty as the FDA when it comes to putting profit before patients.
At the time of writing, although Avandia has been recommended for withdrawal in both the UK and US, the drug remains on the market and is still being prescribed by doctors (www.bbc.co.uk/news/health-11170878).
WDDTY VOL. 21 ISSUE 7