There are concerns that pressures on regulators to approve new drugs more quickly have reduced the focus on patient safety, and this problem is exacerbated by new efficiencies in drug marketing which can quickly expose large numbers of patients to unknown risks, warns a researcher writing in this week’s British Medical Journal (BMJ).
New medicines which receive approval by the US Food and Drug Administration (FDA) up to two months before the deadline set for a decision are more likely to be subsequently withdrawn from the market on safety grounds or to have to carry safety warnings, writes David Kao, fellow in cardiovascular medicine at the University of Colorado Health Sciences Center, USA in the current BMJ (BMJ 2008;337;a2591).
For example, he says, it is estimated that 20 million patients were prescribed Merck & Co’s non-steroidal anti-inflammatory drug (NSAID) Vioxx (rofecoxib) over five years before it was taken off the market, and events attributable to the drug “may number in tens to hundreds of thousands.”
Dr Kao points out that, as a result of the US Prescription Drug User Fee Act (PDUFA), FDA approval times for new drugs more than halved, from an average of 33.6 months during 1979-86 to 16 months by 1992-2007. Moreover, regulators in the USA, European Union (EU) and UK are “somewhat dependent on the industry for funding,” given that user fees account for 43% of the FDA’s drug oversight budget, 75% of European Medicines Agency (EMEA)’s funding and 100% of that for the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), he says.
At the same time, drugmakers’ marketing techniques are now so sophisticated that a new product can be released onto websites within 90 minutes of being granted approval, says Dr Kao, and he calls for these techniques to be used to improve post-marketing surveillance and adverse drug reaction reporting.
However, industry and regulators have been quick to deny that faster approvals are creating risks for patients. Ken Johnson, senior vice president at the Pharmaceutical Research and Manufacturers of America (PhRMA), said that Dr Kao’s paper “suffers from a number of flawed assumptions, among the most glaring that FDA deadlines for approving drugs have shifted the agency’s focus away from patient safety.”
“While PDUFA does carry timeframes for the completion of a review, the FDA can, and repeatedly has, returned to the sponsor with further questions about safety or efficacy that ultimately lengthen the review time. The fact remains that experts’ analysis – including a paper published in 2007 by the New England Journal of Medicine – showed no increase in the overall rate of safety recalls after the user-fee system was introduced” said Mr Johnson.
Moreover, he added, it is “erroneous to conclude that marketing plays a dominant influence on which medicines physicians to prescribe.” A survey this year of 501 physicians conducted by KRC Research found that peer-reviewed journal articles and information received from peers had more influence on physician prescribing decisions than industry marketing. “What’s more, only 8% of physicians usually prescribed a brand-name medicine, while 41% of doctors surveyed usually prescribed generic drugs,” said Mr Johnson.
Before any new drug is approved, it will receive “a very thorough review of its quality, safety and efficacy conducted by an appropriate regulatory agency,” adds a statement from the MHRA reported by the Press Association. In addition, the Agency notes that, “in the UK, new drugs will also be reviewed by the UK’s Commission for Human Medicines. Usually there will be questions posed to the applicant during the review, and only when the appropriate regulatory agency is satisfied that any significant issues are resolved, will approval be given. At the time of approval, the company will have an agreed risk management plan in place to ensure continued safety monitoring of the drug in clinical use in the market place.”
