New advertising code of conduct established in Vioxx withdrawal fallout
Summary
Recent high-profile drug withdrawals have resulted in a new code of conduct to govern direct-to-consumer advertising. As more and more drugs are likely to come under regulatory and public scrutiny, the pharmaceutical industry will need to employ effective marketing and education strategies to ensure patient and physician confidence is retained and the impact of drug safety scares is minimized.Concerns over drug safety and products being withdrawn due to adverse events or risks of serious side effects are not just a recent phenomenon. In fact, they can be traced back as far as the early 20th century, when the use of pharmaceuticals to cure and relieve disease began to gain momentum.
Over 30 drugs have been withdrawn from the market in the last 20 years, with many more receiving 'black box' warnings or other restricted prescribing. However, the withdrawal of Merck & Co's painkiller Vioxx (rofecoxib) in September 2004 brought the issue of drug safety to the forefront and has had a resounding impact on both the way new drugs are reviewed and advertised, and on post-approval safety surveillance techniques and systems.
The withdrawal of Vioxx had several significant and far-reaching impacts. For Merck, the loss of one of its major blockbuster products not only left a large hole in its revenue stream, but also led to a considerable fall in the company's share price, leaving it vulnerable to potential takeovers. Moreover, Merck is fighting over 1,000 product liability lawsuits, with varying success - a jury found in favor of the plaintiff and awarded her $250 million in damages, while another found in favor of Merck and dismissed the case.
In addition, the FDA's approval and safety surveillance processes were seen as ineffective and many accused the agency of being too closely linked with the companies it was meant to be regulating. Furthermore, the promotion and marketing of drugs, particularly through direct-to-consumer channels, was highly criticized and has been the subject of several reforms throughout 2005.
The impact of drug safety scares
Since 1995, over 15 drugs have been permanently withdrawn from the market due to safety reasons, with numerous others having been suspended or removed in certain markets only. However, few of these withdrawals have had the same impact as that of Vioxx.
Problems with drugs such as Sankyo and Parke-Davis' Rezulin (troglitazone) and Bayer's Baycol (cerivastatin) for example, have had little effect on the blockbuster potential of competitor products. In contrast, the withdrawal of Vioxx has led to a severe decline in sales of Pfizer's competitor product Celebrex (celecoxib) and led to a review of the safety of all the COX-II inhibitors, resulting in the removal of Pfizer's other product, Bextra (valdecoxib), from the market.
There are several factors that affect the impact of a drug safety scare, the most crucial of which being the severity of condition and the chronicity of treatment. Therapies for the treatment of life-threatening or severely debilitating diseases such as HIV and cancer are, for the most part, associated with unpleasant and sometimes serious side effects. However, most patients accept the adverse side effects as these treatments both prolong and improve their quality of life. In contrast, if the risk of side effects is perceived to outweigh the therapeutic benefit provided by the product, use is often restricted or the drug is withdrawn from the market.
There is a much lower threshold for side effects experienced with drugs that are used for the relief of everyday illnesses, asymptomatic diseases or for chronic conditions which are perceived as non-life threatening. As such, safety issues with drugs for the treatment of diseases such as dyslipidemia, diabetes, arthritis and several CNS disorders are more likely to result in a withdrawal or restricted prescribing than those that are used in life-threatening or acute illnesses.
The size of the affected patient population is also critical in assessing the potential impact of a drug safety scare. In February 2005, Elan and Biogen's multiple sclerosis drug Tysabri (natalizumab) was voluntarily taken off the market after it was believed to be responsible for the deaths of two patients. However, given the size of the niche market that it was used in, the withdrawal did not garner the same publicity as the withdrawal of Vioxx. Although the share price of the manufacturers initially fell, the companies conducted additional trials and are now looking to re-launch the product.
In contrast, safety issues with products that are used widely in the general population and highly visible through marketing have been heavily covered in the media - feeding public concern and prolonging the safety scare.
In addition, the larger a patient population, the more likely that adverse events that appeared in insignificant numbers of patients during trials will become significant in the greater population.
It is estimated that over 100 million people were prescribed Vioxx, leaving almost 30 million at risk of serious cardiovascular problems, whereas less than 100 people were believed to be at risk of a severe adverse event with Tysabri.
More effective communication required
Direct-to-consumer (DTC) advertising was singled out as a key factor contributing to the impact of the Vioxx withdrawal, as it led to a more significant patient population being prescribed the drug than was appropriate. The intense DTC campaigns undertaken by Pfizer and Merck - with an annual DTC spend of over $150 million for Vioxx and Celebrex combined - led to many patients being prescribed the drugs after seeing them advertised, despite not being at risk of adverse gastrointestinal effects from other painkillers. Furthermore, the intensity of the COX-II marketing campaigns so soon after the products' launches was also criticized with many saying the drugs were too widely advertised before their true side effect profiles were known.
Consequently, the use of DTC advertising underwent considerable review throughout 2005, and resulted in the organization PhRMA devising a new code of conduct for the promotion of drugs through this medium. Some companies have taken additional steps, with Bristol-Myers Squibb announcing a ban on DTC for 12 months after a new drug enters the market, instead using this time to educate physicians about the product. Pfizer adopted a similar six-month ban.
There has also been a shift towards direct-to-patient advertising, where the focus is on patient retention rather than acquisition. Several new adverts have appeared with a more educational theme, encouraging patients to visit their physicians to discuss the disease and its management rather than specific products.
Alternative media, in particular the internet, are also being explored as marketing tools, reducing the emphasis on the highly visible television adverts and enabling patients to take a more interactive role in researching their disease and treatment options.
With the reduction in DTC and the increased emphasis on safe use of pharmaceutical drugs, ensuring that the physician is fully educated about a new product will be crucial to its uptake. Moreover, encouraging a continuous dialogue with pharmaceutical companies, be it through face-to-face visits or online tools, will enable physicians to discuss any problems or queries they have with the drug. In addition, a move away from purely promotional contact to a more educational focus will restore the credibility of the industry with physicians, which has suffered in the wake of the drug safety scares experienced over the last decade.
The withdrawal of Vioxx and the subsequent increased scrutiny of other drugs means the availability of comprehensive safety data will be fundamental to ensuring the commercial success of new products. Although pharmacovigilance and marketing have traditionally been uneasy bedfellows, drug safety information can be used as an effective promotional tool.
Open and transparent communication of any potential safety problems to both patients and physicians ensures that adverse events are not unexpected and, therefore, their impact is minimized. Moreover, addressing these data in all marketing campaigns could prove to be beneficial in ensuring patient and physician confidence in pharmaceutical products.
Several companies have included safety messages in their marketing materials after competitor products have been affected by safety scares. In the future, this is expected to become a routine marketing strategy rather than a risk management tool.
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