Many see Vioxx and Avandia as clear signs that the drug safety system has failed. As soon as reports of these drugs' adverse
events began to flood the media, consumers—and Congress—demanded to know: "Why didn't we know sooner?"
Indeed, as we enter into the new Culture of Drug Safety, "knowing sooner" will be the call to arms. Companies, regulators,
and others will tap existing and new surveillance systems to generate more safety signals. It is likely that such systems
will improve the speed at which potential safety issues are spotted. However, even with these improved systems, understanding
what truly qualifies as a safety signal—and what's background noise—will take time, likely cause confusion, and in sum, not
be a magic bullet to solve the safety problem.
To move the safety system forward, we need to realize that it's not enough to know about drugs' risks—you also have to communicate
them. After all, for both Vioxx and Avandia, the drug surveillance system worked exactly as designed. With Vioxx, a clear
safety signal emerged after the VIGOR study, a 5,000-patient randomized active-controlled clinical trial that showed Vioxx
to be riskier than the control drug naproxen. But from that trial, Merck still needed to "qualify the signal" to understand
if Vioxx was increasing the risk of myocardial infarction or if naproxen was suppressing the risk. This required a placebo-controlled
study of about 2,000 patients over a two-year period, the APPROVe trial. Once that trial started, the difference between Vioxx
and placebo was not apparent until after 18 months. With Avandia, the cardiovascular safety data emerged only after both the
company and a private investigator examined a very large number of clinical trials in different meta-analyses—nearly eight
years after the drug was first approved.
Doctors learn about these drugs' risks as the research unfolded. However, when it comes to patients, the pharma industry has
done a poor job of explaining risk—and, particularly, unqualified risk. As more safety signals arise from the increasing number
of safety and postmarketing studies conducted, we will need to give patients a better framework for processing the news about
risk. There will be some hard questions to answer. For example, how do we tell the public "there may be something bad happening,
but we aren't sure" in a way that won't cause panic? Regardless, we must begin moving forward. Here are some ideas to get
the industry started.
Accutane. Thalomid. Tysabri. These are the drugs we associate with risk-management plans (RiskMAPs). But actually, many more
drugs have risk-management plans, and many drugs without formal RiskMAPs use some risk-communication tools like "Dear Doctor"
letters, patient package inserts, medication guides, and informed-consent sheets.
These materials must follow the law and provide a message that is consistent with the approved package insert. So, too, must
other marketing communications, which can include anything from DTC ads to detail pieces. However, even though all communications
are based on FDA-approved labeling, they are often at odds with each other. The format, layout, and even the takeaways from
these materials are likely to be quite different—and confusing for patients. As is often the case, consumers get the story
on benefit, and then the story on risk, but no real way to piece these bits of information together.
For physicians who have dealt with package inserts and product promotion for years, such a mixture of messages is not only
tolerated, but also expected. Doctors know that drug company attorneys insist that companies include every possibility. Doctors
also know to take marketing messages with a grain (or, more likely, a pound) of salt and to rely on independent sources of
information, such as academic investigators and medical journals. They are accustomed to scanning these resources, speaking
with reps, and forming their own opinions.