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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?"
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.
But consumers don't have much experience with combining disparate messages. Drug companies tend to communicate with patients through DTC or risk-communication tools. For mass-market messages and for drugs with mild to moderate risks, DTC can deliver a meaningful benefit message. However, companies marketing drugs with major risk concerns often limit their consumer promotion and, in particular, refrain from broadcast DTC. In both cases, patients don't get the full story.
In the new Culture of Drug Safety, companies will come under greater pressure to increase the flow and usability of information to consumers. Regulators and others will use evaluation oversight (i.e., studies that measure if risk-communication tools are working) to judge if companies' efforts are adequate. These tools will evaluate how patients perceive risk information and how it influences their decisions and behavior. Key to this process for companies will be learning how to package information so that consumers can compare and evaluate benefits and risks, and make a reasoned decision about using a drug.
There are two elements to providing the risk/benefit context. First, the risks need to be fully explained in both relative and absolute terms. For example, for Avandia, we have heard that there is a 43 percent increased risk of having a heart attack. This is based on an "odds-ratio" (a similar index as the relative risk ratio). Patients have not been told about the absolute risk of a heart attack for people taking Avandia (about 6 in 1,000). Nor have they been told that the rate of heart attacks for Avandia patients is similar to the base rate for heart attacks in patients on placebo or other drugs (also about 6 in 1,000).
The second element is "fair balance." Traditionally, FDA and companies have relied on this risk statement to give patients a full understanding of the drug. Clearly, this approach doesn't work. To start with, neither FDA nor drug companies has ever really defined how to achieve fair balance (except, of course, by adding risk information to advertising).
Instead of worrying about what words to provide in a fair balance statement, it may be more important to present patients with a "fair perception" of the drug. This moves the focus off the individual elements of the message (i.e., the current FDA model) and toward understanding the outcomes of risk communication and the ideas about the drug's safety in the patient's mind. This will require companies to really understand how patients learn and comprehend risk. After all, the new safety system shouldn't run on what patients are told—it matters more what they learn and what they do based on that learning.
"Fair perception" can be measured. This can be done in small "copy tests" of the promotional information. Companies that provide prospective patients with draft promotions or risk-communication tools can learn how various materials influence risk and benefit knowledge and attitudes. Some pieces may favor risks to a greater extent than benefits, while other pieces do the opposite. Which perceptions are correct?
If we were to rely on the views of the company, we would select the material that favors benefits; if we were to rely on the views of FDA, we would choose material that favors risks. Instead, the fairest method for judging what's balanced information should come from independent experts—prescribing physicians. After all, they are the ones that must deal with patients' needs as well as the outcomes of a treatment decision.
Of course, one can always argue that physicians can be biased. However, FDA routinely relies on outside experts to form advisory committees, and procedures can be developed to screen physicians for such biases. This group can be further augmented by adding experts in consumer communication and risk management. At the end of the day, the point is that it's important to draw on outside perspectives to gain a better understanding of what is a fair and integrated risk/benefit message.
Would you eat spinach from California? Would you feed your dog pet food from China? Even now, the repercussions of the notifications that those products have a serious risk associated with them persist. The problem isn't only that the media communicated the objective messages of the risk, but that there was a "social amplification" of those risk messages played out in Congress and in reports of regulatory bodies, then communicated repeatedly in the media.
This same type of social amplification has significantly complicated risk communications. Vioxx is a classic case study. After Vioxx was withdrawn, lack of support of the drug safety surveillance system and Congressional inquiries continued to communicate and to amplify the perception of problems associated not only with Vioxx, but with the entire healthcare system.
The public's understanding of Vioxx's risks was greatly influenced by the resultant publicity. Attitudes about the drug, Merck, and FDA were continuously created and updated by processing the press accounts through means both active (e.g., by reading) and passive (e.g., by listening to TV in the background). Because media coverage—not necessarily objective information—drives the amplification of risk, public relations will play a heightened role in the new Culture of Drug Safety.
Companies need to tap PR experts who can draw on more personal communications with patients. This is particularly important when major risks are disclosed and when consumers "reform" their perceptions of a product to integrate the new information. Cognitive psychologists say the information patients have received most recently is more available in memory and is most likely to influence decisions. Therefore, it follows that companies that wish to compete will have to understand what consumers believe and why they believe it—and learn how to balance newly formed beliefs with effective messaging. The new "risk-first DTC" ads for Celebrex are one example of this approach. (See "Risk-First DTC".) Evaluations, whether conducted online, through periodic surveys, or formal RiskMAP reviews of patients' and physicians' beliefs about drug safety, will be increasingly important to influence and maintain a "fair perception" in the minds of prescribers and users.
The advertising and PR industry is always looking for new ways to reach and influence physicians, patients, and the public. Now the pharmaceutical industry, out of necessity, is also looking for new avenues. Expect pharma companies to look to consumer goods (not necessarily consumer agencies) for ideas.
The omnipresence of the Web and the ease of market entrance means medication- or health-related Web sites will continue to grow. Consumers and physicians will gain more control over the content of these sites as they contribute and influence what is communicated online. What some are calling Web 2.0—essentially, community-based participation on the Internet—will evolve rapidly and will significantly change the power relationship in terms of the information supply chain.
Within the pharma industry, the transmission of information has traditionally been "top-down"—that is, from marketers to customers. Expect an increase in "bottom-up" communications. This happens when customers initiate the communication and pharma companies are the passive audience. One example is the recent arrangement between the American Medical Association and Sermo, an online physician-only community. Doctors are free to post any information on the site, but they mostly use it to ask other docs about their treatment experiences.
How can pharma participate in such a bottom-up form of communication, where the audience (in the case of Sermo, physicians) initiates and controls the dialogue? Sermo is still working out the details, however, it appears that pharma will need to adapt to a new role as a information resource for doctors with little ability to control messages and communications. This appears to fit better into the medical-communications and medical-science-liaison "buckets" than classical marketing communications. (Full disclosure: I consult with Sermo and some other companies with innovative communication models.)
Many companies already have huge files of patient names that they gained from databases and mailing lists they purchased or compiled through Internet visitors and redeemers of coupons. They will seek new methods of involving these patients in relationship-building exercises. This will be important, particularly when the safety messages are complicated and evolving. Look for greater use of patients recruited to be "experts" who tell their friends about medicines. If the regulatory challenges can be met (assuring compliance with FDA regulations), such face-to-face communications can be a whole new way to influence people with a condition to see their doctors.
Public relations efforts and events will continue. However, there will be more backlashes, particularly when it comes to obtaining transparent sources of information. The hidden influence of pharma companies in celebrity discussions of drugs, the use of PR firms to draft consumer articles without reference to drug-company funding, and the use of video–press release B-roll—again without reference to source—will continue to come under fire. While OIG has mostly focused its efforts on professional marketing, source-unattributed PR efforts appear vulnerable to investigations and negative publicity as true sources of information are found out and disclosed in the press.
Historically, drug risks have been relegated to informed-consent sheets, package inserts, and fair balance disclosures. While disclosed, the information is often ignored. In the new Culture of Drug Safety, patients will become more in tune with the fact that every drug also has risks. They will expect to receive such information, and they will pay attention to its message.
There will always be various patient segments that differ in how they respond to risk information. Some people will seek to avoid drug risks by ignoring the information, some will delegate all worry to their prescriber, and some will cope by denial. However, the segment of patients that will actively participate in healthcare decision making is growing. The more patients know about drug risks the less they will fear them. They will feel more in control of their own health. Our challenge is to make risk information available in a form that will permit active participation possible. The new Culture of Drug Safety will envelop drug adoption and use. Whether we flourish or flounder in this new culture will be a matter of our adaptability.
This is the last in a three-part series on the new Culture of Drug Safety. Please send comments to firstname.lastname@example.org.