Monday, August 1, 2011

Helping Patients Assess the Benefits of their Drugs: Reading Inside the Box and Between the Lines on Drug Efficacy

Nothing creates advertising memes faster than DTC promotion – not even Super Bowl commercials – because health professionals and “civilians” alike take prurient interest in the conversation between pharmaceutical companies and patients. It’s not surprising, then, that Rx drug ads are both the inspiration for cultural jokes (can anyone look at a claw-foot bath tub without thinking of erectile dysfunction?) and the launch point for serious public health commentary.

Case in point. In a recent op-ed article in the NY Times, “Think inside the box,” authors, Steven Woloshin and Lisa M. Schwartz, two Dartmouth Medical School professors, urge use of patient Fact Boxes that feature not just drug side effects but also data on efficacy – which, in many cases, turn out to be less impressive than what optimistic patients imagine them to be. The presumption, which seems hard to refute, is that patients can make more educated choices about the risk-benefits of drugs when they know more – not just about the risks, but also about the benefits, or lack thereof.

Clearly, in the modern age of pharmacovigilante-ism, this is a high priority for FDA, which is squirming awkwardly in the space between two stools: the public health benefits that redound when patients take the prescribed drugs they might need but currently avoid taking, and the public health risks averted when patients reject drugs they feel are unsafe. The authors point, as object lesson, to Abilify, a drug slotted as second-line (add-on) antidepressant therapy for patients who, by definition, are difficult to treat, if not refractory. (Full disclosure: the makers of Abilify have never sought my advice on that product and I hold no particular brief for it.)

It’s ingenuous to argue that drug information boxes – terse and sterile, without context or conversation – can do a very good job of conveying efficacy to the lay patient. Drug efficacy has to be viewed amid data and clinical experience available for an entire category of drugs, as well as information regarding drug study design and FDA approval policies. As one who has countless times watched physicians struggle to interpret data put before them in market research, and who has observed striking levels of confusion about drugs unmasked in cocktail conversation with well-educated patients, I despair of relying on a few lines in a drug warning box – simply written or otherwise – to get the job done.

All therapies work idiosyncratically in some patients and not in others – and no market illustrates this better than antidepressant therapy, a market category in which sizeable proportions of patients do not respond to any given drug. In the future, we will have biomarkers to help screen promising patient candidates for certain types of therapies, but for now, we have principally trial and error to guide us. It’s the role of the physician to set and manage patient expectations – even for those patients who can be induced to read drug fact boxes. (Outside of market research settings, many of them can’t.) Indeed, patients with debilitating depression should not be left by themselves to decide whether the odds of success are high enough to warrant a 4-week trial.

Underscoring the point here, the authors represent Abilify’s odds of success as just 10% – the net of test minus placebo control – a calculus that fails to acknowledge the practical conundrum associated with the way we conduct and interpret clinical trials. Without meaning to cast aspersions on experimental design, I hypothesize that placebo-control may actually understate the true benefit of active drugs investigated for mood disorders. It’s medically unethical to give patients placebo in the real world, and no one really knows how to assess the durability of “placebo effects” – the chicanery of mind against body. We can look only at clinical experience with drugs and then make empiric judgments about prospects of success based on what we observe.

I am not about to argue that the dialogue between physicians and patients is always what it should be; nor can I inveigh against the “motherhood” proposition that patients should have access to straightforward information. But I am convinced that improved conversation between patients and physicians is the first and best hope for informed decision-making, and we should not count on telegraphic commentary from FDA to substantially improve it. For other points of view on this debate, please see:

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