Let's say we can demonstrate that a drug improves patients' functioning, social interactions, and physical well-being. How do we now add sufficient meaning to these outcomes so that physicians in FDA or on its advisory committees can place those benefits into a perspective that will balance the perceived negative physical impact of severe adverse effects?

Benefit and Risk Quantification

Efficacy measures are not directly comparable to efficacy outcomes. Thus, R/B analyses are usually subjective exercises. Data on the disease burden, benchmarking against other drugs, or measuring the quality-of-life impact of the drug (both positive and negative) may help provide a perspective when interpreting risks or benefits. While some have argued in favor of putting all benefits and all risks into a single equation—using metrics such as health utilities or quality-adjusted life years (QUALYs)—these analyses are likely to be too broad and insensitive to be informative because too much information is lost in translating drug benefits and risks into one directly comparable metric.

To quantify pharmaceutical benefits and risks, it will be important to link both positive medical outcomes (such as lower blood pressure or lowered cholesterol) and side effects to intermediate values of importance to patients. For example, even though patients may not feel the benefits of a blood pressure treatment, they know (or they should know) that lowering blood pressure is in their best interest. They also know that experienced or possible future side effects can be harmful or difficult to bear. Understanding how patients appraise and evaluate these positive and negative outcomes—in other words, how they view risk and benefit—will become important.

Benefit and risk quantification will require a better understanding of how physicians and patients make decisions about using medications. Marketing research techniques, such as conjoint analyses, can help to identify how factors are weighted, and decision-analysis techniques may be used to understand how these factors are combined to select an appropriate course of action. New insights into the holy grail of patient compliance, redefined as patient decision-making over time, may provide a new understanding of how to improve drug utilization—a serendipitous outcome of this new research.

Benefit Augmentation

Traditionally, drug companies have added benefits to their drugs by discovering new uses or developing new dosage forms. This clearly increases the real value of new products, and it will continue. But the industry will also need to build value or perceived benefits by understanding to an even greater extent how a drug affects a patient's lifestyle. Again, manufacturers will need to turn to market research techniques—such as ethnographic observations coupled with studies that measure beliefs, emotional reactions/adjustments, and values.

Quality-of-life scales may be highly valuable. But we will likely need more sensitive and customized studies that provide precise measures of how the drug (rather than the disease) affects the patient. For labeling or promotional purposes, FDA requires that such scales have pristine psychometric qualities. It is unclear how well-validated such customized scales will need to be to augment the perceived benefit of the product. Companies will need to better understand how the information they collect will be used in order to plan a program of research.

Because regulatory R/B analyses may be conducted at unpredictable times, it will be important to continuously collect, analyze, and store these benefit analyses in a dossier. Without active project management, we would expect much slippage in time schedules for the completion of such studies. Unlikely outcomes can easily slip down the hierarchy of our to-do list. However, as Nassim Taleb has discussed in his book The Black Swan, it is precisely these highly improbable events that have a massive impact.

Benefit Communication