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.
Drug benefits are usually looked at from a medical perspective in which physiological outcomes dominate. However, that's more
difficult to do for drugs that treat cosmetic problems (such as hair growth or removal), lifestyle issues (erectile dysfunction
or birth control), or complex conditions whose medical impact is difficult to evaluate (depression or irritable bowel syndrome).
Historically, the National Institute of Mental Health (NIMH) has had a very difficult time convincing the public of the large
negative impact that depression has had on our society. Data from the Medical Outcomes Study that compared the impact of several
diseases, including depression, on quality of life helped to put these issues into perspective. But such benchmarking across
diseases is rare for FDA.
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.
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.