Net clinical benefit

We calculate net clinical benefit (NCB) trade-off metric for each benefit criterion against each risk criterion for the purpose of directly comparing benefits and risks. Because the decision-maker's relative importance between benefit and risk criteria are unknown, we estimated NCB over a range of k values. In this setting, k is the scaling factor such that "benefit"=k×"risk" , that is, how much more important is the benefit when compared to risk.

The net clinical benefit of NEPP for benefit criterion i and risk criterion j is calculated as

The NCB for PIN-ER-t are calculated in the same way:

We present in Figure 1 below the results for achieving 10% weight loss versus anxiety as an illustration of the method. The net clinical benefit is plotted against the relative importance of benefit to risk where the larger relative values refer to putting more weight on risks. This is equivalent to saying that a decision-maker prefers to avoid the risk more than gaining the benefit. The benefit-risk balance is achieved when NCB equals zero that is when benefit equals risk. The green area shows the likely NCB values when rimonabant can be considered as a better option compared to placebo based on the two outcomes; and conversely the orange area shows the likely NCB values when placebo would be the better option.

Figure 1The total number of people in the population whose weight loss were attributable to rimonabantafter the number of people who experienced anxiety as a result of taking rimonabant over one year had been discounted (NCB of PIN-ER-1)

For example in Figure 1, when achieving 10% weight loss is valued twice as important than avoiding anxiety (or similarly prefer avoiding anxiety half as much as achieving 10% weight loss) i.e. relative importance of 0.5, the median net clinical benefit is 1,394,850 (95% CI 1,061,146 – 1,725,683) persons over one year (PIN-ER-1). This means that under this model, rimonabant could benefit about 1.4 million people in the population. When weight loss is valued as important as avoiding anxiety, the median NCB drops to 1,168,334 (95% CI 770,077 – 1,523,182) persons over one year. On the other hand, if it is in the utmost interest to avoid anxiety, say with an extreme relative importance of 10, the median NCB drops to –3,027,001(95% CI -5,192,928 – -1,136,701) persons per year suggesting that rimonabant should be avoided. The benefit-risk balance of rimonabant in this situation reverses, NCB<0, when the relative importance of benefit to risk is between 3.4 and 3.5.