Changing what you can measure: endpoints and stuff

The Avandia (rosiglitazone)story covered at theheart.org and elsewhere, has been portrayed as a big bad pharma versus heroic meta-analysis contest. While GSK has not covered themselves in glory, the FDA conclusion that there is a defensible case for Avandia remaining on the market - but with higher profile warnings and caveats - seems reasonable.
One major casualty is likely to be the reliance in clinical trials of easy to measure surrogate outcomes, in Avandia's case blood glucose. The glitazones are good at controlling blood glucose levels, and that is in part how they captured such a large part of the diabetes market. But it turned out that their effect on clinical outcomes heart attacks and strokes was more equivocal, and in the case of heart failure had an adverse effect.
The use of surrogate endpoints has, in the past, come up trumps. Treatments to reduce high blood pressure and high blood cholesterol, were licensed, marketed and widely used before there was evidence that they had effects on hard clinical outcomes. Lowering blood LDL as a rationale for using statins was controversial in its day. But large scale clinical trials such as the Heart Protection Study later found important clinical benefits too.
It is at least questionable whether the statins would now have been licensed without showing a reduction in hard endpoints such as heart attacks and strokes. That would have witheld their benefits from thousands of people. So a more cautious approach to the evidence on which drugs are approved for use has drawbacks.
There was criticism of the speed at which glitazones began to be prescribed, particularly in north America, without evidence of benefits in clinical outcomes rather than biochemical outcomes. The speed of uptake of statins was much slower, and really only picked up after the first large scale clinical trials showed benefits, initially in higher risk patients and then more widely.
This is perhaps one lesson. We can choose to accept evidence from surrogate outcome studies in licensing drugs if we accept that it is not then appropriate for treatments to be heavily marketed before they have proved themselves in terms of harder clinical endpoints. Or we can decide not to accept surrogate outcomes, and delay the introduction of treatments possibly by many years (and may prevent the development of some treatments altogether).
It's not an easy choice to make. Either way there are risks - from unexpected adverse events, or from the unavailability of possible treatments.