The Wall Street Journal points to an extremely successful drug study in the 1980s. Researchers showed they could lower the heart-attack death rate to 8% from 13% by giving patients aspirin and a drug called streptokinase. These days, though, an 8% mortality rate would be disastrous; the rate in most studies of heart attack patients is somewhere around 4%. That points to a challenge for companies developing new therapies for heart disease (and other well-treated maladies). To some extent, drug companies are already shifting their focus to poorly treated forms of cancer and other diseases where it may be easier to improve on existing therapies.

Drugmakers have taken varied approaches to dealing with the innovation dilemma. Some companies have a few strategies for showing improvements in already well-treated populations. These strategies can be useful in developing new therapies, but can also be problematic, argue the authors of the JAMA essay, Drs David Kent and Thomas Trikalinos, both MDs affiliated with Tufts Medical Center, Boston, USA.

One strategy is to shift from measuring a single endpoint – such as death – to measuring a combination of several endpoints. Sometimes, though, these composite endpoints can mask important distinctions. For example, researchers might find that a new therapy improves a composite endpoint that includes death, repeat heart attacks and repeat medical procedures, but a closer analysis might suggest that the therapy actually lowers the risk of repeat procedures but not death or repeat heart attacks.

Another option is to look at so-called surrogate endpoints, changes that are not in themselves clinically significant, but that raise the risk of future events such as heart attacks or death. This has been suggested for research in stents, the authors note. And surrogate measures are already widely used in studies of drugs used to prevent heart attacks – as the controversy over Merck’s cholesterol drugs Zetia and Vytorin shows.

The shift from single endpoints to composite endpoints to surrogate endpoints can be seen as a kind of evolution of a field, as outcomes get better and better, the JAMA authors suggest. They write: “The evolution of assessed outcomes from hard clinical outcomes (i.e. death) to composite outcomes (including softer, less important clinical endpoints) to surrogate outcomes (of possible, but not definite, clinical import) may signal a maturation in technological development toward innovation to extinction”.

References:
Martino M. Biopharma: Innovating to extinction? FiercePharma. 2009 Nov 25.

Goldstein J. Can Drug & Device Makers Innovate Themselves to Extinction? The Wall Street Journal. 2009 Nov 24.

Kent DM, Trikalinos TA. Therapeutic Innovations, Diminishing Returns, and Control Rate Preservation. JAMA. 2009;302(20):2254-6.