The Impact of New (Orphan) Drug Approvals on Premature Mortality from Rare Diseases in the U.S. and France, 1999–2007

This paper investigates the impact of the introduction of new orphan drugs on premature mortality from rare diseases using longitudinal, disease-level data obtained from a number of major databases. The analysis is performed using data from two countries: the U.S. (during the period 1999-2006) and France (during the period 2000-2007). For both countries, we estimate models using two alternative definitions of premature mortality, several alternative criteria for inclusion in the set of rare diseases, and several values of the potential lag between new drug approvals and premature mortality reduction.

Both the U.S. and French estimates indicate that, overall, premature mortality from rare diseases is unrelated to the cumulative number of drugs approved 0-2 years earlier, but is significantly inversely related to the cumulative number of drugs approved 3-4 years earlier. This delay is not surprising, since most patients probably don’t have access to a drug until several years after it has been launched. Although the estimates for the two countries are qualitatively similar, the estimated magnitudes of the U.S. coefficients are about four times as large as the magnitudes of the French coefficients. This may be partly due to greater errors in measuring dates of drug introduction in France.

Our estimates indicate that, in the U.S., potential years of life lost to rare diseases before age 65 (PYLL65) declined at an average annual rate of 3.3%, and that, in the absence of lagged new drug approvals, PYLL65 would have increased at a rate of 0.9%. Since the U.S. population age 0-64 was increasing at the rate of 1.0% per year, this means that PYLL65 per person under 65 would have remained approximately constant. The reduction in the U.S. growth rate of PYLL65 attributable to lagged new drug approvals was 4.2%.

In France, PYLL65 declined at an average annual rate of 1.8%. The estimates imply that, in the absence of lagged new drug approvals, it would have declined at a rate of 0.6%. The reduction in the French growth rate of PYLL65 attributable to lagged new drug approvals was 1.1%.