"I remember wondering if the pace of innovation from 1950 to 1980, when we only knew a certain amount [about biology], had been faster than the pace of innovation between 1980 and 2010," said Arturo Casadevall, chair of the department of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health. "Thinking of all the things that were found between 1950 and 1980: blood pressure medicines, antibiotics, heart transplants… and that had been learned with only a very limited amount of knowledge compared to what we know now. And I kept thinking, could things be slowing?"
Casadevall and graduate student Anthony Bowen used a pretty straightforward technique to try and answer the question. They compared the NIH budget, adjusted for inflation, with the number of new drugs approved by the Food and Drug Administration and the increases in life expectancy in the U.S. population over the same time period.
Those crude health measures didn't keep pace with the research investment. Funding increased four-fold since 1965, but the number of drugs only doubled. Life expectancy increased steadily, by two months per year.
But Pierre Azoulay, an economist at the Massachusetts Institute of Technology Sloan School of Management who has spent several years trying to answer the same question said that although the study is well-intentioned, it is rife with limitations and assumptions. For example, new drugs or life expectancy improvements will lag the science that lays the foundation for them, often by years or even decades. So examining the NIH budget year by year and comparing it to the number of drug approvals in that same year isn't a good measure of whether the investment is working.
"The question is whether that’s an interesting thing and whether that’s a policy-relevant fact. I would say not," Azoulay said. "I would say it is possible the productivity of biomedical research expenditures has been going down over time. It’s not outside the realm of possibilities, but we’re not going to learn whether this is a fact from this study."
Azoulay pointed out a number of other limitations . Although the researchers adjusted for inflation, they didn't take into account the increased cost of doing research. They didn't look at investment by the private sector. The research team did acknowledge that gains in life expectancy are harder to make when the average lifespan has increased due to previous success. But what this study -- and a handful of others published over the past few years -- may bring to light is not a stark drop in the efficiency of the U.S. federal expenditure on biomedical science, but our stunningly imperfect understanding of how to measure the return on the investment.
"NIH agrees that it is critical to assess whether progress in biomedical research is achieving its ultimately desired outcome – better health for the nation and the world," Francis Collins, the director of the NIH, said in a statement. "That is, however, a challenging task, and previous published economic analyses of the return on investment for NIH-supported research have led to radically different conclusions."
For example, a 2009 study in the same journal that examined research funding over 50 years in separate categories. In four disease areas -- cardiovascular disease, stroke, cancer and diabetes -- as research money flowed in, the mortality rates decreased.
Casadevall and Bowen said in an interview that their data is too premature to shape policy, but both believe it is important for scientists to begin to use the tools of science to understand how to make the best possible investments.
One possible interpretation of their data, Casadevall said, is that it has gotten tougher to make gains in life expectancy or new drugs because the easier diseases have been solved, leaving the trickiest ones -- such as Alzehimer's and Parkinson's -- to be unraveled. That might suggest that more investment will be needed to make progress.
However, the broader question of whether the federal expenditure on research really leads to gains in health is a crucial and sometimes divisive one. Calls for an expansion in funding for biomedical research have become pervasive as scientists find their livelihoods threatened by years of flat funding from the federal government, and they passionately argue that funding cuts will ultimately stall advances in medicine. Some critics believe that the underlying premise -- that more research money means more breakthroughs and better health -- needs to be more scientifically examined.
"I think where we need to start is here," said Daniel Sarewitz, a professor of science and society at Arizona State University. " We’re still in the grip of this silly belief if you pour more money into knowledge creation, you’ll get more benefit. Let’s have a conversation about the kinds of institutions we really need."