August 17, 2015
Growing Input-Outcome Disparity In Biomedical Research

Computers, a many orders of magnitude decline in DNA sequencing costs, big advances in knowledge of how genes, cells, and organisms function, and the growth in microfluidics technology have not increased the rate at which new therapies come to market.

The general public funds the vast majority of biomedical research and is also the major intended beneficiary of biomedical breakthroughs. We show that increasing research investments, resulting in an increasing knowledge base, have not yielded comparative gains in certain health outcomes over the last five decades. We demonstrate that monitoring scientific inputs, outputs, and outcomes can be used to estimate the productivity of the biomedical research enterprise and may be useful in assessing future reforms and policy changes. A wide variety of negative pressures on the scientific enterprise may be contributing to a relative slowing of biomedical therapeutic innovation. Slowed biomedical research outcomes have the potential to undermine confidence in science, with widespread implications for research funding and public health.

This is a problem.

Society makes substantial investments in biomedical research, searching for ways to better human health. The product of this research is principally information published in scientific journals. Continued investment in science relies on society’s confidence in the accuracy, honesty, and utility of research results. A recent focus on productivity has dominated the competitive evaluation of scientists, creating incentives to maximize publication numbers, citation counts, and publications in high-impact journals. Some studies have also suggested a decreasing quality in the published literature. The efficiency of society’s investments in biomedical research, in terms of improved health outcomes, has not been studied. We show that biomedical research outcomes over the last five decades, as estimated by both life expectancy and New Molecular Entities approved by the Food and Drug Administration, have remained relatively constant despite rising resource inputs and scientific knowledge. Research investments by the National Institutes of Health over this time correlate with publication and author numbers but not with the numerical development of novel therapeutics. We consider several possibilities for the growing input-outcome disparity including the prior elimination of easier research questions, increasing specialization, overreliance on reductionism, a disproportionate emphasis on scientific outputs, and other negative pressures on the scientific enterprise. Monitoring the efficiency of research investments in producing positive societal outcomes may be a useful mechanism for weighing the efficacy of reforms to the scientific enterprise. Understanding the causes of the increasing input-outcome disparity in biomedical research may improve society’s confidence in science and provide support for growing future research investments.

If US FDA and NIH policies are a large part of the problem then that is very unfortunate. They are not likely to change, especially not the FDA.

Why does this matter? Our lives depend on the rate of advance of biomedical treatments. We all have an expiration date on our bodies absent some really big advances in methods to rejuvenate aging bodies. How many decades do you have left to live? Not as many as you would have if only increased spending on biomedical research had translated into a more rapid rate of progress in the development of gene therapies, cell therapies, and other therapies needed for tissue repair and rejuvenation.

Update: The US FDA errs far too much on side of avoiding approval of a bad drug and as a consequence it blocks development of good drugs.

Share |      Randall Parker, 2015 August 17 10:21 PM 

bob sykes said at August 18, 2015 5:31 AM:

The big advances in health were made in the 19th Century, and those were specifically improvements in public sanitation (sewerage and treated water supply, especially chlorination ca WW I), greatly improved agricultural productivity (virtually all famines in the last 150 years, including the Irish famine, were political choices) and greatly improved transportation. The latter allowed fresh food deliveries year round. Within the 20th Century, the biggest improvement was refrigeration, which allowed food storage and long range transport, and food production regulations that eliminated food contamination.

The chief contribution of medicine was antibiotics. Prior to WW II doctors essentially provided first aid, and hospitals were death traps. Even today, doctor error in hospitals kills about 90,000 people a year. This is 50% higher than the number of deaths due to auto accidents and gun shots. Many of the medical deaths can be attributed to simple sanitary technique failures--people, wash your hands.

It is not surprising basic research provides so little benefit; it's not supposed to. The biggest problems with applied medical research are incompetent and corrupt researchers. The bulk of medical research is unreproducilble, and the published data often does not support the claims being made because of bad experimental desigh and incompetent statistical analysis.

Nick G said at August 18, 2015 9:26 AM:

Randall, you heretic! You want to actually cure disease and reduce suffering. Don't you realize that's not the purpose of drug research??

New drugs are produced by drug companies. Drug companies don't want to increase the rate of innovation: they want the minumum level of innovation that will fill their new product pipeline. Any greater level of innovation would produce benefits for consumers, but not for drug companies, and would potentially shutoff the pipeline eventually.

Drug companies (and doctors in general) don't want to cure anything at all: they want to convert acute illness into chronic illness, treated by expensive daily drug regimens.

Parker Bohn said at August 26, 2015 1:34 PM:

This is the case with science in general: its getting cumulatively more difficult to produce meaningful advances.

Luckily, we've greatly expanded the number of scientists and researchers --- there are millions and millions of them worldwide (how many scientists of any kind were there in the year 1000 AD?).

Even in fields like pure mathematics it takes more and more effort to accomplish anything. Compare early proofs such as the infinity of prime numbers, or the Pythagorean Theorem, to the 4-color map proof, which is so long and complicated that it takes a computer to verify.

Merovign said at August 26, 2015 3:46 PM:

My conclusion, after trying to deal with a large number of trials over the last several years as a potential recipient of therapy, is that the goal of most research is not treatment, it is more research.

Even if the results of the trial are significantly positive, they are primarily used to justify more grants and funding rather than conversion to therapy. That's why effectively the same trial is done over and over and over again.

Most of what I've been following has been in cardiology, but also metabolic and stem cell research in general seem to follow this pattern pretty closely.

Nick G said at September 3, 2015 1:08 PM:


I think you're talking about essentially the same problem that I was discussing, which can be generally called "careerism". This is a problem in many areas. For instance, penal systems don't want to eliminate recividism, because that would cost jobs. They'll never, ever admit it, but it's the truth.

Medical researchers don't want to produce anything at all, but especially not a definitive result that will close off their research.

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