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ALS Worldwide
January 29, 2015

Why Most Clinical Trials Fail

Dr. Peiman Hematti of the University of Wisconsin-Madison, Associate Professor of Medicine, Pediatrics, Surgery, Biomedical Engineering and Director of the Clinical Hematopoietic Cell Processing Laboratory offers his views on this challenging topic.

"The scientific community used to assume that the claims in a research publication could be taken at face value. Unfortunately, it is now becoming clear to the scientific community, pharmaceutical companies, and funding agencies, including the NIH, that we are facing a crisis in translational science and pre-clinical research. Most of the time, the scientific claims in research papers do not stand the test of time. Indeed, the issue of irreproducibility of scientific data is not new and has been the subject of controversy and debate for decades. 

However, the staggering cost of potential new drug development (up to hundreds of millions of dollars), the very high number of late-stage clinical trials that have shown promise in earlier phases but eventually fail, and most importantly, the human costs associated with failure of promising therapies for patients with terminal illnesses have brought more attention to this widespread problem in biomedical research.

This situation is very familiar to patients with ALS and their families. Over the last decade, there have been several large scale and late phase clinical trials based on very promising results in laboratory and preclinical animal research.  There are numerous reasons why clinical trials fail. These include the limitations inherent to in vitro studies; the lack of suitable animal models for a disease; the lack of attention paid to details while designing pre-clinical research, which should always include the best animal models available; not using the right control groups in animal studies; lack of attention to pharmacodynamics and pharmacokinetics of drugs; and incomplete presentation of relevant data including negative results. Unfortunately, there is also a culture of 'publish or perish' in academia that pushes investigators to publish their results, many times incomplete and prematurely, at the cost of not paying attention to details.

Addressing the systemic issue of lack of reproducibility demands the careful attention of investigators, academic centers, pharmaceutical companies, funding agencies and patient organizations.  Research is mostly funded by community taxes (NIH), philanthropy donations or patient advocacy groups, all with the hope that such research can help the life of fellow human beings. It is essential to remember that patients are at the heart of this matter.  At a minimum, a patient's enrollment in one clinical trial means that s/he is mostly excluded from participation in other, potentially promising clinical trials.  Because of this, scientists must be extremely careful with their work in translational research and pre-clinical studies. Every failed clinical trial, rather than being ignored or forgotten, should be carefully and fairly scrutinized so lessons can be learned to avoid repeating the same mistakes. Researchers should realize that any scientific paper can be both a publication in their academic portfolio and the basis of a clinical trial where patient lives are at stake."   

Dr. Hematti's views are beginning to take hold throughout the scientific community.  A recent Nature article by Erika Hayden entitled Misleading Mouse Studies Waste Medical Resources begins with the statement, "A running joke among health researchers is that everything has been cured - in mice!" This is a sign of changing times and awareness that animal trial results can waste the valuable time and energy of participating patients and scientific resources. Changes in direction are clearly taking place for the better.