Jim Gearhart

by Jim Gearhart

A Novel Addresses Clinical Research: How Factual is the Fiction?

Even though fiction often sensationalizes medical research, I still enjoy finding references to it in a movie or a book. This happened the other day with John Grisham’s 2011 novel The Litigators. I like Grisham’s books, especially his descriptions and the dramatic legal situations he creates, and The Litigators was no exception. The interest-piquing nod to clinical research came when the story’s protagonist cross examines the vice president of a large pharmaceutical company. The topic was the development of the company’s controversial drug, Krayox. I perked up even more when the beleaguered pharmaceutical executive admitted that not one of the company’s drug studies happened in the United States.

 

I can appreciate the value of creative license, when an author seeks to increase tension or emotion. And Grisham, clearly, is a talented writer. But a danger in novels is that readers may lump fictional flourishes in with the facts, and come away with an erroneous impression. With that in mind, I wondered, how likely was it, really, that the FDA would approve a drug without any research in the United States?

Pull-Quote-1

From what I found in the regulations and data, it seems possible, but not likely. The FDA clearly is willing to accept data from research overseas; the agency updated its regulatory guidance in 2012, and a section of FDA regulations addresses specifically requirements for research done completely overseas. Key to accepting the results is that the research was done to international standards and conducted by credible researchers.

Pill ImagesFor years, industry observers have watched closely the expansion of research overseas.  In 2001, pharmaceutical company Merck said it was conducting 35 percent of its research overseas. A New England Journal of Medicine article in 2009 found that a majority of late-phase research was conducted overseas. The article reported that in 2006 four out of ten investigators registered with the FDA worked outside of the United States. That was a fifteen percent increase from four years before. Even with those numbers, though, and the regulations, would the FDA accept one hundred percent of a company’s research from outside the United States?

The NEJM article gathered some of its information from clinicaltrials.gov, a federal database for tracking medical research. So I went there to see how things looked in 2014, five years after the NEJM article was published. Researchers must post on Clinicaltrials.gov all studies that operate under FDA regulations, including research that companies hope to use when requesting a drug’s approval.

I ran searches for industry-sponsored Phase III research (I limited it to Phase III because the NEJM article did, too). I then divided the results into three groups: Studies operating in the United States and abroad; studies happening only abroad, and studies happening only in the United States. Here’s the breakdown of Phase III studies that, according to clinicaltrials.gov, were recruiting subjects on that day:

Location of Phase 3 Studies: US vs. Overseas

Table of Phase 3 Study Locations

The significance of “overseas only” surprised me. Almost half of the protocols listed in clnicaltrials.gov were exclusively overseas. (Even more surprising was that only a handful of studies are underway only in the United States). It truly is a time of global medical research. But, looking closer at the “Overseas Only” studies, most if not all also had related protocols underway (or completed, or planned) in the United States. But overall, the sworn testimony of John Grisham’s fictitious pharmaceutical executive ended up more plausible than I expected.

Debate continues whether increasing overseas research is desirable or not. The 2009 NEJM article summarized well some of the practical and ethical issues that arise, such as cost-savings for research in a particular country versus availability of the drug in that country after approval; wider availability of eligible study subjects in the population versus varying standards of health care; and acceptable study designs versus local regulations or ethical guidance.  These are the issues that we as researchers, ethicists, and sponsors should pay close attention to, beyond the pages of the latest legal thriller.

Debate continues whether increasing overseas research is desirable or not. The 2009 NEJM article summarized well some of the practical and ethical issues that arise, such as cost-savings for research in a particular country versus availability of the drug in that country after approval; wider availability of eligible study subjects in the population versus varying standards of health care; and acceptable study designs versus local regulations or ethical guidance.  These are the issues that we as researchers, ethicists, and sponsors should pay close attention to, beyond the pages of the latest legal thriller.

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