Clinical Research and its Discontents

The NEJM has published a provocative article about the ethics of the
globalization of clinical trials.  (The article is openly
accessible.)  The big issue is this: clinical trials are very
expensive.  It is cheaper to do them overseas, but this raises
questions of scientific integrity, as well as questions of ethical
integrity.

Ethical
and Scientific Implications of the Globalization of Clinical Research

Economic globalization is an important development of the past half
century. Proponents of globalization highlight the benefits of greater
economic growth and prosperity; critics point to the exacerbation of
economic disparities and the exploitation of workers, particularly in
developing (i.e., low- and middle-income) countries. Pharmaceutical and
device companies have embraced globalization as a core component of
their business models, especially in the realm of clinical trials. This
phenomenon raises important questions about the economics and ethics of
clinical research and the translation of trial results to clinical
practice: Who benefits from the globalization of clinical trials? What
is the potential for exploitation of research subjects? Are trial
results accurate and valid, and can they be extrapolated to other
settings? In this article, we discuss recent trends in and underlying
reasons for the globalization of clinical research, highlight important
scientific and ethical concerns, and propose steps for the
harmonization of international clinical research.

The New York Times has published an href="http://www.nytimes.com/2009/02/19/business/19clinic.html">article
about the article.  In the NYT, they quote an National Institutes
of Health official, who seems dismissive:

Dr. Emanuel of the N.I.H. agreed that it was possible that
some offshore drug research might not be applicable to American
patients. But he faulted the report for seeming to treat all foreign
countries alike. Research conducted in some places outside the United
States -- like Canada and Sweden -- might be perfectly relevant to
American patients, he said.



"It's not a sufficiently nuanced concern to give it credibility," said
Dr. Emanuel.

This is a complex matter.  I'm not sure how nuanced we can expect
a single article (or blog post, for that matter) to be, given the
complexity of the issues involved.  The authors of the NEJM
article conclude:

Conclusions



Long-term solutions to problems arising from the globalization of
clinical research will require input from stakeholders in academia,
industry, and regulatory agencies around the world. The future of the
pharmaceutical and device industries is predicated on addressing these
issues. A comprehensive review including representatives from developed
and developing countries, perhaps commissioned by the Institute of
Medicine or the World Health Organization, is needed to reach
international consensus on these issues. We must ensure the ethical and
scientific integrity of clinical research globally, promote
harmonization of international research, and provide information about
the benefits and risks of new drugs and devices in the populations and
environments in which patients live, wherever they may be.

In other words, the authors' conclusion is that there are serious
questions here.  There are matters that ought to be
discussed.  An appropriate process, in an appropriate forum, must
take place to ensure that ethical and scientific integrity is
maintained.  How is this not credible?  The authors are
posing questions, not casting final judgments.



The authors point out that there are potential benefits to the conduct
of clinical trials overseas.  The drugs under study potentially
will be used in a global population.  Even in the US, the
population is diverse, so it would make sense to include a diversity of
ethnicities and geographic origins in the study population.  Yes,
this does make it more difficult to interpret the outcome of the study,
but that is what statistics are for.  This is not simple, but it
can be done.  As the NEJM article states:

Genetic diversity is often not considered in study design
and interpretation and in the reporting of trial results.

That is true, but is does not have to be that way.  Of course, I
should add, that if one includes these factors in the study design and
reporting, it will increase the cost of the research.  This could
potentially offset some of the savings, but it could add value,
too. 



Of greater concern is the potential ethical implications.  From
the NEJM:

The Declaration of Helsinki expresses an expectation that
every patient enrolled in a clinical trial should, at the end of the
trial, be assured access to the best proven therapy identified in the
study. The reality is that the overwhelming majority of drugs for the
treatment of common diseases are sold in the wealthiest countries.
Therefore, we need to confirm whether the growth in clinical trials
worldwide is accompanied by greater availability of drugs in the
countries where the trials are conducted.

Of course, if the drugs are brought to market, and are proved to be
safe and effective over time, then they eventually will become
available in generic form.  This does not always translate into
affordability, but often it does.  In any case, it takes an
awfully long time.  Does the time course affect the ethical
equation?  And if, as the authors state, "we need to confirm
whether the growth in clinical trials worldwide is
accompanied by greater availability of drugs in the countries where the
trials are conducted," then who is responsible for confirming
this?  What are the consequences if it does not happen?  Does
anyone seriously think that the companies will have to face
consequences for the actions, if they do not deliver on their promises
in twenty years?