he landscape of clinical research has changed dramatically over recent years. Although many factors have contributed, it should be no surprise that most are related to finances. In 2003, Americans spent approximately $1.5 trillion on their health care, a staggering figure greater than the total gross domestic product of all but five countries in the world.¹ As an important component of the research and development arm of this industry, clinical research is itself a multibillion-dollar enterprise funded by drug and device manufacturers and the federal government. Many sponsors expect a quick return on investment, creating incentives for the rapid and efficient conduct of clinical trials that can be more directly controlled by the sponsor to meet its specific marketing needs.

At the same time, academic medical centers, traditionally the loci of most clinical research, have faced financial challenges that place demands on investigator time and other resources necessary for clinical research, such that many have not been able to meet the needs of research sponsors. Thus clinical research has shifted out of academic centers into private practice, often conducted under the direction of for-profit contract research organizations (CROs) that compete vigorously for research dollars and patients. As in other industries, to reduce costs, clinical research is increasingly being “outsourced” to other countries, a practice that is a logical outgrowth of the profit-oriented mentality that now drives much of clinical research.

As a result, the fundamental relationship between research sponsor and investigator has changed. In the traditional academic center, clinical research was viewed as a collaboration between sponsor and investigator, with the latter having significant input into the design of the study and interpretation of the results. A good example of this process was the discovery of cortisone at Mayo Clinic in the mid-20th century. A Mayo biochemist extracted from the adrenal gland an active component with therapeutic promise. He approached a pharmaceutical company that synthesized enough of the compound to allow a Mayo physician to conduct a successful clinical trial in patients with rheumatic arthritis. Mayo Clinic did not financially profit from this discovery; in that simpler time, before health care became a giant industry, such advances were shared freely for the benefit of others.

In today’s world, the basic discovery process can still occur at an academic center (although it is now equally likely to occur within the sponsor’s laboratory), but the subsequent clinical trials are now likely to be conducted by CROs outside of the academic center. Indeed, because the academic center may stand to reap tremendous financial benefit from its discovery, conduct of a trial to exploit this discovery at the center may pose ethical challenges related to conflicts of interest. Thus, even at academic centers, clinical investigators may provide little intellectual input into trial design and interpretation.

The rapid rise of a clinical trials industry that conducts its work in a mix of academic and private settings has raised several interesting regulatory and ethical issues that are beyond the scope of this article. Rather, what are the implications of these changes for academic anesthesiology?

Many academic centers (including Mayo Clinic) have created their own CROs to take advantage of their considerable experience in the conduct of clinical trials with the goal of generating funds to support academic missions. Others have adjusted their research administrative structures in an attempt to compete successfully as a site for clinical trials. These efforts to fully participate in the new era of sponsored research may have some benefits for departments, as experience is gained with new drugs and devices that may become clinically useful, and faculty members gain familiarity with the clinical research process. In addition, in the past, the funding for such projects was sufficiently generous to provide “leftover” monies for other academic activities. As academic centers are often now just one of many entities competing for sponsored research dollars, however, the opportunities to benefit from such largesse are disappearing. Also, if the academic medical center simply becomes yet another clinical trials site among many, much will be lost. I believe that academic centers have several unique roles to play in the clinical research of the future.

Woody Hayes, the legendary football coach at my alma mater, the Ohio State University, used to say that “you win with people,” and he is right; the investigators who will lead clinical research in the future will not just automatically appear — they must be trained. Clinical research ain’t easy, and adequate training is even more important in today’s complex world. The days when a physician could simply get the check from a sponsor and turn things over to the study nurse are over. In the future, clinical research will increasingly be recognized as requiring a distinctive skill set acquired by specific training and experience and likely documented as part of a credentialing process. The National Institutes of Health (NIH) and others have recognized the importance of a well-trained investigative workforce and have instituted several new programs to train and support clinical researchers, including generous loan forgiveness programs (for details see <http://grants1.nih.gov/grants>). Thus there will likely be numerous career opportunities for good clinical investigators. Unfortunately few anesthesiology departments teach their residents about the clinical research process much less have programs targeted specifically to train clinical researchers. As more clinical research is performed in private practice settings, anesthesiologists outside of academic centers will have the opportunity to participate in clinical research, to the benefit of their practices and their patients. To participate effectively, they need to understand the clinical research process. Such an understanding also will help them to be informed consumers of research information disseminated by pharmaceutical representatives and others with underlying agendas.

NIH has recognized the need for strong clinical research programs that can translate the current wealth of basic discovery into clinical practice. For example, as a part of its “Roadmap” initiative that will guide future policy and funding, NIH envisions the creation of translational research centers that will provide resources and coordination for multicenter clinical research with emphasis on multidisciplinary approaches (see <http://nccam.nih.gov/rtrc>). Academia is a natural home for such centers and other initiatives to construct the multisite research networks necessary to efficiently support the translational research process. To be active participants in such efforts, anesthesiology departments will need to focus on unmet clinical needs of true significance. For example it is hard to argue that the need for a better postoperative antinausea agent is a pressing public health crisis, but problems such as chronic pain certainly are. We have the opportunity to play an important role in efforts to address such issues if we identify and concentrate on what is important.

Finally there will always be a need for independent clinical research driven by motives other than profitable product development. Clinical research that explores the regulation of normal physiology or probes the pathophysiology of disease states is a crucial component of basic biomedical research, and such studies will continue to be pursued largely at academic centers. Academic centers also have an important role to play in the study of new drugs and devices. The aim of most industry-sponsored research is to prove efficacy so that a new technology (a drug or device) may be marketed; these manufacturers are in business to make a profit. However, someone needs to be concerned about how this technology is actually applied to a population. For example a new drug found efficacious in phase III trials may be heavily marketed with a high price tag so that the manufacturer can recoup its considerable investment. Is it in fact sufficiently superior to existing therapies to justify the additional expense? Despite the fact that Americans pay the most for their health care compared with any other country in the world (by far), our health outcomes are actually worse than expected.² The rational application of existing and new health care technologies to populations is a crucial topic for clinical research, one that will become more important as health care cost burdens continue to grow. Considering the investment that society has made in academic health centers, it seems appropriate that this be a focus; if we do not do it, who will?

The huge investments being made by industry and government in biomedical research guarantee that clinical research will continue to be a booming enterprise — as investors demand that findings ultimately be translated to humans. The challenge for academic medical centers is to determine what unique strengths and perspectives they can bring to future clinical research. My opinion is that such strengths are considerable, and that departments who arm themselves with well-trained clinical investigators will be in an excellent position to take advantage of these opportunities.

Reference:

1. Reinhardt UE, Hussey PS, Andersen GF. U.S. health care spending in an international context. Health Affairs. 2004; 23:10-25.

2. Hertzman C. Health and human society. Am Sci. 2001; 89:538-545.

David O. Warner, M.D., is Professor of Anesthesiology and Vice-Chair for Research, Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota.