Is there a crisis looming in clinical research?
From the May ACP Observer, copyright © 2005 by the American College of Physicians.
By Deborah Gesensway
Timothy G. Ferris, ACP Member, has pulled back from the brink of leaving clinical research more than once.
A clinical researcher at Massachusetts General Hospital and assistant professor of medicine and pediatrics at Harvard Medical School, Dr. Ferris' decade-long career has included a prestigious appointment, competitive grants and dozens of articles in publications from The New England Journal of Medicine to Pediatrics.
But those achievements may not be enough. Now 43 and raising three children, Dr. Ferris is finding that a grueling schedule and pressure to cover 80% of his salary with outside grant funding is draining his energy and enthusiasm. Despite what he called "strong departmental support and terrific mentorship," it is becoming less likely that he will finish his career where he started it: in academia, doing only clinical research.
"I give it a 50-50 shot now," he said. "I was just considering stopping research when I got my RO1" from the Agency for Healthcare Research and Quality last year. The RO1, officially called the research project grant, is the primary grant sought by young clinical researchers who want to establish themselves as principal investigators. Because the RO1 is the grant valued most by medical schools when it comes to tenure and promotions, it could boost Dr. Ferris' career as a health services researcher. Even so, he is not sure this one grant will keep him in clinical research.
"The problem is that when you add up the costs—financial and personal—you have to be really committed to stick with a research career," said Dr. Ferris, whose $1.5 million RO1 will cover 25% of his salary for three years and fund his research into the value of computerized clinical support systems. "With no growth in the National Institutes of Health (NIH) budget, there is going to be even more pressure on junior investigators because there will be less money available."
Faced with these types of issues, a seemingly growing number of clinical researchers are leaving their jobs, either to work in industry or to do full-time clinical care or become hospital administrators. Observers now worry about the high rate of attrition among younger investigators—and the reduced number of medical graduates choosing a clinical research career.
A leaky pipeline
At just the time when there is growing demand for experts who can translate scientific breakthroughs into tools and strategies to improve patient care, the ability to recruit and retain clinical researchers appears to be faltering.
"This is a huge problem," said Milton Packer, MD, professor and director of the Center for Biostatistics and Clinical Science at the University of Texas Southwestern Medical Center in Dallas. "We have done a wonderful job developing the careers of basic science researchers for the last 30 years. Medical schools have invested millions—maybe billions—of dollars in developing career pathways for these individuals and developed recruitment packages to retain competitive faculty."
But that kind of pathway development, he added, hasn't happened for clinical researchers. In fact, he said, their experience may be just the reverse: "They are expected to make it on their own."
That trend may become even tougher as the growth in NIH funding continues to slow. NIH research awards more than doubled from $7.1 billion in fiscal year 1992 to $16.8 billion in 2002, the year that funding for clinical research accounted for 37% of total extramural research dollars. According to an article in the March 12, 2003, Journal of the American Medical Association, not only does support for basic research "far outstrip the commitment to clinical research at the NIH," but clinical research proposals tend to get funded at "roughly half" the rate "of basic science proposals."
The result is what many leaders in academic medicine and scientific research have termed a "crisis" in clinical research. From the NIH (with its 2002 "NIH Roadmap") to the Association of American Medical Colleges (AAMC), experts are now focusing more attention on the problem.
The most recent attempt to identify ways to fix the leaky pipeline of clinical researchers comes from a new AAMC task force on clinical research, which had its first meeting in late February and expects to issue a report next year. At that session, medical school and research deans, professors, and chief executive officers of teaching hospitals gathered in Washington to lay out a plan to study what academic medical centers can do to improve the education, recruitment and retention of clinical researchers. (The AAMC's Web site has more information about its task force.)
"In the old days, before managed care, clinical departments had surplus dollars that they put into the growth of clinical researchers, and now those dollars are gone," said Howard Dickler, MD, AAMC's senior consultant in the division of biomedical and health sciences research and staff representative to the task force. "So the question is, what is to replace it?"
Health care workforce experts worry that not only are too few young physicians choosing careers in clinical research, but that those who do aren't being adequately supported.
Although few studies provide solid data about recruitment and retention, anecdotal evidence provides some consensus. A survey of department chairs and senior research administrators at medical schools published in the Aug. 15, 2001, Journal of the American Medical Association (JAMA), for example, found that 81% of those responding reported that "the challenges facing clinical research in academic health centers [were] urgent or extremely urgent."
Three-quarters of those surveyed complained of a "moderate to large problem recruiting trained clinical researchers." And nine out of 10 reported another "moderate to large problem": pressure on researchers to see patients and generate clinical revenue.
Even faculty on research tracks in many internal medicine departments are required to spend several half-days a week seeing patients or several months a year on consult or medicine services. For some, including Louis H. Griffel, ACP Member, long stints on general medicine service were what convinced him to leave academia nearly three years ago to work at a pharmaceutical company. (See "For some in academia, the drug industry offers a welcome alternative.")
In addition to time-consuming patient care demands, clinical researchers must overcome other barriers. Even as they are expected to bring in money to cover their own salaries and expenses—by winning grants and billing patients—doing the nitty-gritty work of clinical investigation has become more complicated and expensive.
Regulations designed to improve patient safety and privacy are more complex than ever before, and dealing with institutional review boards (IRBs), administrators and lawyers responsible for compliance with the federal Health Insurance Portability and Accountability Act of 1996 (HIPAA) takes time and effort.
And while much attention has been paid to the problems junior researchers face, senior clinical investigators face the pressure of bringing in money to support not just themselves, but entire projects.
"My research team includes 15 people who depend upon us getting the next grant," explained cancer researcher Katrina Armstrong, ACP Member, assistant professor of medicine and epidemiology at the University of Pennsylvania School of Medicine in Philadelphia. "Academic medical centers have traditionally not had clear visions of how to retain and reward clinical researchers."
Another hurdle involves promotion and tenure, with existing policies and procedures slow to change at many universities and medical schools.
"The incentives are structured for researchers to work solo," Dr. Armstrong said. "My promotion and my rewards are based on my work being completely independent." Paradoxically, the research she loves the most—and which has the greatest potential for improving patient health—requires a large multidisciplinary team.
"A real problem in the way a lot of academic places still work is that only the first and last authors on a paper matter," said David G. Nathan, MD, president emeritus of the Dana-Farber Cancer Institute in Boston, professor at Harvard Medical School and author of numerous leading papers on challenges facing the clinical research enterprise. This "author position albatross," as he calls it, holds back many promising clinical researchers back.
Support may be lacking
Another way academic medical centers discourage clinical investigators, Dr. Nathan and other experts argue, is by failing to provide the types of infrastructure clinical researchers need, such as professional statisticians or cutting-edge information technology.
Those needs were a major reason why general internist Douglas K. Owens, ACP Member, chose in 1991 to work at the VA Palo Alto Health Care System in Palo Alto, Calif., when he finished his training at Stanford University: It provided that kind of infrastructure while other places did not. Key to that support, which allows him to do the kind of cost-effectiveness and guideline research he finds incredibly satisfying, he said, are "sufficient time and good mentorship."
"The research career development award program at the VA is noteworthy and outstanding," he said. "The program provides both salary support for investigators and a structured mentoring experience."
A shortage of mentors in the system means that some medical students and residents don't get introduced to the concept of clinical research as a career.
Experts agree with Dr. Owens that mentors are critical. A shortage of adequate role models and mentors means that some medical students and residents don't even get introduced to the concept of clinical research as a career. It also means that young investigators may be left to flounder alone until they swim—or sink.
Confounding this problem is the fact that subspecialists in California, according to Dr. Owens, can "often make two times or more in salary in the 'real world' than they do in academic medicine. That's a big issue, especially when you come out of medical school with great indebtedness." And many mid-career clinical investigators have neither the time nor stability in their own careers to make mentoring others a priority.
"Institutions have to make an investment to encourage mentors to be mentors," said Dallas' Dr. Packer. "We see that [established clinical investigators] are not doing mentoring because they are busy maintaining their own clinical identities. It's a real problem."
New grants enough?
To give budding researchers more support, the NIH five years ago introduced a new grant—the K24—to support clinical investigators at mid-career (associates or those recently promoted to full professorships) so they could spend more time mentoring younger colleagues. NIH officials found, however, that they couldn't give all the money away. (In the first year of the award, NIH gave out 81 K24 grants, and this year-the fifth year of the program—they are funding 259. They have funding for about 400.)
Walter Schaffer, PhD, the NIH's senior adviser for extramural researcher, speculated that those results are due to several factors. For one, he said, clinical researchers are exiting the profession early. In addition, they must spend their time applying for more lucrative and prestigious RO1 grants.
Despite less-than-stellar results, most researchers say the K24 grant and several other relatively new K grant projects from the NIH are helping maintain the clinical research workforce. The largest is called the K23, which gives five years of funding to clinical researchers just embarking on their careers. (Harvard's Dr. Ferris reported that he is also applying for a K23.) In 2004, the program's fifth year, the NIH awarded nearly 1,000 K23s, Dr. Schaffer said, up from 142 in 1999, the first year.
While many in the research community commend the NIH for the K awards, they worry about the ability of clinical investigators to make the jump from K awards to RO1s. They also point out that the success rate of physician first-time applicants for NIH research grants (largely RO1s) still lags behind that of applicants with PhDs, according to a Nov. 6, 2003, New England Journal of Medicine article co-authored by Dr. Nathan.
And they point to concerns about RO1 rules, which generally require that there be only one principal investigator on a grant when the very nature of much modern clinical research requires teams of investigators.
At the same time, clinical researchers point to encouraging signs that medical schools and teaching hospitals are starting to provide the kind of institutional help clinical researchers need.
At Massachusetts General, for instance, Dr. Ferris said there is now a wide range of support including mentorship, educational opportunities, IRB assistance, free statistics support and grant review. In addition, the hospital is investing in its clinical researchers by giving them seed money to fund pilot research projects.
And Philadelphia's Dr. Armstrong noted that the University of Pennsylvania Medical School has embarked on an ambitious agenda to redesign incentives to nurture clinical and multidisciplinary research. That agenda includes novel training programs to provide the skills necessary for clinical research as well as examining the need to change the traditional criteria for tenure-track researchers.
According to Dr. Armstrong, multidisciplinary research projects are the future of clinical research, not only because of their "potentially very high impact in terms of improving people's health," but also because they keep investigators interested in and committed to their careers. They offer a place for junior investigators to be involved, but also keep more senior researchers from burning out.
"What's critical for faculty is to get frequently reminded why they are doing the research they are doing," she said. "It's important to step back from filling out forms and IRB applications that you forget to sit back and say, 'I'm doing this because I just saw a patient who could die because we haven't done this research.' I'm not sure how you keep that in your blood—but I think it's critical."
Deborah Gesensway is a freelance health care writer in Toronto.
Sometimes, the driving force is more money. Sometimes, it is more stability and work-family balance. Other times, it's escaping academic politics or policies.
Whatever prompts the move, academic medicine's loss is sometimes a drug company's gain.
Research experts say that in general, there are no hard feelings when an academic jumps ship to industry, largely because both arenas share some common goals.
"The pharmaceutical companies are part of the process," explained Howard Dickler, MD, senior consultant with the division of biomedical and health sciences research at the Association of American Medical Colleges. "We need people who know what they are doing in pharmaceutical companies if we are going to get new treatments."
As one sign of the somewhat symbiotic relationship between academia and industry, the National Institutes of Health's "Roadmap" for re-engineering the clinical research enterprise calls for even greater cooperation between academia and industry.
When he decided to leave his assistant professor post at Robert Wood Johnson Medical School in New Brunswick, N.J., gastroenterologist Louis H. Griffel, ACP Member, was fleeing the frustration of too much clinical work, as well as too little money, nursing and lab support to make much progress on his research into Barrett's esophagus and hepatitis C.
Only later did he realize that he was not just running away from one career, but moving toward something new. Now at Schering-Plough Research Institute in Kenilworth, N.J., after a brief stop at Purdue Pharma in Stamford, Conn., he gets to work directly in the institute's primary area of clinical interest: drugs related to hepatitis C.
While the move has boosted his salary, he said it's also afforded him "a better lifestyle, a more pleasant work environment, better hours and interesting work. I am not in a position to save a person's life these days, but if I work hard over the next four or five years, I could potentially save thousands of patients' lives."
Margaret Burroughs, MD, also left an academic clinical research career a few years ago for a position in the pharmaceutical industry. Like Dr. Griffel, she said she didn't realize how little she would miss academic medicine. "I don't regret the decision one bit," she said firmly.
While at Mt. Sinai School of Medicine in New York, Dr. Burroughs had come to the conclusion that there was no way to accomplish the kind of research she was interested in doing. The problem? The growing amount of clinical care demanded by department chairs and hospital administrators.
Successful clinical researchers in academia now have to be as entrepreneurial and business-savvy as their colleagues in private clinical practice.
Between 1994, when she arrived at Mt. Sinai, and 2002, when she left to become a clinical project director at Schering-Plough, she said she realized that successful clinical researchers in academia now have to be as entrepreneurial and business-savvy as their colleagues in private clinical practice.
"It used to be that to be successful in an academic medicine setting, you just had to be smart," she said. "Now you need to be an entrepreneur too. It really changed since the beginning of my career to now."
When people talk about clinical research, they are referring to several very different kinds of patient-centered studies. It should be no surprise, then, that the challenges encountered by physicians in each type of research require different solutions, explained William F. Crowley Jr., MD, director of clinical research at Boston's Massachusetts General Hospital.
His article in the March 3, 2004, Journal of the American Medical Association proposed a major overhaul of the country's clinical research infrastructure, which he called "fragmented, outdated and ailing," and generally not up to the task of "transferring novel basic research into improved patient care."
Here's an overview of how he defines different types of research—and the challenges that each faces.
Translational research. This field refers to studying both how to bring discoveries made in the laboratory to play in patient care, what is often referred to as "bench to bedside," and the increasingly common reverse of that process, in which the study of patients and families with genetic disorders leads to the discovery of new genes, pathways and drug targets.
These are the kinds of research that really can be done only at academic health centers, because that is where the patients, clinicians and bench scientists all converge. These days, some of the most exciting translational research focuses on using the tools of the human genome project to understand how to treat patients with specific diseases.
"This is the kind of clinical research most difficult to sustain a career in over a full career," Dr. Crowley said. "It is completely dependent on NIH funding, it requires partnerships with basic scientists and there is an increasing regulatory burden" of complying with human subject protection rules.
New drugs and procedures. A much larger group of clinical researchers, he said, conduct interventional clinical trials of new drugs and procedures, much of which is funded by pharmaceutical, device and biotechnology companies. There is a whole continuum of clinical trials, from those run completely by academicians, which is rare, to work-for-hire for pharmaceutical companies, which is more common.
Because many of these projects are dependent on industry funding, Dr. Crowley said researchers are often subject to "funding unpredictability."
Health services research. This type of clinical research—which Dr. Crowley characterized as in "ascendancy"—focuses on outcomes and effectiveness studies. Funding often comes from third-party payers or other organizations involved in outcomes, disease management and health services research. One problem is that researchers often don't have adequate training in the skills they need to do these studies, from biostatistics to public health.
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