Oscar Crofford: On the horns of a revolution
Oscar Crofford and the landmark trial that changed diabetes forever
Editor’s Note: This profile was written in 2003. For an update on Oscar Crofford, see story in June 2008 issue of House Organ
What they may not realize is that the retired Vanderbilt University professor approaches his new passion with the same intensity and humor with which he led a landmark study that established the value of rigorous blood glucose control a decade ago.
“I’ve learned more about labor and delivery and care of the newborn from these cows than I ever did in medical school,” he says with a chuckle, his sky-blue eyes twinkling under a shock of white hair.
The tale of the study, called the Diabetes Control and Complications Trial (DCCT), is worth repeating, for it revolutionized the treatment of the disease. Crofford’s life story is equally compelling, for it illustrates how an adventurous spirit can achieve a breakthrough in understanding that dramatically improves the lives of patients.
Born in Chickasha, Okla., in 1930, Crofford attended high school in Memphis, and after graduation, decided to Vanderbilt. Because of the post-war shortage of physicians, he was able to enroll in an accelerated program, and earned both his bachelor’s and medical degrees in seven years. He and the former Jane Long, a recent Vanderbilt nursing school graduate, married during his residency in 1957.
After a two-year stint as a medical officer in the Navy to fulfill his military obligation, Crofford returned to Vanderbilt for a fellowship in clinical physiology under the late Dr. Elliott V. Newman, a pioneering physician-scientist who established Vanderbilt’s federally funded Clinical Research Center – one of the first in the nation.
Newman “was really one of the first of a new breed of physicians who bridged the gap between clinical medicine and basic science,” Crofford recalls. “He told me, ‘Here’s your lab. Go in there and discover something.’ It was sort of the sink-or-swim philosophy of science.”
Newman also became a trusted advisor and counselor. “He was a wonderful scientist and a wonderful human being,” Crofford said. “I’d say my character and sense of how to work with people I’ve learned mostly from Elliott Newman … I probably modeled my life to a large extent after (him) and the way he treated me.”
Vanderbilt in the early 1960s was brimming with scientific excitement, in large part because of the “brain trust” in metabolism research attracted by the trail-blazing physiology professor Charles “Rollo” Park. “Those were the grandest years ever of medical science,” Crofford maintains. “We were just in the forefront of the technological revolution in medicine, the scientific revolution, things that were never possible in the past … That’s where the excitement was. That’s where the fun was.”
After returning to Nashville in 1965, Crofford became Vanderbilt’s first full-time diabetes specialist. He knew more about insulin action than diabetes care, but fortunately he was able to learn on the job under the direction of the late Dr. Addison B. Scoville Jr., a member of Vanderbilt’s clinical faculty who ran the Vanderbilt diabetes clinic.
“Virtually everything I learned about caring for people with diabetes I learned from ‘Ad’ Scoville,” he says.
Crofford also expanded his administrative skills. He established the Division of Diabetes, and helped bring the nation’s first federally funded diabetes research center to Vanderbilt in 1973.
“The person who sent in the application (to the National Institutes of Health) had to be a physician … so I served as the principal investigator (for the center),” Crofford says. “But it was really capitalizing on work done by … a whole slew of outstanding basic scientists.”
At the time, Scoville was president of the American Diabetes Association, and introduced his protégé to the potential and power of the non-profit organization. Soon Crofford was serving as vice chairman of its research committee, and he was called to Washington, D.C., to testify on behalf of a bill to increase federal funding for diabetes research.
“I had no earthly idea what to do,” he recalls. “I didn’t even know what you called your congressman or senator -- Your Honor, or what?” So Crofford went to the Vanderbilt library, and taught himself the art of testifying by poring over transcripts of previous hearings.
The hearing before Sen. Ted Kennedy’s health subcommittee, and subsequent lobbying by the diabetes community ultimately were successful, and in 1974, President Richard Nixon signed what the ADA describes as the first diabetes law in U.S. history. Among other things, it mandated establishment of a National Commission on Diabetes to formulate a “long-range plan to combat diabetes.”
The report was delivered to Congress in December 1975. “I spent a lot of time as a health lobbyist at that point,” Crofford recalls, trying to get the recommendations implemented.
Crofford and Scoville approached the Tennessee congressional delegation, and convinced every member to support additional diabetes legislation. They took a group photo of the now-unanimous delegation, displayed it at the ADA national meeting, and urged other state chapters to do the same thing.
“It worked,” Crofford says. Thanks to their efforts, those of the Juvenile Diabetes Foundation (now the Juvenile Diabetes Research Foundation) and medical institutions like the Joslin Diabetes Center in Boston, “virtually all of the legislative things that had to be done in order for the diabetes plan to be completed (were) passed,” he says.
In 1977, Congress appropriated $5 million to open five more diabetes centers, and to expand their mission to include the training of diabetes specialists. They are now called Diabetes Research and Training Centers.
The commission also recommended that a study be conducted to determine whether strict control of blood glucose could prevent the disabling and life-threatening complications of diabetes, including blindness, kidney failure, amputation and heart disease.
The NIH asked Crofford to help get it started. “This was a new endeavor for me,” he recalls. “I had never run what we now call clinical trials.” So back to the library he went.
A clinical trial attempts to determine the effectiveness of a drug or other treatment, by comparing one group of patients who receive the treatment to a closely matched group that is not given the treatment and which serves as the “control.”
What made the diabetes study so difficult was that it would require the participation of more than 1,000 patients at multiple research centers over the course of several years.
Despite his relative inexperience, Crofford was a natural to lead the study, his colleagues say. He had continued to advise the NIH on the direction of diabetes research and, in 1981-1982, he served as ADA president. “He was on the ground floor, both from the scientific and public policy aspects,” says Dr. Phillip Gorden, who directed the National Institute of Diabetes and Digestive and Kidney Diseases from 1986 to 1999.
In addition to scientific curiosity, Crofford was motivated by empathy for the plight of his patients. “He saw people having terribly devastating complications from diabetes,” says Vanderbilt research nurse Janie Lipps, who worked with him on the trial and who continues to follow some of the participants. “He wanted to know the truth. Does (controlling blood glucose) really matter?”
This was not the first time that scientists had tried to answer the question.
In 1970 another U.S. study, the University Group Diabetes Program, found no benefit in controlling blood glucose in type 2 diabetics. But it was hampered by the lack of a reliable method for measuring chronic high blood glucose. The hemoglobin A1c test would not become available for several years.
Hemoglobin is the protein in red blood cells that transports oxygen to body tissues. A form of the protein also can bind to glucose, and carry it around for several weeks. Measuring hemoglobin A1c, then, is a way of determining a person’s average blood glucose level over a two- to three-month period.
“That was a very important tool for the clinical trial,” says Dr. David M. Nathan, who, as a young investigator at Harvard Medical School, had helped develop the hemoglobin A1c test. “It gave you this wonderful … timed window on average blood sugar control in a single measurement.”
Two other developments in the 1970s made the study possible: portable glucose monitors, which enabled patients to check their blood glucose conveniently and accurately; and new forms of insulin and insulin pumps, which made it easier for patients to keep their blood glucose within the normal range.
By the early 1980s, the pieces “were all falling into place,” says Nathan, now a professor of Medicine at Harvard and director of the Diabetes Center at Massachusetts General Hospital.
Nathan’s center was one of 29 across the United States and Canada that participated in the study, which focused on patients with type 1 diabetes who had not yet developed complications of the disease, or who had only mild retinopathy, the overgrowth of blood vessels in the retina of the eye that can cause blindness.
Between 1983 and 1989, more than 1,400 participants were enrolled, making the Diabetes Control and Complications Trial (DCCT) one of the largest studies of diabetes ever undertaken.
It was also one of the most difficult. Participants were randomly assigned to a “treatment group” or a “control group,” as is the case in most clinical trials, but those in the treatment group required an unprecedented amount of monitoring by health professionals.
These participants used an insulin pump or gave themselves three or more insulin injections every day, monitored their blood glucose at least four times a day, and adjusted their insulin dose accordingly. They also visited their study center once a month and were in frequent phone contact with the researchers to review and adjust their regimens.
In comparison, participants in the control group gave themselves one or two insulin injections a day, at the time the standard treatment for type 1 diabetes. They did not adjust their insulin dose as frequently, and they were examined once every three months.
Smooth as a United Nations diplomat, Crofford worked to reach consensus and to resolve disputes that could have stopped the study in its tracks.
“I’d say Oscar masterfully allowed, fostered, stimulated, directed and finally concluded those discussions in a way that we had a sound protocol,” says Dr. Saul Genuth, professor of Medicine at Case Western Reserve University in Cleveland, Ohio, who was vice chair of the DCCT and chaired its planning committee. “Oscar pushed us when we needed to be pushed, and he pulled us when we needed to be pulled.”
Just as important to the study’s success were the participants themselves. “They weren’t human guinea pigs,” Crofford says. “They were partners in doing the most important study in diabetes that had ever been done since the discovery of insulin. If they dropped out, they were not only hurting themselves but they might blow the whole study ... So they had to be part of the team.”
Drawing on his experiences in the ADA and Congress, Crofford visited each of the 29 research centers, attending banquets, speaking to participants and encouraging them “to hang in there.”
The results, reported in 1993, showed that strict control of blood glucose dramatically delayed the onset and slowed the progression of three common complications of diabetes -- retinopathy, kidney problems and nerve damage.
There was a downside: Participants in the treatment group were more likely to experience severe hypoglycemia, episodes of low blood glucose that can be life threatening. They also gained more weight on average than those in the control group, a side effect of the more aggressive insulin therapy.
The DCCT was not the only study to demonstrate the benefits of blood glucose control, nor was it the largest. But it set the standard for how a comprehensive and complicated clinical trial should be run, Genuth says.
At Crofford’s insistence, “we made extraordinary attempts to collect good, verifiable, high-quality data, to analyze it by the best bio-statistical means we could, and then to publish our conclusions in a non-speculative, straightforward manner,” he says.
At the same time, Crofford worked with the NIDDK to ensure the study was within its budget, and met federal data management and safety requirements.
“He was astride four horses, if you will,” Genuth says, like Charlton Heston in the movie Ben Hur. “Oscar was the key person in this whole trial in getting all these horses to pull in the same direction ... What it all boils down to is leadership of a quality seldom seen in a randomized, clinical trial.”
The challenge now is to continue to educate health care providers and their patients about the importance of aggressive blood glucose control, and, through advances in technology, make it easier for patients to keep their disease in check.
Many patients don’t have the opportunity to be monitored by nurses and dietitians in the way that study participants were. “The issue is not whether it works or not, but how hard it is to do,” Crofford says. “And believe me, … it’s very difficult for patients to follow a regimen of strict glucose control. It will take technological advances that we do not have today in order for the average person to be able to do that.
“The good news is that even if you’re not perfect, if you make a little bit of improvement, you get a little bit of benefit,” he adds.
Two years after the DCCT ended, Crofford began a new chapter in his life. He and Jane “retired” to his family’s 700-acre spread in the Ozark Mountains to raise Black Angus bulls.
Starting with 12 cattle seven years ago, the Croffords now have about 40 head on their Rocky Bayou Angus Farm, named for the creeks running through it. Mornings and evenings will find them navigating their pastures aboard the four-wheeler and a golf cart, feeding and checking on the livestock with their five dogs in tow.
Crofford hasn’t retired completely from diabetes research. He attends scientific meetings, keeps up with his journals and e-mail, and recently chaired a committee that monitored the progress of another clinical trial.
But he doesn’t spend much time dwelling on the achievements of the past, or brooding over tasks left undone. He’s too busy for that. There are too many new things to learn.
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