Psychiatrist Finds Niche in Clinical Trials Testing

During a career that has spanned four decades and taken him around the globe, Ari Kiev, M.D., J.D., has studied everything from folk psychiatry in Haiti to community psychiatry in England. A graduate of Harvard College, Cornell University Medical College and New York Law School, he has also published widely on suicide, acted as chairman of the psychiatry division of the U.S. Olympic Council in Sports Medicine, consulted to Wall Street stock traders and written numerous scientific texts plus books for consumers. Those latter include Recovery From Depression (E.P. Dutton 1982), The Courage To Live (Bantam Books 1982) and the recently rereleased A Strategy for Daily Living, (The Free Press 1997), which was an April Book-of-the-Month Club alternate selection.

But one of his major challenges has been his role as founder and director of the Social Psychiatry Research Institute (SPRI), one of a growing number of independent investigator sites across the country that specialize in the complex process of conducting clinical trials for new medicines (see related story). With sites in New York and New Jersey, SPRI has since its inception in 1970 worked on more than 100 studies for psychiatric drugs developed by major pharmaceutical companies including Wyeth-Ayerst, Eli Lilly & Co., Smith-Kline Beecham Pharmaceuticals, Pharmacia & Upjohn, Pfizer Inc., Solvay Pharmaceuticals, Bristol-Myers Squibb, Burroughs Wellcome and Janssen Pharmaceutica.

Speaking from his New Jersey office, Kiev, who as both a psychiatrist and lawyer writes for scientific journals about the rigorous process of conducting clinical trials, recalled the events that led him to a career in psychopharmacology research.

He said his first love, an interest in other cultures, began while an undergraduate at Harvard, where he majored in social relations--"a combination of sociology, anthropology and psychology"--and wrote his honors thesis on healing practices in primitive cultures. After receiving his medical degree in 1959, he did a residency at Johns Hopkins Hospital, where he worked on a major anxiety study conducted by Eberhard Uhlenhuth, M.D., and Karl Rickels, M.D., pioneers in treating anxiety disorders. He next spent a year as a research fellow at the Institute of Psychiatry at Maudsley Hospital in London, and during that time published his first papers on folk psychiatry and psychiatric epidemiology.

In 1962, he became a U.S. Air Force staff psychiatrist at Lackland Air Force Base in Texas, continuing to publish scientific papers on transcultural psychiatry, work that resulted in the publication in 1964 of his first book: Magic, Faith and Healing: Studies in Primitive Psychiatry (The Free Press of Glencoe), a text which continues to be a staple of anthropology courses. That same year, he went as a research associate to the department of psychiatry at Columbia University's College of Physicians and Surgeons, where he became field station director of the Psychiatric Epidemiology Research Unit under Ernest Gruenberg, M.D., and started working in private practice with depression pioneer Nathan S. Kline, M.D., who shared Kiev's interest in transcultural psychiatry.

"Kline was the discoverer of marsilid and reserpine, and the developer of lithium and many other early medicines used in psychiatry," Kiev recalled. "He was a brilliant pioneer, and I spent six years with him learning the fundamentals of research in psychopharmacology."

Kiev said that part of Kline's mission was to introduce modern psychiatric clinics in developing countries, an interest that led Kiev to work at one of those clinics in Haiti.

"Medicine seemed to be one of the most useful forms of treatment in less-developed cultures where there were few psychiatrists," Kiev said. "There was also some linkage between using medicine and working with traditional and native healers."

In 1967, he joined Cornell University Medical College to head the Cornell Program in Social Psychiatry.

"The program was originally established by Alexander Leighton, M.D., who went on to become a professor at Harvard," Kiev said. "Its mandate was to do research in the field of social psychiatry and it had done the pioneering Midtown Manhattan study, which revealed a large number of psychiatric symptoms in the general population. "

Continuing his own previous work in psychiatric epidemiology, Kiev was awarded a National Institute of Mental Health grant to study the natural history of attempts at suicide. That research led to a number of publications on suicide as well as a number of books, including the bestseller A Strategy for Daily Living, which was first published in 1973 and revised and rereleased this year.

In 1970, he was approached to do a clinical trial for two antidepressant medications. It was then that he formed SPRI as an independent research institute.

"It was simply easier to separate that [clinical trial] from the research we were doing at Cornell by setting up SPRI," he said. "I also received a grant from the city to study the treatment of drug addicts in the therapeutic community called Project Return. I did that out of the Institute as well, and continued my transcultural studies there."

Kiev remained program head at Cornell until 1974, and then joined the voluntary faculty where he's since remained as a clinical associate professor. In 1975, he did a CBS Sunrise Semester program called Magic, Faith and Healing, 45 half-hour lectures based on his 1964 book. And at SPRI, he continued his independent research while maintaining a private clinical practice and developing Life Strategy Workshops, intensive two- to three-day seminars which began for suicidal patients and gradually expanded to agoraphobic patients and then to other groups such as Olympic athletes and more recently, traders on Wall Street.

"The institute supported many projects, including going around the world several times to visit Africa, Asia and India to study psychiatric practices and film religious and healing rites and rituals," said Kiev. "That was my principle interest and the drug studies were a subsidiary interest."

But as funding for his transcultural work got harder to obtain, and Kiev became increasingly expert at conducting clinical trials, that part of his work grew.

"We began to do more and more studies, primarily with depression, and worked on the pivotal trials for almost all of the SSRIs, in addition to medications for OCD and panic disorder," he said.

Recently, as the emphasis in psychiatric research has begun to expand into the area of novel schizophrenia compounds, SPRI began involvement in a number of schizophrenia studies in collaboration with several regional hospitals, said Kiev.

"Our work has also expanded to include several satellite offices in nursing homes where we've been conducting studies of some of the newer antipsychotic medications in agitated Alzheimer's patients," Kiev added. "We're also studying the use of an antidementia drug in the treatment of vascular dementia."

Kiev, who conducts about five clinical trials a year, said the endeavor is "tremendously labor-intensive." His New York site has a staff of eight to handle telephone screening, clinical ratings, medical evaluations and coordination of studies. Additional staff are based in New Jersey. The two sites, plus other satellite sites, are linked by computer networks, and professional monitors are employed to do quality assurance work.

"We're about the same size as a number of freestanding investigational sites around the country run by other clinician investigators," said Kiev. "I struggle with the issue of size, but it's absolutely necessary to have highly skilled telephone screeners, coordinators, raters and others to do quality work, as time constraints and paperwork demands escalate."

Getting eligible patients is not easy, said Kiev.

"We might screen 100 patients who call in response to a really time-tested ad for depressed patients, and of those 100 screened, maybe 30 are eligible to come in," he explained. "Of the 30 invited in, maybe 20 show, and of those, maybe 10 turn out to be really eligible. And of those 10, maybe five have clean labs. So it's a lot of work to get the eligible patients, and the more experienced you are, the more willing you are to do the work so that you don't get people who are not compliant or people with borderline medical conditions."

All staff must take satisfaction in solving logistical problems, he added, because throughout studies there are repetitive breakdowns.

Said Kiev: "The EKG gets stuck, the blood sample gets lost by Federal Express, a patient's relative forgets to give the medicine on time. There's a train strike or a snowstorm and a patient can't get in to start medication, so you have to find a way to get that patient."

Another important factor is having a check-and-balance system to adhere to protocol and regulations requirements. "Informed consent is critical, and it is easy to slip up on getting everything signed and making sure the patient really understands it. It's easy to miss a prohibited concomitant medication or schedule an appointment at the wrong time. You really have to make sure to do everything right by having a system of checks and balances and rules set up so that procedures govern the day rather than your own desires to put a patient on a study. This is really difficult to do alone; at least one-fourth of my staff is checking the other three-quarters all the time."

Kiev, who has written journal articles about informed consent, said protection of the patient is critical, right down to the type of ad an organization might run to recruit patients.

"You must be very explicit that it's a research medicine study, but I notice a lot of ads out there that aren't," he said. They'll say 'come to our specialty clinic' and say nothing about a study, or they don't put in all the cautionary statements."

Continued Kiev: "What's interesting is that 27 years ago, we were probably the first people to put an ad in the New York Times. Back then, that kind of thing was looked at askance and continued to be looked at that way for another 20 years. But now it's common even for universities to advertise, because they're pressed by loss of government funds."

So is conducting trials profitable? Not really, said Kiev."It's an activity that generates profit margins of 10% to 20%, depending on how well-managed the studies are. Like many research institutes that have been developed in physician's offices, SPRI has often been subsidized by my private practice and personal funds, especially during lulls."

But while conducting trials has not been a huge moneymaker, it is extremely satisfying.

"My motivation has really been to contribute to the development of new treatments for the mentally ill, to be at the cutting edge where you're working with these drugs before they even come out," he said. "We've participated in pivotal trials for a number of compounds including fluoxetine, fluvoxamine, paroxetine, venlafaxine and many others. The labor-intensiveness and difficulty is a real challenge, and every new study brings a new kind of challenge."

Kiev, who still devotes two-and-a-half days to his private practice, also functions as counsel and cocounsel to several law firms in psychiatric legal cases.

"For years, I'd been called in as an expert in suicide and psychopharmacology cases, so when I turned 50 I finally decided to attend law school, graduating in 1988," he said.Kiev said that everything in his career has been a natural progression of his initial interests.

"The apparently diverse activities are all related and derive from the same perspective and desire to contribute to the betterment of humankind," he said. "I'm driven to do a variety of things, but it's always the same dimension emerging, to help others find peace of mind or personal fulfillment, or in the case of my legal career, justice."

Kiev stresses his debt to other people.

"Increasingly over the past five years, I've become very much aware that everything I do depends very much on others," he said. "I may set the overall tone, direction and pace, but I couldn't have done most of what I've done without the inspiration of my parents' lives, the support of my wife who has believed in all my dreams, and the teamwork and enthusiasm of my staff and colleagues."