A quick look at the latest developments from Stanford University Medical Center

Illustrations by Paul Blow
(Illustrations cannot be reused without express permission from Stanford Medicine.)

Review process gets scathing review
Shut-eye schedule matters
Medical search engine company sold
Weekend birth no cause for worry
Med school ranking method needs improvement
Drug promotion expenditure quantified


Review process gets scathing review

Keith Humphreys, PhD, knew at the start of his multicenter trial on substance abuse treatment that dealing with institutional review boards — the groups that oversee research involving human subjects – would be difficult. The experience proved so frustrating, though, that he conducted an economic analysis of the process. In the end, the associate professor of psychiatry at Stanford and the VA Palo Alto Health Care System found that in this instance, despite being costly and time-consuming, the IRB procedures had no discernible impact on human subject protection.

Federal Food and Drug Administration regulations give IRBs authority to approve or require modifications in human research. In a multicenter trial, the IRB at the coordinating center must OK the protocol, which is then re-reviewed by IRBs at each participating site.

“The essential procedures of the study never changed substantially, despite exchanges of more than 15,000 pages of material among the nine IRB sites,” Humphreys wrote in the July 1, 2003, Annals of Internal Medicine. He referred to the IRB activities as “$50,000 of paper shuffling.”

High-cost quibbles

For Humphrey’s study on treatment for heroin addiction, the IRBs at participating sites conducted reviews after the protocol was approved by the central IRB. They requested numerous and contradictory revisions to formatting and wording; disagreements involved changes as trivial as saying “study description” instead of “description of study.”
“We spent thousands of dollars doing things like changing the font from Helvetica to Times New Roman,” says Humphreys.

He and his colleagues at the VA found that IRB activities cost more than $56,000, or about 17 percent of the total research grant budget for the study’s first 18 months. Over half of these costs ($29,824) were incurred after the central IRB’s approval.

While agreeing that oversight of human research is crucial, Humphreys says it is important for people to realize the procedure is flawed. Humphreys’ hope is that researchers and policymakers engage in a dialogue on IRB procedures and begin to weigh the cost and benefits of multicenter review for minimal-risk studies.
The economic analysis was funded by the Department of Veterans Affairs Health Services Research and Development Service. – Michelle L. Brandt

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Shut-eye schedule matters

Timing is everything, even when you sleep. People getting just a couple hours of sleep do better if they go to bed early in the morning rather than late at night, suggests medical center research.

"The results were surprising,” says Christian Guilleminault, MD, professor of psychiatry and behavioral sciences and lead author of the paper that appeared in the May 2003 issue of Sleep Medicine. “We had suspected that the more sleep-restricted the participants were, the sleepier they would be — regardless of when they went to bed. That’s not exactly what we found.”


The study, funded by the Sleep Education and Research Foundation of Palo Alto, involved eight men split into two groups: men in one group slept from 10:30 p.m. to 2:30 a.m. for seven nights; men in the other group from 2:15 a.m. to 6:15 a.m. The participants spent the week in the laboratory where researchers tracked their behavior and wakefulness, in part through a test measuring ability to stay awake in a sleep-inducing environment.

The researchers found that the early-morning sleep group’s score on the wakefulness test was significantly better than the late-night sleep group, indicating that early morning sleepers overall were more tolerant of sleep restriction. In addition, the participants kept awake until 2:15 a.m. fell asleep quicker and slept for more of the allotted time.

Everyone is Different

One of the study’s most striking findings was the great variation in individual responses to sleep deprivation, says Guilleminault. He notes that one participant was unaffected by sleep deprivation until the study’s sixth day, while another participant developed severe insomnia.

The unpredictability of a person’s response to sleep deprivation is a good reason for people to be cautious about limiting their amount of sleep, adds Guilleminault. “Abnormal responses will be triggered in some people.”

Among the researchers’ other findings was that the secretion of an appetite-regulating hormone, leptin, decreased significantly during periods of sleep deprivation. Since decreases in leptin are associated with increased appetite, Guilleminault says further studies should focus on a possible link between sleep deprivation and obesity. – Michelle L. Brandt

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Medical search engine company sold

When Stanford launched Skolar in May 2000, the company – formed to market a Web-based medical search engine developed at the medical school – drew considerable attention as the university’s first branded, for-profit spin-off. Skolar’s founder, Stanford professor of medicine Kenneth Melmon, MD, spoke of his vision to revolutionize medicine by giving doctors easy access to medical texts, clinical databases and evidence-based practice guidelines.

In the next year, Skolar partnered with some high-profile firms including Agilent Technologies and Cisco Systems. Next, in 2001 the American Medical Association authorized physician use of the company’s flagship product, SKOLAR MD, to earn continuing medical education credits. By 2002, some 17,000 clinicians had used SKOLAR MD.

Now, after more than a year of silence, comes more news about Skolar: Stanford no longer owns it. In March 2003, Stanford sold Skolar’s assets to the Dutch information services conglomerate Wolters Kluwer.

Officials at Skolar and Stanford say the deal was necessary to ensure Skolar’s survival in the wake of the dot-com bust. Skolar hadn’t turned a profit and needed significant continuing investment.

Stanford professor of medicine Kelley Skeff, MD, chair of Skolar’s editorial board, says the sale will safeguard the legacy of Melmon, who died in 2002, by ensuring Skolar’s financial stability and expanding its content with the addition of Wolters Kluwer products.

“Wolters Kluwer’s philosophy is in sync with the philosophy of Skolar and Ken Melmon — providing comprehensive, high-quality medical information — so the acquisition made a lot of sense,” Skeff says.

Debra Zumwalt, Stanford’s general counsel, says the sale of Skolar to a larger, better-capitalized enterprise had always been envisioned. She added that working with Skolar “was a valuable learning experience for Stanford.” Among
the most important lessons? “Timing is crucial.” – Sara Selis

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Weekend birth no cause for worry

A new study proves false the widespread belief that weekends are more risky for childbirth than weekdays.

Weekend deliveries earned a bad reputation after studies published in the 1970s and ’80s suggested that infants born on weekends have a higher mortality rate. But was this reputation deserved?


Jeffrey Gould, MD, a Lucile Packard Children’s Hospital neonatologist and Stanford professor of pediatrics, led a study that examined the problem more closely, pooling data from more than 1.5 million births throughout California from 1995 to 1997. Gould and colleagues published their findings in the June 11, 2003, Journal of the American Medical Association.

The data revealed why neonatal mortality increased on weekends: Fewer babies are born on weekends – and of these, more are acutely ill, low-birth-weight neonates.

More sick on weekends

But why this pattern? Many physicians prefer to induce labor in women whose fetuses are at risk during the week when ample support staff is available. The same is true of Caesarean sections, which were used to deliver about 20 percent of the infants studied. This tendency to favor weekdays is reflected in the fact that there were 17.5 percent fewer births on the weekend than would have been expected had the births been distributed randomly.

But one type of high-risk birth – premature delivery – can happen anytime.

The researchers found that 0.95 percent of infants born during the week could be classified as “very low birth weight.” In contrast, infants of very low birth weight made up 1.11 percent of all weekend births.

When the researchers correlated mortality rates with birth weight, the difference between weekday and weekend birth mortality vanished, confirming their theory: Proportionally more of the babies born on weekends are acutely ill, creating the perception that weekend births are more dangerous. – Krista Conger

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Med school ranking method needs improvement

Philip Pizzo, Md, Dean of the School of Medicine, believes the annual ranking of medical schools published by U.S. News & World Report is flawed and he’s urging the weekly to change its methodology.

Each spring the magazine comes out with its ranking of graduate schools. In the 2003 report, Stanford placed eighth among research-intensive medical schools.

Pizzo began his push for change last year when he wrote to the magazine’s editors in March and then met with them to propose changes to the ranking methodology. When this spring’s rankings revealed that the editors had not changed the process, Pizzo wrote to them again.

The problem: The ranking methodology values size over quality. Pizzo explains: “U.S. News & World Report weighs most heavily among its criteria the school’s total amount of NIH funding. Stanford ranks highest in the nation for the amount of peer-reviewed NIH funding per principal investigator, but because we are also among the smallest of the research-intensive schools, our total amount of NIH funding is necessarily limited.

“My message is that they should employ a methodology more akin to that used in schools of engineering, whereby they weigh equally the total amount of NIH funding and the NIH funding per principal investigator. That would be much fairer. If this is done for medical schools, it would mean that Stanford would be within the top five schools — more accurately reflecting our true ranking.”

Will the dean’s push for change make a difference? “I’m not optimistic. But I won’t give up,” he says. – Rosanne Spector

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Drug promotion expenditure quantified

The U.S. pharmaceUtical industry spent $12.7 billion promoting its products in 1998, according to estimates by researchers at the Stanford Prevention Research Center.

“We doubt that many physicians and consumers realize how extensive these promotion efforts are and how big an influence they can have on which drugs are sought by and prescribed to patients,” says Jun Ma, MD, PhD, first author of the paper, which appeared in the May 2003 issue of Clinical Therapeutics. Since the primary purpose of drug promotion is marketing – not education – physicians and the public should seek out more objective information, despite the ubiquity of drug industry material, he says.


The study is based on data from the independent pharmaceutical market-research company IMS Health, which surveys the 250 most promoted medications in the United States. Just over half of the promotion funds were funneled to 50 drugs. Overall, the most dominant drug-promotion strategies in 1998 were traditional, time-tested methods. Free samples given to physicians totaled $6.6 billion of retail value, representing 51.9 percent of the drug promotion expenditures. Pitches by drug-industry reps to in-office physicians totaled $3.5 billion, accounting for 27.8 percent of the total. Ads in medical journals totaled $540 million, representing a modest 4.3 percent of total drug-promotion expenditures.

Straight to Consumers

The study also found that direct-to-consumer advertising has become an important component of the pharmaceutical industry’s promotional efforts. Consumer-targeted drug ads totaled $1.3 billion in 1998, representing 10.5 percent of promotional spending.

Randall S. Stafford, MD, PhD, an assistant professor of medicine at the Stanford Prevention Research Center and senior author of the study, explains that physicians should be aware of which drugs are being promoted directly to consumers, so they can prepare to respond to patients’ inquiries.

The research was funded by the Agency for Healthcare Research and Quality and was conducted in collaboration with colleagues at Boston University and the Massachusetts Institute of Technology. – Sara Selis

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