At the beginning of Ronald R. Gauch's aptly titled It's Great! Oops, No It Isn't, the author juxtaposes two headlines that appeared seven years apart. The first was "Hormones Cut Women's Risk of Heart Disease," from the San Francisco Chronicle in 1994.
The second: "Hormones Don't Protect Women From Heart Disease, Study Says," from The Washington Post in 2001.
Over the next 26 chapters, Gauch, an associate professor of public administration at Marist College in New York, delves deeply into the factors — from laboratory culture to media hype — that helped write those headlines. The result is an authoritative, thorough tome on every aspect of modern medical research; Gauch devotes six chapters alone to "understanding the clinical trial," widely considered the gold standard for research but, as Gauch painstakingly proves, prone to inconsistent protocols and outcomes.
Neither an invective nor a defense, It's Great! Oops, No It Isn't offers a behind-the-study look at how medical research is actually conducted, from the first protocol design to publication of the results. Along the way, Gauch makes clear that he believes the vast majority of individual scientists running these trials are "ethical, inventive and inspired professionals." But the process can be badly flawed, vulnerable to manipulation, fraud, bias and an array of factors beyond the researchers' control. And Gauch has plenty of ideas for how the Food and Drug Administration should begin enacting reforms.
This is not, however, a book aimed principally at doctors, chief scientists or policy analysts; as Gauch notes with some satisfaction, "There is not a single formula in it." Instead, Gauch's target audience consists of anyone who's ever complained that the medical community can't seem to make up its mind about, say, red wine: Is it good for the heart or isn't it (in moderation, of course)? As a result, Gauch's book studiously avoids technical jargon and remains eminently readable, even when describing minute differences between trial designs.
Gauch's informed, occasionally bemused tone shoots down the notion that clinical trials are just too complicated for non-medical professionals to understand. Equal parts narrative history and practical manual, Gauch's book should be a must-read for anyone considering participating in a clinical trial.
He uses the efforts to establish a link between tobacco and lung cancer to introduce the history of medical research, illustrating the stringent standards of "proof" required in the scientific community. For many Americans, the decades-long debate between tobacco companies and cancer researchers represented an introduction to the idea that only a controlled trial, carefully designed to weigh all relevant demographic and genetic factors, could provide the definitive answer to a science-based question.
"Yet that smallest, slightest, infinitesimal possibility that cigarette smoking is not a cause of lung cancer cannot be totally eradicated even today," Gauch notes. "In part this is because the 'gold standard test,' a comparative clinical trial of smokers and non-smokers, has never been conducted."
Gauch describes that gold standard test as the "backbone of medical progress" and credits the clinical trial with increasing survival rates for breast, uterine, prostate and bladder cancer. Nevertheless, the clinical trial has come under fire in recent years, and in 2005, a prominent medical researcher controversially declared in the journal PLoS Medicine that most clinical research findings are false.
While Gauch doesn't go nearly that far, the crux of his book is a discussion of the "seven deadly flaws" that comprise the clinical trials' Achilles heel, ranging from "the imperfect sample" to "the impractical result." In his view, the gold standard has lost a great deal of its luster over the past several decades, as increasing influence from the pharmaceutical companies and venture capital firms that fund clinical studies causes serious conflicts of interest.
"The relationships among industry, scientific investigators and academic institutions are pervasive," he writes. "One investigation, led by S. Krimsky, a Tufts University professor, reported that lead authors in one of every three articles published hold relevant financial interests in a company that would be affected by the outcome."
Gauch's book is crammed full of similar studies; indeed, some of its most compelling information is drawn from medical journals turning an investigative eye on their own industry. For instance, Gauch cites a confidential survey of medical statisticians by the International Society for Computational Biology in 2000, which found that "half of the interviewees knew of at least one fraudulent project, 25 percent reported knowledge of fabrication and falsification, one in five were aware of deceptive reporting of data and 20 percent knew of cases in which data were suppressed."
When Gauch analyzes the recent controversies in medical research — notably, the furor over Vioxx, the hugely profitable medication for arthritis that was withdrawn from shelves after fears it led to increased risk for heart attack and stroke — he does an admirable job of going beyond the headlines. He examines how budgetary cuts at the FDA led to lapses in regulatory activities and lays blame equally at the feet of the government and the drug company, Merck.
In the chapter titled "Research Results that Clashed — What's the Right Answer?" Gauch examines both sides of the regulatory divide. From mammography to female contraceptive devices to aspirin, Gauch explores how different research and cost-benefit analysis methods can lead to "definitive" studies that come to opposite conclusions, all but arguing with each other. And in an increasingly entrepreneurial society, Gauch fears new avenues to present medical research could result in an even more chaotic and unfair system.
The solution, according to Gauch, is streamlining the system to "increase the timeliness, thoroughness and accuracy of medical findings." He'd like to see a detailed public registry of clinical trials, more stringent monitoring of newly approved drugs and a greater use of patients' case reports once drugs hit the market. But the key, in his view, is ensuring that comparative clinical trials remain as bias-free as possible. He is also encouraged by legislation passed in 2007 that gives the FDA more regulatory power over a drug's warning labels, television commercials and public disclosures.
Still, we've come a long way since the first clinical trials, which amounted to little more than battlefield surgeons trying new ways to save soldiers' lives (with wildly varying degrees of success). Throughout It's Great! Oops, No It Isn't, Gauch uses historical anecdotes and passages from centuries-old medical journals to offer compelling and sometimes comedic contrasts with the stainless-steel labs and spotless white coats of today. He discusses an 1816 doctoral thesis from the University of Edinburgh that describes how 366 soldiers were allocated to three military surgeons. The soldiers received equivalent care, but one of the physicians practiced bloodletting as part of his treatment while the others did not. The bloodletting physician saw 35 of his patients die compared to an average of three deaths for the other two physicians, who did not engage in bloodletting.
"The amazing result was so strong," Gauch notes wryly, "it did not require a sophisticated statistical analysis to be convincing."
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