As Pharma beefs about testing, tougher comparative studies may be key

hennepin-300x200Big Pharma howls often about the federal Food and Drug Administration path to get prescription drugs approved for markets, complaining current regulatory processes take too long and, with their requirement for rigorous clinical trials, are too tough.

Even as drug makers seem to be finding sympathetic officials to make these regimens faster and laxer, some voices want the FDA to consider costlier and what they say is more realistic and useful scrutiny of drugs that goes beyond current attempts  to find if they are safe and effective.

Shouldn’t regulators — at the FDA or elsewhere in the federal bureaucracy — help consumers much more to know the answers to “two crucial questions: How do … new therapies compare with already known ones? What are the relative benefits and harms in a particular situation, for a person like you?”

These key queries are cornerstones to “comparative effectiveness” research, says Aaron Carroll, a doctor, a researcher, a professor of pediatrics at Indiana University School of Medicine, and a regular contributor to the New York Times’ evidence-based column, “The Upshot.”

Carroll says it’s becoming more and more important for patients to get evidence-based information to help them decide which of many medical options they should pursue — at what cost and with what outcomes? He says doctors and hospitals are themselves too often in the dark about one course of care against another:

Consider antibiotics. In my work as a pediatrician, questions about their use come up a lot. Which drug is the best first-line therapy for which common illnesses? We don’t know. How long should we treat for different infections? We don’t know. What are the relative trade-offs between benefits and side effects in different patients in different circumstances? We don’t know.

He also reports on treatments for high blood pressure, a condition that some specialists see afflicting almost half of all American adults. Carroll says there are the main drugs used to treat hypertension. But a $100 million study, involving more than 33,000 patients over four years at more than 600 centers across the United States and Canada, apparently hasn’t settled the issue of which of the three courses of care works best for different patients, including those with early and mild hypertension versus those who have chronic and uncontrolled high blood pressure. The results point to which therapy doctors ought to consider for which patients but a debate rages still in the medical community, Carrol reports.

In my practice, I see the harms that patients suffer while seeking medical services, and their struggles to determine how best to access and afford safe, effective, and even excellent medical care. This is especially true when patients confront daunting choices about prescription drugs with sky-high costs and uncertain outcomes or that even may be risky and downright dangerous.

Carroll doesn’t address them specifically in his column on comparative effectiveness, but it’s also fair to note concern has grown about cancer drugs and the wild promotion that has surrounded innovative therapies that also come with staggering prices, with many averaging around $100,000 annually and some launching with costs exceeding $400,000 annually. Although they’re hyped as life changing and saving and major advances over their precursors, new cancer drugs may not be all that, as critics have pointed out.

Vinay Prasad, a doctor and assistant professor of medicine at the Oregon Health and Sciences University,  has written extensively about the FDA’s approval process for cancer drugs, and as CNN reported he has argued that:

Many more drugs, however, have offered patients only marginal benefits, with no evidence that they improve survival or quality of life … Overall cancer survival has barely changed over the past decade. The 72 cancer therapies approved from 2002 to 2014 gave patients only 2.1 more months of life than older drugs, according to a study in JAMA Otolaryngology-Head & Neck Surgery. And those are the successes. Two-thirds of cancer drugs approved in the past two years have no evidence showing that they extend survival at all.

The National Institutes of Health and the Patient Centered Outcomes Institute, Carroll says, are two lonely standouts in trying to conduct the kind of comparative studies that he argues that patients, doctors, and hospitals need. It’s not easy, fast, or cheap work. Others should join in.

A caution on a comparative ‘study’

Meantime, there also may be a cautionary counterpoint to some of the clear benefits that real-world comparative research might yield: This case involves a much criticized “study” conducted in emergency room treatment at Hennepin Healthcare in Minnesota (see photo above). There, doctors and emergency medical services (EMS) crews decided to test on severely agitated patients which of two powerful sedatives helped calm them better: ketamine or midazolam. They developed their own guidelines as to which drugs would be given to which patients and they got around rigorous rules on human subjects testing by dubbing their work “an observational study.”

But as a post on KevinMD by Ruth Macklin, a PhD and professor of epidemiology and population health at the Albert Einstein College of Medicine, noted, the Minnesota “study” fast became an ethical dumpster fire. In practical terms, police — who work closely with EMS crews — pressured the medical personnel too often to sedate unruly subjects, whom they deemed “severely agitated,” because many were criminal suspects they wanted help detaining.

Then critics assailed the “study,” because information leaked out that doctors and EMS crews had decided they need not get patients informed consent to be drugged or to participate in the “research” with “minimal risk” and “medical necessity,” allowing them, instead, to “opt out” at a later point. As critics emphasized for the wayward medical personnel, however, informed consent is a crucial and fundamental patient right. It says that it’s every health care provider’s duty to ensure that you know fully your treatment options, and that you decide what path to take, without your being subjected to strong-arming, scare tactics, or misleading information from anyone, no matter their fancy degrees, medical specializations, or surgical reputations.

A public outcry — with indignant defenses from medical officials that they were doing a good and right thing — halted the unacceptable Minnesota comparative drug “study.” But as Macklin reported, this did not occur before patients also suffered harm: “Some individuals were restrained prior to injection. There were clearly consequences, as some of those injected suffered heart or breathing failure and had to be revived. Intubation was required in some cases.”

Photo credit: HCMC, Minnesota © SusanLesch, Creative Commons

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