Heralded medical treatments often fail to live up to their promise

By Alan Bavley and Scott Canon, The Kansas City Star

Monday, May 26, 2014 | 2 a.m.

KANSAS CITY, Mo. — For the millions of people who couldn't get their high blood pressure under control even with handfuls of pills, a simple procedure was going to be the breakthrough.

Burn away hypersensitive nerves in the kidneys. Watch blood pressure readings go down.

The American Heart Association hinted that the procedure, renal denervation, might become a drug-free cure, even for mild cases of high blood pressure. Media reports highlighted great results of preliminary research.

Patients eager to get off their meds started calling hospitals.

"The potential benefit was huge," said Kamal Gupta, a cardiologist at University of Kansas Hospital.

If only it had worked.

In March, doctors reported data from the first truly rigorous study. Patients' blood pressure did drop, but it fell just as much among those who got a fake version. Device manufacturers canceled additional studies.

"This could be considered the biggest disappointment in cardiology of this century," Gupta said. But, he added, "the medical community went about it right."

If only that were always the case.

A combination of industry marketing, overly eager doctors, demanding patients and news media ready to cheer on anything that sounds like a breakthrough is popularizing many drugs, surgeries and other treatments long before they're adequately tested. Far too often, they're ultimately proved ineffective, no better than older, cheaper therapies, or even hazardous.

Billions of dollars are wasted and tens of millions of patients are put at risk.

Remember Vioxx, the pain pill for arthritis? It was prescribed to 80 million people worldwide from the time the Food and Drug Administration approved it in 1999 to 2004, when its manufacturer, Merck, withdrew it from the market as evidence emerged that it raised the risk of heart attack and stroke. The FDA said Vioxx caused an additional 88,000 to 138,000 heart attacks and sudden cardiac deaths in the U.S. alone.

Or consider arthroscopic knee surgery. Doctors were doing about 650,000 of these procedures per year at a cost of about $5,000 each. It seemed to relieve pain in about half the arthritis patients who had it done. Then in 2002, researchers compared results of the surgery to a sham version of the operation. Patients got just as much relief when the surgery was fake. As with renal denervation, it turned out to be a costly placebo.

"There's a tendency by doctors and patients to believe that newer is better and more expensive is better and higher tech is better," said Richard Deyo, a physician on the faculty of Oregon Health and Science University and co-author of "Hope or Hype: The Obsession With Medical Advances and the High Cost of False Promises."

"The truth is, it really is very difficult, even within the medical profession, to distinguish the really important advances from things that aren't."

Right now, hospitals are investing millions to buy surgical robots and hundreds of millions to build proton beam cancer radiation facilities performing so-called bloodless surgery. Both are technological marvels. But even as the money is spent, the medical evidence remains unclear whether they're better than conventional methods.

What is clear: With serious money at stake, the advertising and marketing of these technologies is unrelenting.

"Marketing drives much more of medicine than most people like to admit. When it comes to high-paying procedures, particularly when they're reimbursed by Medicare and private insurance in our fee-for-service health care system, doctors and hospitals compete for patients," said Ivan Oransky, a physician and investigative journalist who is global editorial director of MedPage Today.

"We've all seen the billboards for robotic surgery and bloodless operations. We've fetishized 'cutting-edge.' When it sounds shiny and new, doctors can be very persuasive and take advantage of patients' natural tendency to think they have their best interests in mind."

Journalists charged with "feeding the beast of the daily news cycle" also whip up enthusiasm for the latest medical treatments, said Gary Schwitzer, a former CNN medical reporter turned academic.

Schwitzer has been critiquing the work of his former colleagues for nearly a decade. Earlier this month, he published a study that reviewed the quality of 1,889 medical news stories. It wasn't flattering.

"Drugs, medical devices and other interventions were usually portrayed positively; potential harms were minimized, and costs were ignored," his study said.

Reporters often "don't have the time or don't have the expertise to scrutinize claims or to evaluate evidence," Schwitzer said.

This will only get worse, he predicted, as major news organizations demand briefer stories.

"I fear what lies ahead."

While patients, and perhaps some journalists, may be excused for their lack of medical expertise, doctors also are swept up by medical hype.

"There's a reason why doctors are so easily fooled," Deyo said.

What persuades doctors is what "makes sense," he said. Doctors see their patients get better after a treatment, so they reason that the treatment must work.

But doctors can fall into a logical fallacy called "post hoc ergo propter hoc," that just because event X happens after event Y, Y must have caused X: The sun rises because the rooster crowed.

Likewise, just because a patient seems to get better doesn't mean that the treatment received was responsible.

There's the well-known placebo effect on patients. Believing that a procedure will work can make a difference.

And sometimes patients just heal on their own, with no help from the procedure or drug they received. Some patients have conditions like arthritis that vary in cycles from mild to severe.

"People come in when they're feeling their worst. Sometimes they would have gotten better on their own," said Josephine Briggs, a nephrologist and director of the National Center for Complementary and Alternative Medicine. "That can skew your perception of a treatment."

Gartner Inc., an information technology research and advisory company, analyzes medical and other innovations through what it calls "hype cycles."

They typically represent a roller coaster of overenthusiasm and disillusionment. The former accompanies great promises — yet another promising cure for cancer or a device to treat heart disease. The latter comes with the brutal complexities of science — a technique that makes physiological sense but disappoints in practice, or it works but comes with horrific side effects.

"We think we can do this, then, oh, we've got an event that shows ... it's not safe or it doesn't work as well as we hoped," said Vi Shaffer, Gartner's vice president of research for health care. "It's not steady. You get excited. You get disappointed. Then some things exceed our expectations."

The unpredictability of the cycle gives researchers, device makers, drug companies and patients reason to temper their hopes, she said. But Shaffer said it also calls for the sort of patience that will give innovations the funding and testing needed to bring them to market and to monitor their use in the years after.

•••

Medical history is full of lessons about breakthroughs that went from promise to disaster.

Hormone replacement therapy used to be a rite of passage for women entering menopause. By 1992, one of these hormone pills, Premarin, a combination of estrogen and progestin, had become the best-selling prescription in America.

Demand for hormone therapy began to build in the 1960s and 1970s as newspapers and women's magazines, even a best-selling book, claimed that a condition called "estrogen deficiency" was responsible for many of the ailments of aging. Hormone replacement therapy was the promised fountain of youth that would make women happier.

But there had been only one long-term study supporting estrogen to prevent chronic illnesses, and it involved too few women to be considered conclusive. In the early 1990s, the National Institutes of Health launched the Women's Health Initiative, two large studies in which women received estrogen alone, estrogen plus progestin, or placebo pills.

A decade later, the results came as a bombshell. The estrogen/progestin combination didn't do any better than a placebo at preventing chronic diseases in postmenopausal women, but it did increase the risk of breast cancer, heart attack, stroke and blood clots. Estrogen alone raised risks of stroke and blood clots.

The number of women on hormone replacement therapy dropped nearly 70 percent. Experts credited that for an almost immediate decline in breast cancer cases.

Last year, the Women's Health Initiative reported follow-up data, reaffirming that for women in their 50s, hormone replacement therapy may be safe enough in the short term to relieve menopause symptoms. But risks were higher among older women, and there wasn't reliable data on risks or benefits of long-term use.

Bone marrow transplants were being used successfully by the 1960s and '70s as a last-chance therapy for people with leukemia. But in the 1980s, several small studies reported hopeful results for women with breast cancer, and the treatment soon became a cause celebre.

Many women who were desperate for a cure clamored for the treatment, even though it was grueling and risky. With research scant, insurance companies were skeptical about paying the $80,000 cost. But this was the era of managed care, and insurance companies were not well-liked.

Women's health advocates, politicians and the patients' lawyers protested, applied pressure and filed lawsuits. The media, including "60 Minutes," provided sympathetic coverage.

Ultimately, many insurers relented. During the 1990s, more than 42,000 women received bone marrow transplants for breast cancer costing a total of $3.4 billion, according to one estimate. But by the end of the decade, results of large studies began to come in, most showing no advantage over conventional chemotherapy and significantly greater complications that could be lethal.

The transplants killed from 3 to 15 percent of the women who got them.

•••

The verdict is still out on some of the most expensive new technology.

Surgical robots have arms that operate on patients as a surgeon sits at a console manipulating hand and foot controls. The hope is that they can lead to less bleeding and shorter hospital stays.

Even though they cost about $1.5 million each, hospitals have been snatching them up. In 2008, robots played roles in 114,000 surgeries. By 2012, that number had risen to 367,000.

The extra costs get passed to patients. A study published last year found the average hospital bill was $8,868 for a robot-assisted hysterectomy, compared with $6,679 for conventional laparoscopic surgery. Although the robot's patients were less likely to be hospitalized for more than two days, there was no significant difference between the two types of surgery in complications or numbers of blood transfusions needed.

Meanwhile, complaints have mounted about the devices, including more than 70 lawsuits in which patients alleged they suffered complications. The FDA in December issued a recall for two components of the machines.

With proton beams, radiation can be directed not only at a certain spot on the body, but limited to a fairly precise depth. That's been shown to be helpful at sparing healthy tissue when aiming the beam at tumors surrounded by the eyes, brain or spinal cord.

But the larger market is for more common cancers, like prostate tumors. From 2006 to 2009 alone, the number of proton therapy cases for prostate cancer that were billed to Medicare increased 67 percent.

Proton beam therapy is nearly twice as costly. Medicare pays about $19,000 for a full dose of standard radiation for prostate cancer and more than $32,000 for proton treatments.

Yet, according to the American Cancer Society, there's no convincing evidence that proton therapy does a better job curing prostate cancer or preventing the common complications, mainly incontinence and erectile dysfunction, of conventional radiation.

While it's scientifically valid to believe proton therapy is better, "the clinical data just isn't mature yet," said Justin Bekelman, an assistant professor of radiation oncology at the University of Pennsylvania. "It's likely that it's as good, possible that it's better. It's possible that it's worse. Articles (in medical journals) have shown all of those."

•••

Good studies, the kinds that use placebos or sham procedures as controls, are essential to determining the true value of many new medical therapies.

But such studies often require large numbers of patients to be followed for years at a time, and that's expensive, Deyo said. Industry studies are geared toward receiving FDA approval of a drug or device and shedding "the most favorable light" on the product, he said.

That usually leaves the job of funding of studies to the federal government, he said.

The renal denervation study was an exception. It was sponsored by Medtronic, one of the manufacturers making devices for the procedure.

The would-be market was enormous. About 78 million American adults have high blood pressure; only half have it under control. Wall Street estimated that sales of the new devices needed to perform renal denervation could reach $3 billion per year.

"I do think there was quite a bit of hype about this procedure at first, and with good reason. We were getting good results," said Jason Lindsey, a cardiologist at St. Luke's Hospital, which participated in Medtronic's study.

But Lindsey agrees that much of that benefit may have been due to the placebo effect. And patients enrolled in clinical trials tend to be more conscientious about taking their medications.

"I do think that effect was seen in that trial," he said.

St. Luke's was going to participate in two more renal denervation studies this year. They have been called off.

Unless manufacturers re-engineer their devices and commission new studies, renal denervation won't be an option that doctors will be offering patients any time soon.

"I think we're all in limbo about where this technology will go," Lindsey said.