“Scientists at the University of Wisconsin in the United States and at Erasmus University Medical Center in the Netherlands say they are voluntarily halting their work for 60 days,” stating “the two months will give governments, international organizations and the scientific community time to determine whether the research can be conducted safely,” VOA News writes (1/21). The WHO is expected to organize a forum in the coming weeks to discuss the issue, Agence France-Presse reports (Sheridan, 1/21). “Suspensions of biomedical research are almost unheard of; the only other one in the United States was a moratorium from 1974 to 1976 on some types of recombinant DNA research, because of safety concerns,” the New York Times notes (Grady, 1/20).

“It’s tremendously concerning that at the same time policymakers and law enforcement professionals are waging a war on the growing prescription drug crisis, new super-drugs could well be on their way, flooding the market,” said Sen. Charles Schumer, D-N.Y. “The FDA needs to grab the reins and slow down the stampede to introduce these powerful narcotics.”

A message seeking comment from the Food and Drug Administration was not immediately returned Friday.

The Associated Press reported last month about addiction experts’ fears over four drugs being tested that contain a more powerful version of one of the nation’s most abused painkillers — hydrocodone.

Schumer is particularly concerned about legalizing the drugs for prescriptions because they would be prized commodities in the black market.

Experts say painkiller addiction has been driven partly by a loophole in the 1970 Controlled Substances Act that classified pure hydrocodone — a super painkiller — as a strictly controlled Schedule II drug. But the law put combination products, such as pills containing hydrocodone and acetaminophen, into the less strict Schedule III.

Because of the loophole, patients can refill a prescription for a hydrocodone-acetaminophen drug like Vicodin up to five times. A prescription for a similar oxycodone product, such as Percocet, can be filled only once. Critics say the loophole has flooded American medicine cabinets with hydrocodone.

In 1999, the Drug Enforcement Administration and FDA began reviewing whether they should reschedule hydrocodone combination products. But an AP review of regulatory documents and court filings shows the agencies have repeatedly passed the rescheduling study back and forth, with no final decision made.

A New Year’s Eve robbery at a Long Island pharmacy netted prescription painkillers and cash and left the robber and a federal agent dead. In June, four died in another Long Island pharmacy robbery in which 11,000 hydrocodone pills were stolen.

If the pure hydrocodone drugs are approved, Schumer wants a “robust post-market surveillance” of the drugs as they are marketed, advertised and sold.

[medpagetoday] Drug research, even from clinical trials sponsored by the federal government, routinely is suppressed, harming patients and increasing healthcare costs, according to a series of reports published by BMJ.

“The current situation is a disservice to research participants, patients, health systems, and the whole endeavor of clinical medicine,” according to an editorial published with the reports.

A solution, according to Richard Lehman, MD, a consultant psychiatrist at the University of Oxford, and Elizabeth Loder, MD, MPH, a contributing editor at BMJ, would be to subject researchers who withhold data to “disciplinary action by professional organizations.”

An unexpected finding in the BMJ analysis was that serious lapses appear to have occurred in clinical trials funded by the National Institutes of Health.

According to the analysis, less than half of NIH-funded clinical trials were published in a medical journal within 30 months of the completion of the trial and after 51 months, one-third of trials remained unpublished.

While industry-related profit motives may not be a factor in such cases, there are other possible explanations, said senior author Harlan Krumholz, MD, of Yale University.

Sometimes researchers may get an unexpected finding that contradicts a position they have staked out, he said.

“It is a conflict of their academic beliefs,” he said.

At the same time, medical journals may not want to publish negative findings, he said.

A second BMJ paper assessed clinical trials of drugs that already had received at least one Food and Drug Administration approval. In such cases a law requires the reporting within one year of the completion of the trial.

Despite the law, only 163 of 738 such trials, or 22%, had reported the results within a year, the paper found.

Lead author Andrew Prayle, PhD, a researcher with the University of Nottingham, in England, said he hoped the finding would spur more researchers to post summaries of the work at the NIH site, ClinicalTrials.gov.

The BMJ papers are just the latest salvos in an ongoing controversy over both industry support of research and control of raw data from trials.

“It is grossly unethical and an insult to the integrity of medicine when this is allowed to occur and go unpunished,” said orthopedic surgeon Chuck Rosen, MD, president of the Association for Medical Ethics.

From diabetes drugs to spine surgery products, scandals involving concealed data have mounted. Consider the cases of a trio of drugs that were the subject of Journal Sentinel/MedPage Today articles:

For two years, Schering-Plough, the maker of the popular cholesterol drug Vytorin, sat on the results of a clinical trial showing the drug provided no benefit in improving artery health. During that time the drug was heavily marketed to consumers in TV ads. The situation came to light in 2008 after a congressional investigation was launched.

In 2003, a clinical trial of Multaq, a drug that treated irregular heart beat, was stopped because more patients who were getting the drug were dying than those who were getting a placebo. However, the study was not published until five years later.

In 2007, an independent analysis of the diabetes drug Avandia found that the drug increased heart attacks and cardiovascular deaths.

Steven Nissen, MD, the lead author of the analysis, said 35 of the 42 studies he looked at were unpublished and were obtained only because a court case required the drug’s maker, GlaxoSmithKline, to turn over the data.

“Had the medical community known about this hazard, Avandia would likely never have become the world’s largest selling diabetes drug,” said Nissen, chairman of cardiovascular medicine at the Cleveland Clinic. “Our ability to provide the best care for patients is dependent on access to all of the available clinical trial evidence, regardless of whether the study showed favorable results.”

While much of the criticism of suppressed medical research has been aimed at drug companies, research data from medical devices also has been delayed, especially when it reflects negatively on a product.

Critics pointed to Medtronic’s bone-growth stimulating back surgery product known as Infuse.

Last year, the Journal Sentinel/MedPage Today reported that the results of a crucial clinical trial of the product were not published until nearly five years after the trial had to be halted because unwanted bone was growing around the spines of the trial volunteers. The paper was written by surgeons who have received millions of dollars in royalties from other Medtronic spine products.

What’s more, the authors of the belated paper downplayed the bone overgrowth, saying it did not harm patients, a claim that was flatly refuted by a doctor interviewed by the Journal Sentinel/MedPage Today.

The doctor, an Oklahoma orthopedic surgeon, said two of his patients who were in the trial had to undergo additional surgery because the bone overgrowth was painfully impinging on nerve roots. One of the patients, a man who was in his 50s at the time, needed three operations — one for the implant, a second to remove the unwanted bone formation, and a third when the additional bone grew back yet again.

Independent research and Journal Sentinel stories since have noted that unpublished data showed that Infuse was linked to a variety of serious complications, including sterility in men and cancer.

The failure of the medical literature to report such findings “has been a major failure in our field,” said Eugene Carragee, MD, a Stanford University orthopedic surgeon and editor-in-chief of the Spine Journal.

Carragee said the BMJ analysis and its call for disciplinary action against offending doctors is “an important departure from the historical laissez-faire attitude of the recent past.”

By John Fauber, Reporter, Milwaukee Journal Sentinel/MedPage

The scientists fear a chill may be descending on their field, particularly related to key studies on how viruses that normally infect birds and pigs evolve to infect people. In the short term, it may also become harder to publish any work looking at this question if it relates to the dangerous H5N1 avian flu.

The panel of biosecurity experts that advised the government on its decision may also recommend that journals agree to a short-term moratorium on publishing research about what makes H5N1 viruses more transmissible.

“We know that there is a lot of research occurring in this specific area and with every paper, the situation changes,” said Paul Keim, an anthrax expert who is acting chair of the National Science Advisory Board on Biosecurity. “Setting policy in such an environment is difficult and it is hard enough already.”

It’s not yet clear that the biosecurity board will ask for the moratorium. Nor is it certain how journals would react to that request if it comes.

But the two journals involved in the controversy, Science and Nature, have both indicated they are at least willing to discuss a compromise, so long as a system can be devised that would give scientists and public health authorities access to the withheld information on a need-to-know basis, CBS News reported.

If the studies are published in abbreviated form, it may be a first for the life sciences. Scientists who work in nuclear physics are often unable to publish their work, for security reasons. But in most areas of science, the paradigm is that if researchers find something or achieve a goal, they must publish how they did the work so that others can try to replicate it and build on it, deterring fraud and ensuring advancement.

Scientists looking for answers that would help the world better assess the risk the H5N1 virus poses are particularly worried that the biosecurity concerns might stop them from seeking answers to questions that might tell the world how likely – or unlikely – bird flu is to adapt to human-to-human spread.

“That is an absolutely key question,” says flu researcher Dr. Malik Peiris, chair of the department of microbiology at the University of Hong Kong. He said restricting this research “would be a huge loss.”

Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases (which funded the two disputed studies), says he’ll fight to keep the biosecurity concerns from restricting science.

“I will do everything in my power to ensure that it doesn’t inhibit the research,” Fauci said. “The research we’re interested in is the legitimate research done by scientists who have a legitimate interest.”

But Dr. D.A. Henderson, who led the campaign that eradicated smallpox, thinks flu researchers have good reason to worry. “I can see where they’d be concerned about it,” Henderson said. “I think we ought to be concerned about working with H5N1.”

Henderson, a distinguished scholar at the Center for Biosecurity at the University of Pittsburgh Medical Center, believes the studies that drew the biosecurity board’s concern should not have been done, that the risks of the work outweighed any potential benefit.

Some researchers agree with Henderson.

“This research should not have been done,” Dr. Richard H. Ebright, a chemistry professor and bioweapons expert at Rutgers University, told the New York Times. “It will inevitably escape, and within a decade.”

But some flu researchers disagree and say these studies had to be done to help humans one day.

“If someone makes a virus, specifically only for making it more pathogenic without learning any biology and in such a way that cannot occur in nature but can only be man-made, then I would be concerned because there is no purpose for this experiment,” says Adolfo Garcia-Sastre, an influenza researcher at Mount Sinai Hospital in Manhattan.

But Garcia-Sastre insists the viruses made in the two studies that triggered this debate could occur in nature. He fears the controversy will lead to more layers of bureaucracy that will box out all but the best financed labs from doing this type of work.

Dr. Michael Osterholm, director of the Center for Infectious Diseases Research and Policy at the University of Minnesota and a member of the panel that advised the government on this decision, said the block may add a sense of urgency to the field.

“I think it will create a temporary slowdown, just because we’re all going to be looking at what should be done, how should it be done and why it should be done,” said Osterholm. “But in the end I think it will actually cause a great acceleration of H5N1 research. Because now that we know what we know, we can make the clear case that we need a lot more research. People can’t write this (virus) off.”

[Nature] Peggy Willocks was 44 when she was diagnosed with Parkinson’s disease. It progressed quickly, forcing her to retire four years later from her job as a primary-school principal in Elizabethton, Tennessee. Soon, her condition had deteriorated so much that she was often unable to dress and feed herself, take care of basic hygiene or walk unaided across a room.

Willocks enrolled in a trial for an experimental therapy called Spheramine, developed by Titan Pharmaceuticals, a biotechnology company in South San Francisco, California. Spheramine consists of cultured human retinal epithelial cells bound to specialized man-made carrier molecules. The cells are implanted into the brain, where it is hoped that they will produce the dopamine precursor levodopa, which can reduce the symptoms of Parkinson’s disease. In August 2000, Willocks became the second person ever to receive the treatment. After having a steel halo — a stereotactic frame — bolted to her skull, she was put under general anaesthesia. Surgeons then used the frame and coordinates obtained from numerous magnetic resonance imaging (MRI) scans to pinpoint the location at which to drill. They then snaked a catheter through her brain’s white matter to deliver the cells into the striatum.

At first there was no effect, but Willocks says that after 6–8 months she began to feel better. The changes were always moderate and gradual, except for once, about nine months after her surgery, when she showed what her doctor called a “radical” improvement in balance. By a year after the treatment, she and the five other patients in the phase I trial showed an improvement in motor ability of 48%, and those gains largely held 4 years later¹.

Ten years on, she says she notices her condition worsening, but is still doing much better than she was before her operation. She has no doubt that the treatment works. Investigators disagree: Spheramine was shelved in 2008 after a follow-up phase II, double-blind study found that it was no more effective than placebo². This time, the researchers compared the treatment with a ’sham’ brain surgery that copied almost every aspect of the procedure Willocks received, short of injecting cells into the brain.

For many investigators aiming to treat Parkinson’s and other neurological diseases invasively, using sham brain surgery as a control is, well, a no-brainer. And the practice is likely to expand in coming years, as researchers continue to develop experimental tissue transplants, gene therapies and stem-cell treatments. Small safety trials such as the one in which Willocks was enrolled may hint at the efficacy of a treatment, but they are not designed to prove it. And because they are ‘open label’ — both the investigators and the participants know that the drug is being administered — they are riddled with biases that can skew results. “It is so clear that open-label studies provide information that is not reliable,” says Warren Olanow, a neurologist at New York’s Mount Sinai Medical Center who has worked on cell-based neurosurgical therapies in Parkinson’s for more than two decades. “It’s almost impossible for me to imagine how a serious scientist can not desire their data or hypothesis to be tested in double-blind studies.”

Other scientists, however, say that sham brain surgery is an expensive, potentially dangerous and possibly unethical bit of biomedical theatrics. It may also be unnecessary. Clinical neuroscientist Roger Barker at the University of Cambridge, UK, contends that because there is huge variation in how these therapies are administered and in how patients respond, the protocols need to be refined in an open-label setting before going on to the next stage of development. And because cost, complexity and the small number of people eligible for such invasive therapies limit the size of the studies, a sham control provides results of limited statistical utility. Barker and his colleagues across Europe are currently enrolling patients in a €12-million (US$17-million) multicentre trial of a fetal dopaminergic nerve-cell treatment for Parkinson’s disease. The treatment may never be tested against a sham-surgery control. “There’s a sort of historical precedent” for using placebo controls, but it may not apply to neurosurgical trials, he says. Willocks and other patients go further. Placebo-controlled studies aren’t just unnecessary, they say, they are actually causing the downfall of potentially valuable treatments.

A complicating control

During the past 25 years, surgical therapies for Parkinson’s disease have travelled a rocky road. In 1987, a report by Mexican surgeons³ described seemingly miraculous effects in two patients with severe Parkinson’s who received transplants of tissue from the adrenal gland, which produces dopamine. In the next several years, hundreds of patients received the treatment, but some autopsies later showed that the cells didn’t in fact survive⁴. Around the same time, researchers started to test fetal nerve-cell transplants (similar to those in Barker’s trial) in small-scale studies, finding mixed but promising results. Two studies^5,6 comparing the treatment to sham surgery concluded, however, that the transplants were not only ineffective, but also often caused dyskinesia — the movement disorder that plagues people with Parkinson’s disease. In the past seven years, three experimental treatments (including Spheramine) that showed promise in small, open-label studies^1,7,8 failed in phase II trials^2,4,9 comparing them with a sham control (see ‘The sham wall’).

Sham brain surgery is no sugar pill. After the stereotactic frame is affixed to the skull, the patient is usually anaesthetized and surgeons drill into the skull. In most cases, the burr holes stop at the dura mater, a protective membrane covering the brain, but they sometimes go deeper: in a phase II trial testing the nerve growth factor GDNF, investigators catheterized the brain in all participants but infused saline, rather than GDNF, into the controls⁹.

“We have to stage the whole thing such that from the outside it’s completely indistinguishable” from the real thing, says Joao Siffert, chief medical officer of Ceregene, a company in San Diego, California, that is working on a therapy that delivers a gene for another nerve growth factor, called neurturin, using a viral vector. For many sham treatments, everyone in the operating room, from surgeons to nurses’ assistants, must pretend that they are busily performing the complete operation — in some cases, turning on machines to elicit appropriate noises. An extremely complex protocol ensures that no one outside the surgical team knows who got what treatment. “It’s very complicated, there are a lot of moving parts,” Siffert says. All that ratchets up the cost of a trial; Siffert estimates that between operating-theatre costs, follow-up and the unwieldy infrastructure required for data management, a 50-patient study would cost more than $10 million.

Still, at least in North America, Parkinson’s disease investigators overwhelmingly support the use of sham surgery — at a rate of 94%, according to a 2004 survey¹⁰. Around 20% said that penetrating the brain is justifiable. And proponents say the procedure is relatively safe. Although sham brain surgery has definite risks, most notably those associated with general anaesthesia, supporters note that adverse events are almost unheard of, unlike the risks of the actual treatments. And participants in the sham groups are generally promised the treatment if it is ultimately approved; in that event, they will already have the burr holes in their skulls through which it would be administered.

Sham treatments help to tease out the placebo effect and biases. In Parkinson’s disease, the placebo effect is especially strong. One reason is that patients’ expectations that they will benefit from a treatment induce the release of dopamine¹¹, the neurotransmitter that is lacking in the disease. “The placebo effect is real, it’s huge and it’s got a physiological basis,” says Jon Stoessl, a neurologist at the University of British Columbia in Vancouver, Canada, who studies Parkinson’s and the placebo effect. In one double-blind study of fetal nerve-cell transplants, patient improvement correlated with whether they believed they had received the treatment, irrespective of whether they actually had¹². And the effect can last as long as two years, Stoessl says, citing an unpublished study by his colleagues.

Many regard bias as a more significant confounder. “Investigators have a tremendous vested interest in seeing that their treatment is effective,” says Anthony Lang, a neurologist at the University of Toronto in Canada who has participated in several neurosurgical trials for experimental Parkinson’s therapies. In any trial, bias can affect how researchers assess patient responses and may inflate the patients’ expectations, further enhancing the placebo effect. Compounding the problem for Parkinsons’ research is the fact that there are no objective measures for how well a patient is doing. “It’s just a sort of perfect storm conspiring against our ability to see definitive changes in the underlying disease,” says Steven Piantadosi, a clinical-trials methodologist at Cedars-Sinai Medical Center in Los Angeles, California. “Sham surgery, properly done, can control for that.”

Barker counters that it is possible to control for investigator bias in an open-label trial by taking steps such as having blinded raters assess patients. His position is in some ways unsurprising; in Europe, sham surgery is deemed much less acceptable than it is in the United States. It has never been used in the United Kingdom. Barker is categorical about his belief that transplantation of fetal tissue works, at least for some people. “I don’t need sham surgery to show that,” he says, pointing instead to a paper¹³ published last year describing two patients treated 13 and 16 years previously who were still benefiting from the treatment, and whose brains showed functional dopamine-producing neurons at the transplant site. He attributes the mixed results in past studies to variation in the patients selected for treatment, the characteristics of the tissue being implanted and the methods used to implant it. His trial will have to demonstrate efficacy without eliciting some of the side effects found in the two sham-controlled studies. That will require some type of control study, he says, but it might take the form of comparison to an approved therapy that is known to work, such as deep brain stimulation.

But time, says Barker, will best establish efficacy. In most trials the end point is no more than a year after the treatment. That may not be long enough: implanted cells or injected growth factors might take longer than this to become fully functional, and the placebo effect may not have had time to dissipate. “We want a 3–5-year endpoint,” says Barker.

There are hints from some of the failed phase II trials that patients followed up beyond study endpoints might tell a more positive story⁴. Some say, therefore, that sham controls are sinking the prospects of valuable drugs. Anders Björklund, a neuroscientist at Lund University in Sweden who is collaborating with Barker, says that sham surgery can lead researchers to throw out a strategy prematurely if the trial fails because of technical or methodological glitches rather than a true lack of efficacy.

Advocacy and frustration

According to Perry Cohen, who leads a network of patient activists called the Parkinson Pipeline Project, that’s exactly what is happening. He had always questioned the need for sham surgery, he says, but after the string of phase II failures, “We started saying, ‘Hey, this is a problem. These trials failed, but we know they are working for some people.’”

For researchers, it is easy to dismiss patients’ concerns as being driven by emotion. “Patients want cures,” says Lang, “and they will often be convinced that the more aggressive, surgical therapies are more likely to be curative.” But Cohen counters that patients have different priorities and that researchers must take these into account. Researchers use placebo controls to weed out false positives. But for patients, the real ogre is the false negatives — which can sink a therapy before it has been optimized. The better a trial is at stamping out the former, the higher the rate of the latter — which means at best delays, and at worst dead ends. Spheramine, for example, “is still on a shelf somewhere”, Cohen says. Then there’s Amgen’s phase II trial of GDNF. The trial was halted in 2004 amid lacklustre results and potential safety concerns, which some have attributed to Amgen’s procedure, rather than to the therapy itself. Now researchers are taking a renewed interest in the molecule, but although Cohen is glad it is getting a second chance, “we lost 6 years on it”, he says.

Patients also have different perspectives on risk from researchers, Cohen says. He offers the story of Tom Intili, who had had Parkinson’s for 10 years when, at the age of 50, he signed on to the double-blind, placebo-controlled trial of neurturin. At first, Intili improved dramatically. But when the results were unblinded, he learned that he had received the sham. His condition plummeted, leaving him more debilitated than he had been before the trial. “We just don’t know what the psychological effects of unblinding are,” Cohen says.

Moreover, trying to exclude the placebo effect is simply misguided, Cohen argues. “I don’t want to subtract out the placebo effect — I want to keep it, because in real life it’s part of the treatment,” he insists. Because psychological factors are so salient in Parkinson’s, a placebo response might actually potentiate a therapy, he explains. “I want to be convinced that sham surgery is necessary. I’m looking for arguments that might change my mind, but I haven’t found any yet,” he says.

Willocks says that she is living proof that many of the recently shelved therapies are in fact salvageable. Of course from a scientific perspective, her story is an anecdote, not data. In May, the failed phase II study of Spheramine — the therapy she received a decade ago — was finally published². The paper closes with a warning about the dangers of the placebo effect and stresses the importance of controlling for it with a double-blind design. “That last paragraph bothered me,” Willocks says. “I just don’t see how they can call it a placebo effect after ten years.” 

Alla Katsnelson is a freelance science writer in New York City.

The agency noted that in 2010, at least 440,000 new cases of multidrug resistant-tuberculosis were detected and the malaria parasite is now developing resistance to the latest generation of medicines. In addition to serious infections acquired in hospitals showing resistance, WHO added that resistance is also emerging against antiretrovirals used to treat HIV. To address the issue, the body outlined a number of measures, including regulating and promoting the rational use of drugs, and fostering innovation and R&D.

Speaking on World Health Day, Chan said the recommendations were aimed “to get everyone, especially governments and their drug regulatory systems, on the right track, with the right measures, quickly.” WHO noted that currently less than 5 percent of drugs in development are antibiotics, and urged the creation of “innovative incentive schemes…to stimulate industry to research and develop new antimicrobial drugs for the future.”

“Can [industry] do more? Yes. But the only way is to really study incentives that will place the industry in a much more comfortable position to continue the development of antibiotics,” remarked Mario Raviglione, head of the WHO’s campaign against tuberculosis. AstraZeneca CEO David Brennan agreed, but noted that “we have to recognise that even if we can increase these numbers, the task will never be complete because our most recently approved and most effective drugs will gradually decline in efficacy and we will need to develop new antibiotics to replace them.”

He suggested that “discovery needs to be underpinned by new financial mechanisms that allow companies to receive a return on their investment in new drugs, while limiting their use to situations of greatest need.” Options include new models for compound sharing in discovery research, the revisiting of previously discarded compounds, and the involvement of public funding in antibiotic R&D. “If leaders in government, science, economics, public policy, intellectual property and philanthropy can come together, we will maximise the opportunities to develop and implement the creative solutions that will truly make a difference to tackling anti-microbial resistance,” Brennan concluded.

The court ruled 6 to 2 that going before a special tribunal set up by Congress is the only way parents can be compensated for the negative side effects that in rare instances accompany vaccinations.  The majority said that Congress found such a system necessary to ensure that vaccines remain readily available, and that federal regulators are in the best position to decide whether vaccines are safe and properly designed.

The National Childhood Vaccine Injury Act of 1986 “reflects a sensible choice to leave complex epidemiological judgments about vaccine design to the FDA and the National Vaccine Program rather than juries,” Justice Antonin Scalia wrote, referring to the Food and Drug Administration. Justices Sonia Sotomayor and Ruth Bader Ginsburg dissented, saying the threat of lawsuits provides an incentive for vaccine manufacturers to constantly monitor and improve their products.

The decision “leaves a regulatory vacuum in which no one – neither the FDA nor any other federal agency, nor state and federal juries – ensures that vaccine manufacturers adequately take account of scientific and technological advancements,” Sotomayor wrote.

The decision is a victory for vaccine makers such as Wyeth and GlaxoSmithKline. Kathleen Sullivan, who represented Wyeth in the case before the court, told justices that ruling against the company could lead to thousands of lawsuits in which parents claim, for instance, that the mumps, measles and rubella vaccine played a role in their children’s autism.

It also marks another chapter in the court’s evolving jurisprudence on “preemption,” the question of when federal laws and regulations displace state actions or lawsuits. Those questions often divide the court on ideological grounds, but in this case, liberal Justice Stephen G. Breyer joined the court’s consistent conservatives.

The Obama administration also backed the vaccine makers, and Justice Elena Kagan was recused because of her work on the case as President Obama’s solicitor general.

The case was brought by Russell and Robalee Bruesewitz on behalf of their daughter Hannah, 18. Hannah began to have seizures as an infant after receiving the third of five scheduled doses of Wyeth’s Tri-Immunol diphtheria-pertussis-tetanus vaccine. The company, now owned by Pfizer, has taken the drug off the market.

The 1986 federal law said that all such claims must first go to a special tribunal commonly called the “Vaccine Court.” The program has awarded nearly $2 billion for vaccine-injury claims in nearly 2,500 cases since 1989. It is funded by a tax on immunizations.

But the tribunal ruled against the Bruesewitzes, saying they had not proved that the vaccine harmed Hannah, who will need lifelong care.

The couple then sued under Pennsylvania tort law. The company had the case moved to federal court, and judges have consistently ruled that the suit cannot proceed, because federal law prohibits claims against “design defects” in vaccines.

The justices at oral argument debated ambiguous wording in the federal law. It says that no vaccine maker can be held liable for death or injuries arising from “side effects that were unavoidable even though the vaccine was properly prepared and was accompanied by proper directions and warnings.”

Scalia said the word “unavoidable” would be meaningless “if a manufacturer could be held liable for failure to use a different design.”

Sotomayor read the language to mean the opposite, and said “text, structure and legislative history compel the conclusion that Congress intended to leave the courthouse doors open for children who have suffered severe injuries from defectively designed vaccines.”

Consumer groups and others had supported the Bruesewitzes, but the American Academy of Pediatrics applauded the decision.

“Today’s Supreme Court decision protects children by strengthening our national immunization system and ensuring that vaccines will continue to prevent the spread of infectious diseases in this country,” AAP President O. Marion Burton said in a statement.

The case is Bruesewitz v. Wyeth.

In other action, the court decided not to revisit its 2005 ruling that struck the display of the Ten Commandments in two Kentucky courthouses.

Lower courts had continued to bar McCreary and Pulaski counties from posting the commandments even though each changed the display to include other religious and historic documents. The court did not comment on why it was not taking the case.

By Robert Barnes, Washington Post Staff Writer, Tuesday, February 22, 2011; 10:46 PM

As absolute and correct as those aphorisms may be, they can be hard for doctors to apply in the complex world of modern medicine.

A recent Medscape medical ethics survey of over 10,000 physicians found that when it comes to patient treatment, a significant number of physicians struggle when it comes to topics relating to honest, straight-forward communication, and even pain management. Physicians from a broad range of specialties answered 3 questions pertaining to patient treatment:

-     Would you ever hide information from a patient about a terminal or preterminal diagnosis, because you believe that it will bolster their spirit or attitude?
-      Would you ever prescribe a treatment that’s a placebo, simply because the patient wanted treatment?
-      Would you ever undertreat a patient’s pain, because of a fear of repercussions or because you are concerned that a patient — even a terminal patient — might become addicted?

Open Communication Is Often Difficult

When it comes to delivering bad news, 59.8% of physicians indicate they “tell it exactly as I see it,” while 14.6% indicate that they soften the news and “give hope even if there is little chance.” Two percent indicate that unless a patient is going to die imminently, they don’t tell him or her how bad the situation is and nearly one quarter (23.8%) say “it depends.”

“The kind of compassion that brings people into medicine is the type of compassion that is needed for delivering bad news,” says Kenneth Goodman, PhD, Director of the Bioethics Program at the University of Miami and author of Ethics and Evidence-Based Medicine: Fallibility and Responsibility in Clinical Medicine. But that compassion should never compromise the truth, he cautions.

Many of the physicians surveyed augmented their responses noting that, while they are honest, they try hard to deliver bad news in the most gentle, humane, and supportive way possible. That’s exactly what patients should expect from their doctors, Goodman advises. But in “softening” the truth, he believes that doctors don’t need to deviate from it.

“If there is something positive you can say, by all means say it. But only tell the truth: ‘I will be there with you. I will help you manage your pain. I will see to it that you can arrange your affairs.’ Those are truthful things,” Goodman says.

When doctors withhold information, they make it more difficult for patients to chart their course and undermine their own credibility.

From the patient’s point of view, “If I don’t know my time is limited I can’t put my affairs in order. I can’t say, ‘I’m sorry,’” he says. What’s more, “it’s not like patients are asking Dr. Kildare, ‘What are my chances, Doc?’ Patients are increasingly educated. If you don’t tell them, they’re going to be looking it up on the internet the next day, so you should probably be the source of the data, because you’re a human and you care about them.”

Goodman advises that the same rationale applies to the use of placebos. Nearly one quarter (23.5%) of respondents said they would prescribe a treatment that was essentially a placebo to a patient simply because he or she wanted treatment. Another 18.2% said, “It depends.”

Physicians who were willing to provide “placebo” treatment generally fell into 2 camps. Some said they would do it to appease a patient but only after telling them it wouldn’t do them any good. One doctor noted that he’d prescribe vitamins and supplements, “but I’d tell them I thought it was worthless”; while another would prescribe a cream for hemorrhoids, “but they are also forewarned” that the treatment wouldn’t do any good.

Still another noted, “In this day and age, many patients will not accept that the best treatment is tincture of time and they have no hesitation about reporting you to the state board or hospital administrator. So, I figure out something that will do the least potential harm and try that.”

Others say they’d be willing to prescribe a benign but ineffectual treatment in hopes of achieving a positive placebo effect. “Placebo works up to 50% of the time,” said one. “Placebos ARE a form of treatment!” noted another and, “Placebo can be psychologically beneficial and I don’t see that as placebo,” wrote a third.

Physicians in the first group need to be able to stand their ground in the face of insistent patients, Goodman advises. After all, they are the medical experts.

“Doctors need to be able to say, ‘I’m sorry, there is nothing I can do,’ No physician is going to provide drugs for a recreational purpose. Why, if a patient asks for an antibiotic for a virus or a prescription that won’t work, should he get it?” Goodman asks. As for those hoping to achieve a placebo effect he notes, if a patient finds out he or she has been prescribed a placebo, it will cause irrevocable damage to the physician-patient relationship.

Pain Management Quandaries

While the first 2 patient treatment questions in the survey pertained to communication, the last addressed pain management. While the overwhelming majority (84.1%) of physicians said they would never undertreat pain, a handful (5.6%) said they would, and about 1 in 10 (10.3%) said they would have to evaluate the situation before making a decision.

After filtering out responses from physicians – many of them emergency department doctors – noting that they routinely deny drug-seeking “frequent fliers” prescriptions for pharmaceuticals, the theme frequently voiced by doctors was that they would undertreat pain due to fear of lawsuits. A number of respondents augmented their answers with frustrated, emotional responses about state medical boards, government intrusion, and litigious patients.

Comments included: “I undertreat not due to concerns about addiction but concerns about Drug Enforcement.” “We live in a real world. I would like to think I would answer ‘no’ if real tort reform took place.” “I bet we all would in today’s drug-abusing, litigious society.” And “The state boards can wreck a doctor without appeal.”

Despite those concerns, others remained steadfast. “I have only the patient to believe as to how much pain they are experiencing. I have been lied to at times over the years, but I would rather try to believe people than to deny everyone because of some bad actors,” wrote one.

When Treatment Denial Causes Suffering

Another noted that physicians’ fears of repercussions have “caused patients to suffer needless pain. If a physician does not feel competent or comfortable handling pain issues, (s)he should refer that patient to a reputable pain specialist. Pain is a legitimate medical condition, which we took an oath to alleviate when possible. If the treatment is appropriate and well documented with the current safeguards in place, there should be no fear.”

Most respondents who elaborated on their answers, however, drew a sharp distinction between patients with chronic conditions and the terminally ill. Many noted that they do not prescribe narcotics to patients with chronic conditions, refer them to pain management specialists, and are vigilant when it comes to chronically ill patients who tend to “lose” prescriptions too often. When it comes to treating the terminally ill, however, respondents spoke in a single voice: treat their pain.

“Terminal patients should be able to get whatever they need whenever they need it,” wrote one. “Terminal patients get whatever they need,” said another. A third noted, “Terminal patients should never be allowed to suffer with pain because of inadequate treatment, especially fear of addiction: what difference does it make if they are going to die addicted to narcotics?”

Or, as one physician summed it up, “Palliative care is humane.”

Steen analysed the number of withdrawals, of academic papers related to the life sciences over the last 10 years. Of the 50 Indian papers withdrawn, 17 — or 34% — were for fraud of some kind, which inclu-des copying findings, making up findings, or fudging findings.

Independent scientists confirmed the result. Bob O’Hara, who writes a statistics blog, has found Indian scientists’ papers are five times more likely to be retracted for fraud than those by scientists of other countries.

Members of the Indian scientific community say there is a systemic problem. “Some of our senior scientists have been involved in fraud,” said Dinesh Abrol, a senior scientist at the National Institute of Science, Technology and Development Studies in New Delhi.

Earlier this year, leaders of the nation’s top science organisations, or academies, had to apologise when a high-level inter-academy report on genetically modified crops was found to contain lifted text.

There are no nationally fra-med rules for punishing research fraud. Institutions are responsible for their own scientists.  The Society for Scientific Values tracks cases, but the organisation is made up of volunteers.

“There is evidence fraud has gone unpunished,” said Abrol.

lowest (worst) E/F [error to fraud] ratio,” said R. Grant Steen, the US-based consultant who carried out the study, published in the Journal of Medical Ethics.