In theory, CER sounds like a calm, academic subject: evaluate different treatment options for a given illness — drug A vs drug B, or drug A vs surgery — and determine which does a better job of reducing morbidity and mortality. You also can go a step further and compare these treatment options in terms of risks or cost-effectiveness: Does drug B outperform drug A by a 2% margin but cost 3 times as much? Experts say such research is in short supply, leading to poorer clinical outcomes and runaway costs.

However, talk of government-sponsored CER pushes hot buttons in medicine and American society alike, being called “rationing” and “government takeover of medicine.” For proof, consider what happened when the US Preventive Services Task Force announced last November that, based on the scientific evidence it weighed, it no longer recommends mammograms for women aged 40 through 49 years. The task force also recommended that women aged 50 years and older no longer receive annual mammograms but, instead, get them every other year. Public outcry and pushback from several medical societies and expert groups like the American Cancer Society swayed Senate Democrats to rewrite their pending healthcare reform legislation to guarantee mammogram coverage.

If Congress enacts healthcare reform, more such medical recommendations could roil Americans. That’s because reform bills passed by the House and Senate (which have yet to be reconciled) call for the creation of a CER entity that would question the value of many trusted procedures and treatments. These provisions come on top of economic stimulus legislation passed in early 2009 that pumps $1.1 billion into CER and establishes a new federal bureaucracy to manage it. The government would not conduct CER itself by and large but would instead fund the work of academic investigators.

NEJM Authors Bolster Support for CER Individual physicians and medical societies approach CER with varying degrees of enthusiasm, cautious support, and downright fear and loathing. The 2 recent NEJM articles seek to bolster support for this controversial discipline. Two professors at Weill Cornell Medical College, New York City, write in an article titled “Health Care Reform and the Need for Comparative-Effectiveness Research” that CER is “physicians’ first line of defense against blind cost containment.” Furthermore, it could spur drug and medical device manufacturers “to develop products that really matter.” “I think CER is the physician’s best friend,” coauthor Alvin Mushlin, MD, professor and chair of the Department of Public Health at Weill Cornell, told Medscape Medical News. Similarly, the other NEJM article, titled “Comparative Effectiveness and Health Care Spending — Implications for Reform,” warns that without a shift to best-bang-for-the-buck services identified by CER, cost-cutting alone could produce worse health outcomes. “If we can induce hospitals and health plans to improve efficiency and not just cut costs, then health costs in the United States will come down and outcomes will improve,” write coauthors Milton Weinstein, PhD, a professor of health policy and management at the Harvard School of Public Health, Boston, Massachusetts, and Jonathan Skinner, PhD, a professor of economics at Dartmouth Medical School, Hanover, New Hampshire. Proposed Government-Sponsored CER Would Be Transparent The American Medical Association (AMA) and several other medical societies believe that the federal government can play a valuable role in CER. After all, the cost of this research deters drug and device manufacturers from studying how their products fare in head-to-head competition with others; plus, they may be afraid to tell the world that their product is second-best, according to AMA President J. James Rohack, MD. The government would not operate under these constraints. Furthermore, government-sponsored CER would be a public, transparent enterprise. In contrast, said Dr. Rohack, private payers that conduct CER to determine what they’ll cover don’t always reveal how they’ve reached their decisions — the proverbial, and hated, black box. “You don’t know if they’re just trying to maximize profits or if science backs up their coverage determination,” Dr. Rohack told Medscape Medical News. Accordingly, the AMA and its medical allies have mostly supported provisions in healthcare reform legislation that make the federal government a player in CER. The House bill establishes a Center for Comparative Effectiveness Research within the Agency for Healthcare Research and Quality in the US Department of Health and Human Services. Findings from this center could not be construed as mandates regarding treatment, coverage, or payment, but some experts interpret the legislation as giving the center the ability to make recommendations. In contrast, the Senate bill would create a nonprofit, independent Patient-Centered Outcomes Research Institute that is confined to only publishing its findings and is explicitly prohibited from issuing even recommendations. The AMA prefers the Senate approach because it’s more emphatic about denying a CER body any policy-making clout. The association also prefers an independent body. In contrast, the CER center in the House bill would be a fiefdom within Department of Health and Human Services, which also operates the Medicare and Medicaid programs. There’s fear in some quarters that a CER group embedded in the federal bureaucracy would be vulnerable to political bullying, with scientific integrity sacrificed on the altar of budget-cutting. However, an independent body also comes with risks, said Neil Kirschner, PhD, a senior associate in regulatory and insurer affairs for the American College of Physicians (ACP), a strong advocate of government-sponsored CER. “The public-private group that the Senate wants could be unduly influenced by the private sector,” Dr. Kirschner told Medscape Medical News. “The ACP hasn’t taken a position on which approach is right.” Dr. Kirschner said the ACP would like government-sponsored CER to freely factor in cost-effectiveness data. “The Senate bill makes this more difficult,” he said. “The House bill is more silent on the use of cost.” Cost-effectiveness, he added, doesn’t necessarily mean adopting the least-expensive treatment. “Sometimes the most expensive treatment may be a better value by helping a person live much longer,” he said. Give Physicians Scientific Findings, Not Recommendations Both the ACP and the AMA agree that a government-sponsored CER body should forgo recommendations, much less mandates, on how physicians should practice medicine. For one thing, private insurers and government programs like Medicare are tempted to turn such recommendations into binding policies that may arbitrarily deny patients coverage for needed care, explained the AMA’s Dr. Rohack. “Look at vaccines,” Dr. Rohack told Medscape Medical News. “The federal Advisory Committee on Immunization Practices recommends what vaccines should be administered, and insurers key off that to determine what they’ll pay for.” The fracas over mammograms last year occurred at the intersection of recommendation and insurance coverage, noted health-policy analyst Dennis Smith from the Heritage Foundation, a conservative think tank. “The essential benefit package in the [original] Senate reform bill was supposed to include preventive services recommended by the US Preventive Services Task Force. So if you didn’t meet the [task force] criteria, you wouldn’t get your mammogram paid for.” Dr. Rohack also pointed to the problem of inflexible application of CER. A study that identifies the best way to treat a particular medical condition may have excluded patients older than 65 years, for example. A payer may then decide to cover that treatment, but not for anyone older than 65 years, he said. It’s sufficient, said Dr. Rohack, to give CER findings to physicians and patients and let them make the final decision on medical care. “Physicians by training try to use evidence-based science to do what’s best for patients,” he said. “If there is a gray zone, they’ll rely on history, experience, and local practice styles. And there are gray zones.” Dr. Rushlin at Weill Cornell Medical College agrees with Dr. Rohack that merely publishing CER findings without adding recommendations will benefit healthcare. “We need to get started incorporating information from CER into the public debate on healthcare. It can be a very positive step in the right direction,” he said. “When you put the evidence on the table, it illuminates the discussion. It doesn’t eliminate the discussion. That’s healthy.” Rationing With a Light Touch? Despite all the restrictions in the House and Senate healthcare reform bills, government-sponsored CER alarms some physicians, such as the American Association of Physicians and Surgeons. An opponent of reform legislation, the society states on its Web site that CER “will provide the rationale for rationing” and suggests that this discipline is a reincarnation of managed care. Sen. Thomas Coburn, MD (R-OK), wrote in the Wall Street Journal last month that CER is one reason why “seniors will die sooner” if Congress passes the Senate’s version of healthcare reform. In other countries, such as the United Kingdom, Dr. Coburn wrote, CER panels amount to rationing panels. Dr. Weinstein and Dr. Skinner acknowledge in their article that Americans have less of a stomach for explicit, top-down rationing of healthcare resources than other countries in which CER has a longer history. The authors point out, however, that Americans appear more amenable to rationing when it’s based on free-market price decisions, such as whether to pay a higher copayment for more expensive medication. With that tendency in mind, Dr. Weinstein and Dr. Skinner suggest several ways to coax patients and providers to veer toward cost-effective care without getting heavy-handed about it. Physicians and hospitals could receive higher compensation when they perform more cost-effective services, and lower compensation when they choose more wasteful services. Likewise, consumers purchasing insurance could pay a higher premium for a plan that would give them immediate access to higher-cost medications, for example, without first having to try less expensive ones — read generics — to see whether they work. N Engl J Med. Published online January 6, 2010.

[nytimes]  Melissa J. Whitaker has one very compelling reason to keep up with the health care legislation being written in Washington: her second transplanted kidney.

The story of Ms. Whitaker’s two organ donations — the first from her mother and the second from her boyfriend — sheds light on a Medicare policy that is widely regarded as pound-foolish. Although the government regularly pays $100,000 or more for kidney transplants, it stops paying for anti-rejection drugs after only 36 months.

The health care bill moving through the House of Representatives includes a little-noticed provision that would reverse the policy, but it is not clear whether the Senate will follow suit. The 36-month limit is one of several reimbursement anomalies — along with inadequate primary care payments and incentives that encourage unneeded care — that many in Congress hope to cure.

Ms. Whitaker, 31, who describes herself as “kind of a nerd,” has Alport syndrome, a genetic disorder that caused kidney failure and significant hearing loss by the time she was 14. In 1997, after undergoing daily dialysis for five years, she received her first transplant. Most of the cost of the dialysis and the transplant, totaling hundreds of thousands of dollars, was absorbed by the federal Medicare program, which provides broad coverage for those with end-stage renal disease.

Despite that heavy investment, federal law limits Medicare reimbursement for the immunosuppressant drugs that transplant recipients must take for life, at costs of $1,000 to $3,000 a month.

Once Ms. Whitaker’s Medicare expired, she faced periods without work and, more important, without group health insurance, which disregards pre-existing conditions. Struggling financially, she soon found herself skipping doses of anti-rejection drugs.

By late 2003, her transplanted kidney had failed, and she returned to dialysis, covered by the government at $9,300 a month, more than three times the cost of the pills. Then 15 months ago, Medicare paid for her second transplant — total charges, $125,000 — and the 36-month clock began ticking again.

“If they had just paid for the pills, I’d still have my kidney,” said Ms. Whitaker, who shares an apartment in the La Jolla neighborhood with her boyfriend, Joseph D. Jamieson. “I’d be healthy, working and paying taxes.”

The Medicare program is not sure how many of the country’s 100,000 transplant recipients are without insurance for their immunosuppressant drugs. Officials with the National Kidney Foundation said some dialysis patients never put themselves on transplant lists because they fear that they will not be able to afford the drugs.

Currently unemployed, Ms. Whitaker is nervous that in two years she will again find herself without health coverage. She and Mr. Jamieson, who have been together five years, said they would marry if necessary so he could insure her under the group policy provided by his employer, the drug manufacturer Pfizer. But nothing is guaranteed.

“If Joe were ever to lose his job or medical coverage, I do feel it would be possible for me to find myself without insurance again,” said Ms. Whitaker, who reads lips to compensate for her hearing loss. “I’m extremely nervous about whether I’m going to be able to afford my medications once my coverage runs out.”

Bills have been introduced in Congress since 2000 to lift the 36-month limit and extend coverage of immunosuppressant drugs indefinitely. They have never made it to a vote, largely because of the projected upfront cost; the Congressional Budget Office estimates that unlimited coverage would add $100 million a year to the $23 billion Medicare kidney program.

But the cost-benefit analysis would seem obvious. The most recent report from the United States Renal Data System found that Medicare spends an average of $17,000 a year on care for kidney transplant recipients, most of it for anti-rejection drugs. That compares with $71,000 a year for dialysis patients and $106,000 for a transplant (including the first year of monitoring).

“It doesn’t make any sense at all,” Ms. Whitaker said. “Somebody’s not looking at the numbers.”

A provision to cover the drugs is in the sweeping House health care bill, which has cleared three committees. It is uncertain whether the Senate Finance Committee will include it in its bill.

Since 1973, end-stage renal disease has been the only condition specifically covered by Medicare regardless of age. In 1988, coverage was extended for 12 months to anti-rejection drugs, which had recently been developed. Congress gradually lengthened the cutoff to 36 months, and then in 2000 made the benefit unlimited for those who are at least 65 or disabled. The rationale for leaving out younger transplant recipients was simply that the money was not there, Congressional aides said.

Ms. Whitaker was married when her Medicare eligibility expired after her first transplant, and her husband was able to insure her under his group policy. They divorced in 2001, and she became uninsured until taking a job at Kinko’s that provided health benefits.

Her downward spiral began the day she awoke to find that her dog had used her hearing aids as a chew toy. She could not afford replacements and had to leave her job because she was unable to interact with customers.

She lived in Seattle for a while without electricity or hot water. The bank repossessed her car, and she filed for bankruptcy. Her grandmother eventually bought her new hearing aids, and she went back to work. But she was laid off a year later.

“That’s when I started stretching out the pills,” she said. “I’d take one in the morning and one at night, instead of two. Toward the end, I ran out of pills and was taking nothing for a couple of months. I figured I was young and could make it until I found insurance.”

She figured wrong. When she arrived at an emergency room, weak from weight loss and anemia, her doctors told her they were surprised she was not in a coma. The kidney, they said, had not been functioning at all.

“I felt really guilty because it was my mom’s kidney and I broke it,” Ms. Whitaker said.

Ms. Whitaker moved back to Southern California to live with her mother, and soon met Mr. Jamieson. He is seven years younger and, at 6-foot-8, stands 16 inches taller, but they had what Mr. Jamieson calls “a mutual dork synchronicity” (they share a passion for video games). He bought her a stuffed kidney, with a ureter nose, and almost immediately offered her one of his kidneys.

She declined. “I didn’t want to start dating somebody and steal his kidney,” she said. “That seemed kind of rude.”

Several years later, she reversed course and accepted the transplant on June 10, 2008. She has suffered several minor rejection episodes, but lately has been feeling well.

The couple gets by on Mr. Jamieson’s paycheck and Ms. Whitaker’s Social Security benefits. With the help of financial aid, she recently completed two years at a community college and will soon start classes at the University of California, San Diego. She said she hoped a degree would help her find a job with health coverage, perhaps as an addiction counselor.

But her bigger hope is that Congress will eliminate the 36-month limit so she can pursue any job, without concern for insurance.

“My whole life is dictated by my illness, and it’s such a waste,” Ms. Whitaker said. “If the government is going to spend all that money to help people get a kidney, they should help you keep it.”

The case stemmed from a patient admitted to Martin Memorial Medical Center, in South Florida. In 2003, the hospital faced a dilemma: For three years, it had been caring for day laborer Luis Jimenez, who’d been hit by a drunk driver and left a paraplegic with brain damage. The hospital had spent $1.5 million treating him. Now it wanted to transfer him to a cheaper, long-term care facility.

Carla Luggiero of the American Hospital Association says hospitals face limited options for patients with no insurance and no legal status.

“We could help find a charity bed, or subsidize them at a nursing home, or send them home to relatives,” Luggiero says. “Or we could keep them indefinitely. And in that case, that patient is utilizing a bed that could be used for someone who has a more acute health care need.”

When no other facility would take Jimenez, Martin Memorial turned to another option. Early one morning, against the wishes of Jimenez’s cousin and legal guardian, the hospital chartered a plane for $30,000 and flew Jimenez to Guatemala. The government there had said it would care for him in a hospital. But he was soon discharged, and now lives with his mother, bed-bound, in a remote mountain-top village.

“He has no medical care there to speak of, and he’s having an increasing number of seizures and increasing in intensity,” says Bill King, the lawyer for Jimenez’s guardian.

Jimenez’s family had sought damages, plus $1 million to cover the lifetime cost of his care in Guatemala. The Florida jury rejected that claim.

Luggiero says the case might make hospitals more comfortable transferring patients to their home countries, something she estimates happens once or twice a month. But others believe the high-profile case will have a different impact.

“What it is mostly likely to do for a lot of hospitals and a lot of patients is have a chilling effect on the front end,” says Larry Gage, who heads the National Association of Public Hospitals and Health Systems.

Gage says publicly funded hospitals — by law — must stabilize someone in crisis. That doesn’t always mean admitting them.

“Hospitals may well try to define in as limited a way as possible their obligations to the patient [who] shows up at the emergency room,” Gage continues. “And I think you’ll see hospitals tightening up on their policies to try to mirror the reality of what they’re going to get paid to do.”

There’s another aspect to the case: A state judge originally approved Jimenez’s repatriation. But an appeals court later overturned that. It said state judges have no power to decide immigration cases. It was too late for Jimenez, but lawyer Bill King hopes that the ruling sends a message to hospitals.

“You can’t just decide to remove a foreign national, an undocumented person, and send them into what we contend, of course, was a medical abyss,” King says. He plans to appeal the jury decision denying damages to Luis Jimenez’s family.

In a statement, Martin Memorial Medical Hospital said the most disappointing part of this case is that the issue of providing health care for undocumented immigrants remains unresolved. Unfortunately, the hospital says, none of the health care overhauls being debated in Congress would address it.

-Jennifer Ludden

[NYT] PETER SINGER – You have advanced kidney cancer. It will kill you, probably in the next year or two. A drug called Sutent slows the spread of the cancer and may give you an extra six months, but at a cost of $54,000. Is a few more months worth that much?

The costs of the current health care system are becoming increasingly clear, and public sentiment for a more systematic approach may be growing. We’d like to know what you think about the prospect of rationing.

If you can afford it, you probably would pay that much, or more, to live longer, even if your quality of life wasn’t going to be good. But suppose it’s not you with the cancer but a stranger covered by your health-insurance fund. If the insurer provides this man — and everyone else like him — with Sutent, your premiums will increase. Do you still think the drug is a good value? Suppose the treatment cost a million dollars. Would it be worth it then? Ten million? Is there any limit to how much you would want your insurer to pay for a drug that adds six months to someone’s life? If there is any point at which you say, “No, an extra six months isn’t worth that much,” then you think that health care should be rationed.

In the current U.S. debate over health care reform, “rationing” has become a dirty word. Meeting last month with five governors, President Obama urged them to avoid using the term, apparently for fear of evoking the hostile response that sank the Clintons’ attempt to achieve reform. In a Wall Street Journal op-ed published at the end of last year with the headline “Obama Will Ration Your Health Care,” Sally Pipes, C.E.O. of the conservative Pacific Research Institute, described how in Britain the national health service does not pay for drugs that are regarded as not offering good value for money, and added, “Americans will not put up with such limits, nor will our elected representatives.” And the Democratic chair of the Senate Finance Committee, Senator Max Baucus, told CNSNews in April, “There is no rationing of health care at all” in the proposed reform.

Remember the joke about the man who asks a woman if she would have sex with him for a million dollars? She reflects for a few moments and then answers that she would. “So,” he says, “would you have sex with me for $50?” Indignantly, she exclaims, “What kind of a woman do you think I am?” He replies: “We’ve already established that. Now we’re just haggling about the price.” The man’s response implies that if a woman will sell herself at any price, she is a prostitute. The way we regard rationing in health care seems to rest on a similar assumption, that it’s immoral to apply monetary considerations to saving lives — but is that stance tenable?

Health care is a scarce resource, and all scarce resources are rationed in one way or another. In the United States, most health care is privately financed, and so most rationing is by price: you get what you, or your employer, can afford to insure you for. But our current system of employer-financed health insurance exists only because the federal government encouraged it by making the premiums tax deductible. That is, in effect, a more than $200 billion government subsidy for health care. In the public sector, primarily Medicare, Medicaid and hospital emergency rooms, health care is rationed by long waits, high patient copayment requirements, low payments to doctors that discourage some from serving public patients and limits on payments to hospitals.

The case for explicit health care rationing in the United States starts with the difficulty of thinking of any other way in which we can continue to provide adequate health care to people on Medicaid and Medicare, let alone extend coverage to those who do not now have it. Health-insurance premiums have more than doubled in a decade, rising four times faster than wages. In May, Medicare’s trustees warned that the program’s biggest fund is heading for insolvency in just eight years. Health care now absorbs about one dollar in every six the nation spends, a figure that far exceeds the share spent by any other nation. According to the Congressional Budget Office, it is on track to double by 2035.

President Obama has said plainly that America’s health care system is broken. It is, he has said, by far the most significant driver of America’s long-term debt and deficits. It is hard to see how the nation as a whole can remain competitive if in 26 years we are spending nearly a third of what we earn on health care, while other industrialized nations are spending far less but achieving health outcomes as good as, or better than, ours.

Rationing health care means getting value for the billions we are spending by setting limits on which treatments should be paid for from the public purse. If we ration we won’t be writing blank checks to pharmaceutical companies for their patented drugs, nor paying for whatever procedures doctors choose to recommend. When public funds subsidize health care or provide it directly, it is crazy not to try to get value for money. The debate over health care reform in the United States should start from the premise that some form of health care rationing is both inescapable and desirable. Then we can ask, What is the best way to do it?

Last year Britain’s National Institute for Health and Clinical Excellence gave a preliminary recommendation that the National Health Service should not offer Sutent for advanced kidney cancer. The institute, generally known as NICE, is a government-financed but independently run organization set up to provide national guidance on promoting good health and treating illness. The decision on Sutent did not, at first glance, appear difficult. NICE had set a general limit of £30,000, or about $49,000, on the cost of extending life for a year. Sutent, when used for advanced kidney cancer, cost more than that, and research suggested it offered only about six months extra life. But the British media leapt on the theme of penny-pinching bureaucrats sentencing sick people to death. The issue was then picked up by the U.S. news media and by those lobbying against health care reform in the United States. An article in The New York Times last December featured Bruce Hardy, a kidney-cancer patient whose wife, Joy, said, “It’s hard to know that there is something out there that could help but they’re saying you can’t have it because of cost.” Then she asked the classic question: “What price is life?”

Last November, Bloomberg News focused on Jack Rosser, who was 57 at the time and whose doctor had told him that with Sutent he might live long enough to see his 1-year-old daughter, Emma, enter primary school. Rosser’s wife, Jenny, is quoted as saying: “It’s immoral. They are sentencing him to die.” In the conservative monthly The American Spectator, David Catron, a health care consultant, describes Rosser as “one of NICE’s many victims” and writes that NICE “regularly hands down death sentences to gravely ill patients.” Linking the British system with Democratic proposals for reforming health care in the United States, Catron asked whether we really deserve a health care system in which “soulless bureaucrats arbitrarily put a dollar value on our lives.” (In March, NICE issued a final ruling on Sutent. Because of how few patients need the drug and because of special end-of-life considerations, it recommended that the drug be provided by the National Health Service to patients with advanced kidney cancer.

The costs of the current health care system are becoming increasingly clear, and public sentiment for a more systematic approach may be growing. We’d like to know what you think about the prospect of rationing.

There’s no doubt that it’s tough — politically, emotionally and ethically — to make a decision that means that someone will die sooner than they would have if the decision had gone the other way. But if the stories of Bruce Hardy and Jack Rosser lead us to think badly of the British system of rationing health care, we should remind ourselves that the U.S. system also results in people going without life-saving treatment — it just does so less visibly. Pharmaceutical manufacturers often charge much more for drugs in the United States than they charge for the same drugs in Britain, where they know that a higher price would put the drug outside the cost-effectiveness limits set by NICE. American patients, even if they are covered by Medicare or Medicaid, often cannot afford the copayments for drugs. That’s rationing too, by ability to pay.

Dr. Art Kellermann, associate dean for public policy at Emory School of Medicine in Atlanta, recently wrote of a woman who came into his emergency room in critical condition because a blood vessel had burst in her brain. She was uninsured and had chosen to buy food for her children instead of spending money on her blood-pressure medicine. In the emergency room, she received excellent high-tech medical care, but by the time she got there, it was too late to save her.

A New York Times report on the high costs of some drugs illustrates the problem. Chuck Stauffer, an Oregon farmer, found that his prescription-drug insurance left him to pay $5,500 for his first 42 days of Temodar, a drug used to treat brain tumors, and $1,700 a month after that. For Medicare patients drug costs can be even higher, because Medicare can require a copayment of 25 percent of the cost of the drug. For Gleevec, a drug that is effective against some forms of leukemia and some gastrointestinal tumors, that one-quarter of the cost can run to $40,000 a year.

In Britain, everyone has health insurance. In the U.S., some 45 million do not, and nor are they entitled to any health care at all, unless they can get themselves to an emergency room. Hospitals are prohibited from turning away anyone who will be endangered by being refused treatment. But even in emergency rooms, people without health insurance may receive less health care than those with insurance. Joseph Doyle, a professor of economics at the Sloan School of Management at M.I.T., studied the records of people in Wisconsin who were injured in severe automobile accidents and had no choice but to go to the hospital. He estimated that those who had no health insurance received 20 percent less care and had a death rate 37 percent higher than those with health insurance. This difference held up even when those without health insurance were compared with those without automobile insurance, and with those on Medicaid — groups with whom they share some characteristics that might affect treatment. The lack of insurance seems to be what caused the greater number of deaths.

When the media feature someone like Bruce Hardy or Jack Rosser, we readily relate to individuals who are harmed by a government agency’s decision to limit the cost of health care. But we tend not to hear about — and thus don’t identify with — the particular individuals who die in emergency rooms because they have no health insurance. This “identifiable victim” effect, well documented by psychologists, creates a dangerous bias in our thinking. Doyle’s figures suggest that if those Wisconsin accident victims without health insurance had received equivalent care to those with it, the additional health care would have cost about $220,000 for each life saved. Those who died were on average around 30 years old and could have been expected to live for at least another 40 years; this means that had they survived their accidents, the cost per extra year of life would have been no more than $5,500 — a small fraction of the $49,000 that NICE recommends the British National Health Service should be ready to pay to give a patient an extra year of life. If the U.S. system spent less on expensive treatments for those who, with or without the drugs, have at most a few months to live, it would be better able to save the lives of more people who, if they get the treatment they need, might live for several decades.

Estimates of the number of U.S. deaths caused annually by the absence of universal health insurance go as high as 20,000. One study concluded that in the age group 55 to 64 alone, more than 13,000 extra deaths a year may be attributed to the lack of insurance coverage. But the estimates vary because Americans without health insurance are more likely, for example, to smoke than Americans with health insurance, and sorting out the role that the lack of insurance plays is difficult. Richard Kronick, a professor at the School of Medicine at the University of California, San Diego, cautiously concludes from his own study that there is little evidence to suggest that extending health insurance to all Americans would have a large effect on the number of deaths in the United States. That doesn’t mean that it wouldn’t; we simply don’t know if it would.

The costs of the current health care system are becoming increasingly clear, and public sentiment for a more systematic approach may be growing. We’d like to know what you think about the prospect of rationing.

In any case, it isn’t only uninsured Americans who can’t afford treatment. President Obama has spoken about his mother, who died from ovarian cancer in 1995. The president said that in the last weeks of her life, his mother “was spending too much time worrying about whether her health insurance would cover her bills” — an experience, the president went on to say, that his mother shared with millions of other Americans. It is also an experience more common in the United States than in other developed countries. A recent Commonwealth Fund study led by Cathy Schoen and Robin Osborn surveyed adults with chronic illness in Australia, Canada, France, Germany, the Netherlands, New Zealand, the United Kingdom and the United States. Far more Americans reported forgoing health care because of cost. More than half (54 percent) reported not filling a prescription, not visiting a doctor when sick or not getting recommended care. In comparison, in the United Kingdom the figure was 13 percent, and in the Netherlands, only 7 percent. Even among Americans with insurance, 43 percent reported that cost was a problem that had limited the treatment they received. According to a 2007 study led by David Himmelstein, more than 60 percent of all bankruptcies are related to illness, with many of these specifically caused by medical bills, even among those who have health insurance. In Canada the incidence of bankruptcy related to illness is much lower.

When a Washington Post journalist asked Daniel Zemel, a Washington rabbi, what he thought about federal agencies putting a dollar value on human life, the rabbi cited a Jewish teaching explaining that if you put one human life on one side of a scale, and you put the rest of the world on the other side, the scale is balanced equally. Perhaps that is how those who resist health care rationing think. But we already put a dollar value on human life. If the Department of Transportation, for example, followed rabbinical teachings it would exhaust its entire budget on road safety. Fortunately the department sets a limit on how much it is willing to pay to save one human life. In 2008 that limit was $5.8 million. Other government agencies do the same. Last year the Consumer Product Safety Commission considered a proposal to make mattresses less likely to catch fire. Information from the industry suggested that the new standard would cost $343 million to implement, but the Consumer Product Safety Commission calculated that it would save 270 lives a year — and since it valued a human life at around $5 million, that made the new standard a good value. If we are going to have consumer-safety regulation at all, we need some idea of how much safety is worth buying. Like health care bureaucrats, consumer-safety bureaucrats sometimes decide that saving a human life is not worth the expense. Twenty years ago, the National Research Council, an arm of the National Academy of Sciences, examined a proposal for installing seat belts in all school buses. It estimated that doing so would save, on average, one life per year, at a cost of $40 million. After that, support for the proposal faded away. So why is it that those who accept that we put a price on life when it comes to consumer safety refuse to accept it when it comes to health care?

Of course, it’s one thing to accept that there’s a limit to how much we should spend to save a human life, and another to set that limit. The dollar value that bureaucrats place on a generic human life is intended to reflect social values, as revealed in our behavior. It is the answer to the question “How much are you willing to pay to save your life?” — except that, of course, if you asked that question of people who were facing death, they would be prepared to pay almost anything to save their lives. So instead, economists note how much people are prepared to pay to reduce the risk that they will die. How much will people pay for air bags in a car, for instance? Once you know how much they will pay for a specified reduction in risk, you multiply the amount that people are willing to pay by how much the risk has been reduced, and then you know, or so the theory goes, what value people place on their lives. Suppose that there is a 1 in 100,000 chance that an air bag in my car will save my life, and that I would pay $50 — but no more than that — for an air bag. Then it looks as if I value my life at $50 x 100,000, or $5 million.

The theory sounds good, but in practice it has problems. We are not good at taking account of differences between very small risks, so if we are asked how much we would pay to reduce a risk of dying from 1 in 1,000,000 to 1 in 10,000,000, we may give the same answer as we would if asked how much we would pay to reduce the risk from 1 in 500,000 to 1 in 10,000,000. Hence multiplying what we would pay to reduce the risk of death by the reduction in risk lends an apparent mathematical precision to the outcome of the calculation — the supposed value of a human life — that our intuitive responses to the questions cannot support. Nevertheless this approach to setting a value on a human life is at least closer to what we really believe — and to what we should believe — than dramatic pronouncements about the infinite value of every human life, or the suggestion that we cannot distinguish between the value of a single human life and the value of a million human lives, or even of the rest of the world. Though such feel-good claims may have some symbolic value in particular circumstances, to take them seriously and apply them — for instance, by leaving it to chance whether we save one life or a billion — would be deeply unethical.

Governments implicitly place a dollar value on a human life when they decide how much is to be spent on health care programs and how much on other public goods that are not directed toward saving lives. The task of health care bureaucrats is then to get the best value for the resources they have been allocated. It is the familiar comparative exercise of getting the most bang for your buck. Sometimes that can be relatively easy to decide. If two drugs offer the same benefits and have similar risks of side effects, but one is much more expensive than the other, only the cheaper one should be provided by the public health care program. That the benefits and the risks of side effects are similar is a scientific matter for experts to decide after calling for submissions and examining them. That is the bread-and-butter work of units like NICE. But the benefits may vary in ways that defy straightforward comparison. We need a common unit for measuring the goods achieved by health care. Since we are talking about comparing different goods, the choice of unit is not merely a scientific or economic question but an ethical one.

The costs of the current health care system are becoming increasingly clear, and public sentiment for a more systematic approach may be growing. We’d like to know what you think about the prospect of rationing.

As a first take, we might say that the good achieved by health care is the number of lives saved. But that is too crude. The death of a teenager is a greater tragedy than the death of an 85-year-old, and this should be reflected in our priorities. We can accommodate that difference by calculating the number of life-years saved, rather than simply the number of lives saved. If a teenager can be expected to live another 70 years, saving her life counts as a gain of 70 life-years, whereas if a person of 85 can be expected to live another 5 years, then saving the 85-year-old will count as a gain of only 5 life-years. That suggests that saving one teenager is equivalent to saving 14 85-year-olds. These are, of course, generic teenagers and generic 85-year-olds. It’s easy to say, “What if the teenager is a violent criminal and the 85-year-old is still working productively?” But just as emergency rooms should leave criminal justice to the courts and treat assailants and victims alike, so decisions about the allocation of health care resources should be kept separate from judgments about the moral character or social value of individuals.

Health care does more than save lives: it also reduces pain and suffering. How can we compare saving a person’s life with, say, making it possible for someone who was confined to bed to return to an active life? We can elicit people’s values on that too. One common method is to describe medical conditions to people — let’s say being a quadriplegic — and tell them that they can choose between 10 years in that condition or some smaller number of years without it. If most would prefer, say, 10 years as a quadriplegic to 4 years of nondisabled life, but would choose 6 years of nondisabled life over 10 with quadriplegia, but have difficulty deciding between 5 years of nondisabled life or 10 years with quadriplegia, then they are, in effect, assessing life with quadriplegia as half as good as nondisabled life. (These are hypothetical figures, chosen to keep the math simple, and not based on any actual surveys.) If that judgment represents a rough average across the population, we might conclude that restoring to nondisabled life two people who would otherwise be quadriplegics is equivalent in value to saving the life of one person, provided the life expectancies of all involved are similar.

This is the basis of the quality-adjusted life-year, or QALY, a unit designed to enable us to compare the benefits achieved by different forms of health care. The QALY has been used by economists working in health care for more than 30 years to compare the cost-effectiveness of a wide variety of medical procedures and, in some countries, as part of the process of deciding which medical treatments will be paid for with public money. If a reformed U.S. health care system explicitly accepted rationing, as I have argued it should, QALYs could play a similar role in the U.S.

Some will object that this discriminates against people with disabilities. If we return to the hypothetical assumption that a year with quadriplegia is valued at only half as much as a year without it, then a treatment that extends the lives of people without disabilities will be seen as providing twice the value of one that extends, for a similar period, the lives of quadriplegics. That clashes with the idea that all human lives are of equal value. The problem, however, does not lie with the concept of the quality-adjusted life-year, but with the judgment that, if faced with 10 years as a quadriplegic, one would prefer a shorter lifespan without a disability. Disability advocates might argue that such judgments, made by people without disabilities, merely reflect the ignorance and prejudice of people without disabilities when they think about people with disabilities. We should, they will very reasonably say, ask quadriplegics themselves to evaluate life with quadriplegia. If we do that, and we find that quadriplegics would not give up even one year of life as a quadriplegic in order to have their disability cured, then the QALY method does not justify giving preference to procedures that extend the lives of people without disabilities over procedures that extend the lives of people with disabilities.

The costs of the current health care system are becoming increasingly clear, and public sentiment for a more systematic approach may be growing. We’d like to know what you think about the prospect of rationing.

This method of preserving our belief that everyone has an equal right to life is, however, a double-edged sword. If life with quadriplegia is as good as life without it, there is no health benefit to be gained by curing it. That implication, no doubt, would have been vigorously rejected by someone like Christopher Reeve, who, after being paralyzed in an accident, campaigned for more research into ways of overcoming spinal-cord injuries. Disability advocates, it seems, are forced to choose between insisting that extending their lives is just as important as extending the lives of people without disabilities, and seeking public support for research into a cure for their condition.

The QALY tells us to do what brings about the greatest health benefit, irrespective of where that benefit falls. Usually, for a given quantity of resources, we will do more good if we help those who are worst off, because they have the greatest unmet needs. But occasionally some conditions will be both very severe and very expensive to treat. A QALY approach may then lead us to give priority to helping others who are not so badly off and whose conditions are less expensive to treat. I don’t find it unfair to give the same weight to the interests of those who are well off as we give to those who are much worse off, but if there is a social consensus that we should give priority to those who are worse off, we can modify the QALY approach so that it gives greater weight to benefits that accrue to those who are, on the QALY scale, worse off than others.

The QALY approach does not even try to measure the benefits that health care brings in addition to the improvement in health itself. Emotionally, we feel that the fact that Jack Rosser is the father of a young child makes a difference to the importance of extending his life, but his parental status is irrelevant to a QALY assessment of the health care gains that Sutent would bring him. Whether decisions about allocating health care resources should take such personal circumstances into account isn’t easy to decide. Not to do so makes the standard inflexible, but taking personal factors into account increases the scope for subjective — and prejudiced — judgments.

The QALY is not a perfect measure of the good obtained by health care, but its defenders can support it in the same way that Winston Churchill defended democracy as a form of government: it is the worst method of allocating health care, except for all the others. If it isn’t possible to provide everyone with all beneficial treatments, what better way do we have of deciding what treatments people should get than by comparing the QALYs gained with the expense of the treatments?

Will Americans allow their government, either directly or through an independent agency like NICE, to decide which treatments are sufficiently cost-effective to be provided at public expense and which are not? They might, under two conditions: first, that the option of private health insurance remains available, and second, that they are able to see, in their own pocket, the full cost of not rationing health care.

Rationing public health care limits free choice if private health insurance is prohibited. But many countries combine free national health insurance with optional private insurance. Australia, where I’ve spent most of my life and raised a family, is one. The U.S. could do something similar. This would mean extending Medicare to the entire population, irrespective of age, but without Medicare’s current policy that allows doctors wide latitude in prescribing treatments for eligible patients. Instead, Medicare for All, as we might call it, should refuse to pay where the cost per QALY is extremely high. (On the other hand, Medicare for All would not require more than a token copayment for drugs that are cost-effective.) The extension of Medicare could be financed by a small income-tax levy, for those who pay income tax — in Australia the levy is 1.5 percent of taxable income. (There’s an extra 1 percent surcharge for those with high incomes and no private insurance. Those who earn too little to pay income tax would be carried at no cost to themselves.) Those who want to be sure of receiving every treatment that their own privately chosen physicians recommend, regardless of cost, would be free to opt out of Medicare for All as long as they can demonstrate that they have sufficient private health insurance to avoid becoming a burden on the community if they fall ill. Alternatively, they might remain in Medicare for All but take out supplementary insurance for health care that Medicare for All does not cover. Every American will have a right to a good standard of health care, but no one will have a right to unrationed health care. Those who opt for unrationed health care will know exactly how much it costs them.

One final comment. It is common for opponents of health care rationing to point to Canada and Britain as examples of where we might end up if we get “socialized medicine.” On a blog on Fox News earlier this year, the conservative writer John Lott wrote, “Americans should ask Canadians and Brits — people who have long suffered from rationing — how happy they are with central government decisions on eliminating ‘unnecessary’ health care.” There is no particular reason that the United States should copy the British or Canadian forms of universal coverage, rather than one of the different arrangements that have developed in other industrialized nations, some of which may be better. But as it happens, last year the Gallup organization did ask Canadians and Brits, and people in many different countries, if they have confidence in “health care or medical systems” in their country. In Canada, 73 percent answered this question affirmatively. Coincidentally, an identical percentage of Britons gave the same answer. In the United States, despite spending much more, per person, on health care, the figure was only 56 percent.

Peter Singer is professor of bioethics at Princeton University. He is also laureate professor at the University of Melbourne, in Australia. His most recent book is “The Life You Can Save: Acting Now to End World Poverty.”

1.  whether receipt of posttrial services constitutes a fair benefit or an undue inducement to research participants,[1-4]
2. whether providing posttrial services unfairly prioritizes research participants over other community members,[5-7] and 
3. whether an obligation to provide such services creates an excessive burden for trial sponsors, thus reducing their incentive to conduct research.[5,6]

In addition, particularly for trials conducted in resource-limited settings, it has been suggested that local governments and nongovernmental organizations may be better suited than trial sponsors to provide posttrial services.^[7-9]

Limited survey data suggest that patients may have strong desires and expectations to receive posttrial services.

• 98% of participants in an international HIV trial stated that an efficacious study drug should be provided after trial conclusion to, at minimum, trial participants;
• 81% of these participants stated that the medication should be provided to all HIV-infected patients in the world.^[1]

In a second study, patients also felt that trial participants should receive lifelong medical care for both trial-related and -unrelated conditions.^[10] There is little published literature on expectations regarding posttrial services, or receipt of such services, for patients with conditions other than HIV infection.

Accurate expectations regarding posttrial services by research participants, investigators, and human subjects committee members may be particularly important for trials of antiretroviral drugs (ARVs) for HIV infection, given recent evidence of clinical risks following treatment interruption.^[11-13] However, providing long-term ARVs requires infrastructure, personnel, and clinical and laboratory monitoring that add substantial costs to the expense of ARVs alone and may not be available after trials conclude in resource-poor locations.^[6]

Despite the importance of posttrial services, international research guidelines offer few specific recommendations regarding these services.^[14-21] The Declaration of Helsinki asserts that posttrial access to interventions studied in trials should be “assured” to trial participants and that plans for posttrial services should be explicitly described in trial protocols.^[14] However, other widely cited research guidelines, including those of the US National Institutes of Health (NIH) Division of AIDS,^[15] state only that post-trial access to medications and medical care should be “considered” in the trial planning process.^[16-21]

Protocols and informed consent forms (ICFs) comprise important sources of information regarding trial procedures and trial-related benefits to participants, investigators, and human subjects committee members. Our objective was to characterize the ways in which posttrial services are described in protocols and ICFs of ARV clinical trials. We conducted a systematic review of trial protocols and template ICFs, and we report on the frequency with which these documents explicitly mention and/or offer to provide posttrial medications and medical care to trial participants.

Method

Clinical Trials Included

We identified all eligible Phase 3 and Phase 4 ARV trials in adults, sponsored by either the pharmaceutical industry or the NIH. Phase 3 trials were included to capture investigational medications with a high probability of demonstrating efficacy but not yet commercially available, thereby creating a situation in which they would be desired by participants after trial completion. Phase 4 trials were included to evaluate situations in which patients might be expected to have another means of obtaining the study medication after trial completion, for example by prescription through their usual means of obtaining medical care.^[22]

We used different methods to identify three types of trials. Industry-sponsored Phase 3 trials were identified from US Food and Drug Administration (FDA) drug approval documentation records.^[23] Industry-sponsored Phase 4 trials were identified from the international Clinicaltrials.gov registry maintained by the NIH.^[24] NIH-sponsored trials were limited to those administered through the adult AIDS Clinical Trials Group (ACTG), the largest NIH-sponsored HIV trials network, and were identified from the ACTG protocol-specific Web pages.^[25] Trials were selected according to the following inclusion and exclusion criteria ( Table 1 ).

All Trials. For all categories of trials, we included stand-alone studies of ARV trials in adults (≥12 years old) conducted during or after 1987 (the year in which zidovudine was approved for treatment of HIV). The analysis was limited to trials completed by December 13, 2006 to improve the willingness of pharmaceutical companies to share confidential trial documents.

Phase 3 Trials. Industry-sponsored Phase 3 trials were limited to all trials identified as the “pivotal” trials leading to FDA approval of single-formulation HIV medications for adults. The FDA Center for Drug Evaluation and Research (CDER) documents the licensing process for all approved HIV medications and designates specific Phase 3 trials as the “pivotal” sources of data used for approval.^[23] Pivotal trials were chosen to create a reasonably sized sample of industry-sponsored trials that spanned nearly 20 years, both before and after introduction of highly active antiretroviral therapy. In addition, all ACTG-administered Phase 3 trials were included.^[25]

Phase 4 Trials. All industry-sponsored Phase 4 ARV trials registered on Clinicaltrials.gov were included.^[24] All ACTG-administered Phase 4 trials were included.

Document Procurement and Data Extraction

We attempted to obtain the protocols and ICFs of all eligible trials. Protocols and ICFs for industry-sponsored trials were obtained by direct request from the sponsoring pharmaceutical companies. Confidentiality agreements were executed between the investigators and all pharmaceutical companies requesting such documentation, ensuring that drugs and trials would be de-identified in all reports. Although we attempted to obtain documents for all remaining trials from the FDA via the Freedom of Information Act, these documents are proprietary and are not subject to this Act (CDER, e-mail communication, Nov. 2, 2006). ACTG protocols and template ICFs were provided by ACTG staff. This research was approved by the Human Subjects Committee of the Massachusetts General Hospital.

Only trials for which complete protocols and ICFs were available by July 1, 2008 (18 months after study initiation) were included. All protocols, appendices, amendments, and template ICFs were reviewed in full by the first author. Missing data were obtained from the ACTG Website and Clinicaltrials.gov when available.

Trial Characteristics and Services Provided to Participants During Trial Periods

Data were collected regarding the date and version number of the last available protocol/amendment, location of trial sites (United States, other developed setting, or resource-limited setting), sponsorship (industry or NIH [ACTG]), anticipated number of participants, age and gender inclusion criteria, and trial duration. Data were also collected regarding additional services offered to participants during the trial period. These included on-study provision of the study drug itself, other required ARVs (”background regimen”), and substitute drugs (as needed for drug toxicity or virologic failure). We also recorded mention or offer of payment for study participation (worded as “payment,” “compensation,” or “reimbursement,” including offers to compensate subjects for time, transportation costs, or child care costs), and mention or offer of payment for care for trial-related injury. These variables were recorded as comparators for services offered after trial conclusion and in order to test a priori hypotheses regarding trial characteristics associated with the primary and secondary outcomes.

Outcomes

The clinical trial was the unit of analysis. The primary outcome was any mention of posttrial services, defined as any text regarding medications or medical care following trial conclusion. Amendments extending the duration of previously enrolled trials met this definition only if they referred to services to be provided after the conclusion of the last described trial phase.

Associations between trial characteristics and the primary outcome were examined using chi-square exact tests with an alpha level of 0.05 (SAS 9.1; SAS Institute, Cary, North Carolina, USA). Multivariate analyses were planned but were precluded by the small sample size. We hypothesized that posttrial services would more frequently be mentioned in the documents of (a) trials with protocols written after 2000 (compared to those written before 2000), reflecting increased awareness of international research ethics guidelines; (b) Phase 3 trials (compared to Phase 4 trials), reflecting a finite period of anticipated need for medications between trial completion and drug licensure; (c) pharmaceutical industry-sponsored trials (compared to NIH/ ACTG-sponsored trials), reflecting greater financial resources for provision of posttrial services and 2005 NIH guidelines stating that posttrial medications would not be supplied;^[15] (d) trials conducted in developed settings (compared to those conducted in resource-limited settings), reflecting lower levels of anticipated need for posttrial services due to private or public insurance; and (e) trials offering to provide payment for participation or care for trial-related injury during the trial periods (compared to trials not offering such services), reflecting a greater overall willingness to provide services to participants.

For trial documents in which posttrial services were mentioned, secondary outcomes included whether trial documents offered to provide medications or offered to provide medical care to participants after trial completion. If posttrial medications or medical care were offered, information was extracted regarding (a) the type of medications or care offered, (b) which participants were eligible to receive these services, (c) the duration for which these services were offered, and (d) who was to pay for medications or care.

Results

Trial Characteristics and Services Provided to Participants During Trial Periods

Sixty-five trials met criteria for inclusion; documents from 31 of the 65 eligible trials were obtained. Reasons for lack of availability of the remaining documents are detailed in Table 2 . Trials ranged widely in number of participants (range, 30-3236; median = 325) and in duration (range, 16-416 weeks; median = 103 weeks) ( Table 3 ). On average, ACTG-administered trials occurred earlier (1987-2004) than industry-sponsored trials (1996-2005). Fifty-eight percent of trials were conducted entirely within the United States, and only two trials (6%) were conducted entirely in resource-limited settings (one each in South Africa and Brazil).

Provision of Antiretroviral Drugs. During the trial periods, all but one trial offered all necessary study drugs to participants ( Table 4 ). In 16 trials (52%), additional “background” ARVs were required; 6 trials (19%) required participants to obtain these medications from sources outside of the study, 9 trials (29%) provided background ARVs completely or partially, and 1 trial (3%) did not specify whether background ARVs would be provided. In the event of virologic failure or toxicity requiring substitutions in study drug or background ARVs, three trials (10%) provided any needed substitute ARV; eight trials (26%) provided selected substitute ARVs only; and four trials (13%) stated that substitute ARVs were permitted but not provided. In 15 trials (48%), no substitute ARVs were available, primarily because a need for substitution necessitated study discontinuation.

Mention of Payment for Study Participation. Documents from 23 trials (74%) explicitly mentioned whether participants would be paid for trial participation ( Table 4 ). Eight trials (26% of total trials) specified that participants would be paid, and trials (48% of total trials) stated that participants would not be paid.

Mention of Payment for Care for Trial-related Injury. Documents from 29 trials (94%) explicitly mentioned whether participants would receive reimbursement for care for any trial-related injury ( Table 4 ). Seventeen of these (55% of total trials) stated that injury care would be reimbursed, and trials (39% of total trials) stated that such care would not be reimbursed.

Mention and Offer of Posttrial Services

Mention of Posttrial Services. Posttrial services of any type were mentioned in the documents of 14 trials (45% of trials, 54% participants; Table 5 ). Documents from 12 trials (39% of trials, 44% of participants) mentioned posttrial medications. Documents from five trials (16% of trials, 28% of participants) mentioned posttrial medical care. Not mentioning or providing payment to participants, as well as anticipated enrollment greater than the median, were significantly associated with mentioning any posttrial service and with mentioning posttrial medications ( Table 6 ). Enrollment greater than the median, trial sponsor (NIH/ACTG), and not offering payment for injury care (a characteristic of all ACTG trials) were significant correlates of mentioning posttrial medical care.

Offer to Provide Posttrial Medications. Of the 12 trials mentioning posttrial medications, 10 offered to provide medications after trial conclusion (32% of trials, 34% of participants), and 2 stated that posttrial medications would not be provided (6% of trials, 9% of participants). Not mentioning or providing payment to participants, anticipated enrollment greater than the median, and inclusion of at least one trial site in a resource-limited setting were significantly associated with offering to provide posttrial medications. Of the 10 trials offering to provide posttrial medications, 7 were industry-sponsored trials. Seven offered study drug, and one offered study drug with background ARVs. Six trials offered posttrial medications to all study completers; two offered posttrial medications only to participants completing the study drug arm. Two additional trials offered the “best available alternative treatment” after trial conclusion (one of these at participant expense), although this was limited to participants failing zidovudine in the late 1980s, when few alternative HIV therapies were available. Six trials offered posttrial medications until commercial availability or for a defined period thereafter, one until a rollover protocol enrolled, and three for an unspecified duration. Posttrial medications were offered at sponsor expense in eight trials, at participant expense in one trial, and without specified payer in one trial.

Offer to Provide Posttrial Medical Care. Of the five trials mentioning posttrial care, one (3% of trials, 2% of participants) offered to provide posttrial medical care. This was further explained as the “best available care” for participants failing zidovudine in the late 1980s, offered at participant expense. In the remaining four trials (13% of trials, 26% of participants), documents stated that post-trial care would not be provided.

Trial Characteristics Not Associated with Primary Outcomes

Calendar year of trial documents was not associated with mention of any posttrial service or offer of posttrial medications; 42% of documents from trial documents written before 2000 and 47% of trial documents written after 2000 mentioned any posttrial service (p = 1.0). In addition, trial phase (Phase 3 compared to 4), trial duration, age inclusion criteria, and provision of background or substitute ARVs were not associated with mentioning any posttrial service or with offering posttrial care. Because only one trial offered posttrial medical care, bivariate analysis was not performed for this outcome. The small number of trials reviewed precluded multivariate analysis of the associations between trial characteristics and mention or offer of posttrial services.

Discussion

Accurate expectations regarding access to medications and medical care after clinical trial conclusion are crucial to informed decision making by research participants, investigators, and human subjects committee members. This may be particularly true in the case of trials of antiretroviral drugs for HIV infection, after which participants who lack access to effective, combination ARVs may experience clinical deterioration.^[11-13] To our knowledge, this study represents the first published review of descriptions of posttrial services in clinical trial documents.

In this sample of major Phase 3 and 4 ARV trials, posttrial medications and medical care were mentioned in the protocols or ICFs of fewer than half (45%) of all trials. Plans regarding payment for trial participation (74%) and payment for care for trial-related injury (94%) were explicitly mentioned more often than were posttrial services, suggesting that authors and reviewers of trial documents are more aware of the importance of describing services offered during trial periods than of the need to outline plans for posttrial services. Post-trial services were mentioned in documents from 12 trials, and 10 (70%) of these offered to provide posttrial medications. Of these 10 trials, 70% were industry-sponsored trials, 60% offered medications until they became commercially available, and 80% offered medications at sponsor expense, reflecting current diversity of recommendations and interpretations about posttrial services.

Decisions about whether posttrial services should be provided are complex, because they include discrete and heavily debated questions about what services should be provided (study medications, other medications, or medical care),^[1,10] to whom they should be provided (all study completers, or other community members),^[1,26,27] and for how long they should be provided (until medications become commercially available, or indefinitely).^[10] Several authors have suggested that trial sponsors should assume at least some responsibility for providing posttrial services.^[5,6,16,28] Important roles for investigators, local organizations, and national governments have also been proposed,^[6,7,15,28] with or without sponsor financial support to create enduring local health care capacity.^[9] The extent of sponsor obligation may depend on whether the sponsor is a government agency or a for-profit entity, which might be expected to have greater financial capacity to provide posttrial services.^[27] In support of this concept, the NIH Division of AIDS states that “the NIH’s authority to ‘encourage and support research’ does not extend to providing treatment following the completion of that research.”^[15]

We found no association between mention or offer of posttrial services and the year in which trial documents were written (before or after 2000), although our study had limited power to detect such effects. Although research guidelines began to mention posttrial services in the 1990s,^[16,21,27] the Declaration of Helsinki (2000, revised 2004) was the first such guideline to clearly recommend that posttrial services be mentioned in trial protocols.^[14] Many of the trials included in this review predate these recommendations; however, our limited data suggest that the proportion of trials in which documents mention posttrial services does not appear to have substantially increased after the year 2000. In 2005, the NIH issued guidelines (quoted above) for trials conducted in resource-limited settings, asserting that NIH would not provide posttrial medications and recommending instead that “investigators engage in a dialogue with host countries’ authorities . . . in order to facilitate the inclusion of [ARV trial participants] in available in-country antiretroviral treatment programs.” These guidelines may have increased mention of post-trial services in trial documents; but, by insisting that NIH not provide posttrial medications, they may also have reduced offers of posttrial medications. Documents for the ACTG trials meeting our inclusion criteria were written in 2004 or earlier, and only one was conducted in a resource-limited setting, so these studies were not subject to the 2005 NIH guidelines.

Because of the small numbers of ACTG trials meeting our inclusion criteria, the low proportion of trials provided by pharmaceutical sponsors, and the large number of statistical comparisons made, our conclusions regarding the associations between trial characteristics and mention or offer of posttrial services must be interpreted only as hypothesis-generating. The direction of several statistically significant associations was contrary to what had been hypothesized, for example, mentioning or offering posttrial services was associated with “not mentioning” or “not providing” payment for trial participation, whereas we hypothesized that mentioning or providing payment would suggest a greater overall level of services provided and would be associated with these outcomes. This suggests that other trial factors may explain this association. Similarly, the observed association between not providing injury-related care and mentioning posttrial medical care is explained by a statement common to more recent ACTG trials (1997-2004), specifying that pediatric and pregnancy-related care would not be provided if participants became pregnant during the studies. Numbers of included trials were too small to permit multivariate analysis to further explore these relationships.

Major international research ethics guidelines do not provide specific guidance to researchers regarding posttrial services.^{[14,16,17,19-21]} It is likely that no single recommendation about posttrial services will be appropriate to all research situations, because the specific risks to participants and needs of the communities in which research is conducted will differ between trials.^[2] Instead, it may be helpful to outline a process by which posttrial services can be included among the other risks and benefits considered in the standardized evaluation of all proposed trials.^[2] For example, education regarding posttrial services could be a component of the training required for a Federal-Wide Assurance (FWA) number for human subjects committees.^[29] Additionally, a description of “planned post-trial services” could be added as a required component of trial protocols and ICFs. This might involve a requirement similar to that currently in place for trials that are subject to FDA requirements and that involve at least minimal risk to subjects: ICFs for such trials must include clear descriptions of plans regarding payment for care for trial-related injury, regardless of whether or not such payment will be provided.^[9,14,30]

During the protocol development process, sponsors may be appropriately reluctant to commit to a future obligation to provide posttrial services, due to uncertainty about drug efficacy or about future financial circumstances.^[18,19,31] However, given the very high expectations of some surveyed trial participants,^[1,10] a statement about posttrial services, even one that makes explicit that posttrial services are not guaranteed, may help to ensure that unreasonable expectations do not play a role in decisions about trial participation.

This study has several important limitations. First, documents other than protocols and ICFs (including internal memoranda, sponsor/investigator contracts, and local ICFs) may contain information about posttrial services and were not reviewed in this study. However, with the exception of local ICFs, these additional documents are likely to be less readily available to participants, investigators, and site human subjects committee members than the protocols and template ICFs. Second, we reviewed all available versions of protocols and ICFs, and the definition of “mention of post-trial services” was fulfilled only if such mention referred to the time after the trial period described in that document version was to conclude. Although this definition may incompletely capture the practice in which trial sponsors provide posttrial services through amendments that extend trials until drugs become commercially available, it is consistent with the goal of making planned posttrial services explicit at the time of participant recruitment.

Finally, the eligible sample of 65 ARV trials included only pivotal industry-sponsored Phase 3 trials leading to medication licensure, rather than a complete sample of Phase 3 ARV trials, and included only ACTG-administered trials, rather than all NIH-sponsored trials. Furthermore, the obtained sample included fewer than half of the eligible trials (93% of ACTG trials, but only 34% of industry-sponsored trials).

This sample of reviewed trials may be biased for two reasons. First, the inclusion of only “pivotal” Phase 3 industry-sponsored trials (those leading to medication approval) resulted in a sample of trials of efficacious medications, after which sponsors may be more likely to offer medications than after trials of inefficacious medications. Second, sponsors may have been less willing to share eligible trial documents in which posttrial services were not mentioned. If documents from all 34 unavailable trials did not mention posttrial services, then the total proportion of trials mentioning post services could be as low as 14 of 65 (22%) overall: 47% (7/15) of ACTG studies and 14% (7/50) of industry studies. Both sources of bias would be expected to lead to results indicating that posttrial services are mentioned or offered more frequently than is really the case. Although clearly important limitations of our study, these factors may suggest that the low frequencies of the outcomes that we observed are even more worthy of consideration.

We are aware of no reports of actual rates of receipt of posttrial services by trial participants with HIV infection or other medical conditions. Efforts to characterize trial participants’ expectations regarding posttrial services and their actual rates of receipt of such services remain important directions for future research. In the meantime, trial sponsors should explicitly communicate their plans about posttrial services to trial participants, investigators, and human subjects committees at the time of protocol approval and participant recruitment, whether or not they intend to provide such services. This could be accomplished by including clear descriptions of plans for posttrial services in trial protocols and informed consent forms. This review suggests that such explicit statements are not yet the standard practice in major HIV clinical trials.

The case was brought on behalf of a 13-year-old girl with fragile X syndrome, a common inherited form of mental retardation.

While the judge dismissed several claims, he allowed others to move forward; the WSJ’s Law Blog hashes out the legal details.

One interesting legal/medical issue is the way state laws differ — the law in New York, where the sperm bank is located, state law provides companies that traffic in human tissue and the like less protection than a similar law in Pennsylvania, where the girl was conceived.

A case report on the girl was published last year in the American Journal of Genetics Part A.

“We suggest fragile X DNA screening in gamete donor candidates to decrease the chance of fragile X involvement in their offspring,” the authors wrote.

Thompson, after all, exercises body and mind daily, even developing his own workout program for seniors that emphasizes stretching, deep breathing, light aerobics and modified sit-ups and push-ups. And, six months ago, he recovered from invasive bladder and prostate cancer surgery quicker than some patients half his age.

“He is a fairly remarkable individual,” says Thompson’s urologist, Dr. Ralph deVere White, director of the University of California-Davis Cancer Center. Remarkable, yes. But not an anomaly.

Doctors, who traditionally have been hesitant to perform major surgery on patients age 80 or older, are beginning to revise the standard of care. More and more, patients inching toward the century mark are undergoing cancer operations, open-heart surgery and joint replacements at an age when previously they might have been told to take it easy and let nature take its course.

Credit improvements in medical technology, coupled with a fast-growing aging population skewing healthier than previous generations, for the shift.

But such advances have not arrived without controversy in the medical community. Much of the concern deals with bioethics issues such as quality-vs.-quantity of life and the growing monetary burden on Medicare. There also is the specter of ageism. To wit: Is it appropriate to put a shelf life on procedures based on a patient’s chronological age? Far from an academic discussion, this situation was all too real for Thompson.

Thompson, of Roseville, was diagnosed a year ago with bladder cancer, the fourth-most-common cancer among American men. He said his original doctor took what charitably could be called the conservative, wait-and-see approach. Surgery was not considered. Chemotherapy was discouraged. Thompson considered it like throwing in the towel before even starting the fight.

“It was the wrong approach for someone like me,” he says. Too stubborn, not too old, Thompson sought another opinion.

That led him to deVere White, the UC-Davis urologist who coincidentally had just concluded a research study with colleague Dr. Karim Chamie showing that otherwise healthy octogenarians can tolerate invasive surgery — radical cystectomy, to be precise — to treat bladder cancer.

The study, published in August in the British Journal of Urology International, showed as much as a 52-months-of-life benefit for many elderly who had surgery, provided they did not die from an unrelated disease. But the overall survival rate for all octogenarian bladder cancer patients differed only slightly (18 months to 15 months) for those who had surgery compared to radiotherapy.

“I think you could absolutely argue that putting anyone through the surgery and recovery for three months of extra life when you’re 80 years old is not worth it for the patient,” deVere White says. “On the other hand, if you look at the patients who had the surgery and got their lymph nodes (removed) and did not die of some other disease, then you’re looking at over four years of extra life. That, I think, is worth it.”

After Thompson had three rounds of chemotherapy that failed to help his condition, deVere White recommended surgery.

It was not a decision he made lightly.

“A lot of doctors still feel hesitant (to operate),” deVere White says. “And there’s no doubt that a patient’s comorbities (other risks) clearly play a big factor. Life is finite. Obviously, as you get to some age, the threshold becomes quality of life being maybe more important than quantity.

“I think this has been interpreted by a number of people as, ‘OK, we really shouldn’t be operating on octogenarians.’ The first I read about this was a few years ago from the public health school at Harvard. They said an awfully lot of elderly people appear to be undertreated and you really cannot generalize about age.”

Thompson didn’t have to be persuaded. He wanted the surgery.

“It’s the right thing to do and let’s do it now,” he told deVere White.

In June, he had the operation to remove his bladder, 13 pelvic lymph nodes and related urinary organs. DeVere White ended up removing Thompson’s cancer-ridden prostate.

Thompson was told he would need a 10-day postoperative hospital stay. He made it out in four. For heart patients, surgery to replace valves or perform angioplasty no longer is rare, says Dr. Robert Kincade, cardiac surgeon with the Sutter Heart & Vascular Institute in Sacramento.

“There’s been a shift toward older patients, because people are living longer and staying healthier longer,” he says. “And there are new techniques that make surgery safer.”

But …

“We don’t operate on everybody in their 80s who needs surgery,” Kinkade says. “Sometimes the thing to do is not operate on them. In general, we look at their overall health and physical condition.” This is where the ethical concerns come in. Just because you can prolong an elderly patient’s life, should you?

“There’s no question that at some point the issue of who’s going to pay for this has to come into it,” says Dr. Ben Rich, the endowed chair of bioethics at UC-Davis Medical School. “Nobody’s saying this kind of allocation decision based largely or entirely on age is something that should be done at the bedside. It should be done as a matter of public policy.”

Among the longtime advocates of rationing health care for the elderly to ease the burden on Medicare is Dr. Daniel Callahan, co-founder of the Hastings Center, a bioethics think tank in New York.

Callahan once suggested that, to save Medicare, patients over 80 should not have invasive surgeries. Such a stance has proven controversial, especially considering that the Census Bureau reports that 85-plus is the fastest-growing age demographic in the United States.

In a recent essay on a New York Times health blog, Callahan wrote, “Doctors endlessly complain to me that excessive patient expectations of medical miracles, or those of their family members, make it harder, not easier, these days to curtail aggressive treatment.”

He later added: “There’s nothing we can’t do for an older person, and there’s a lot of pressure to do it. This is considered progress, and it’s considered ageism to be skeptical.”

Geriatrician Dr. Michael McCloud of UC Davis is adamant that there should be no age limit for surgery.

“Should I have the misfortune of breaking my hip while dancing at my 100th birthday party, and should my doctor advise that I am too old for surgical repair, I will replace doctors as quickly as I replace that hip,” he says.
http://www.montereyherald.com/ci_11579898?source=rss

Ms. Miller’s panel entitled, “Climate Justice Adaptation: Public Health and Emergency Preparedness,” is schedule for this Thursday January 29th at 1:15pm.  We look forward to seeing you Thursday. 

• Panel Time: Thursday January 29, 2009 1:15pm – 2:30pm
• Location: Fordham University Lincoln Center Campus, 113 W. 60th St., New York City
• Panelists’ Bios
• Conference Agenda
• Panel Description: Emergency preparedness for climate disasters is an increasingly essential and immediate element of climate change adaptation. Panelists will examine how municipalities are preparing for imminent climate disasters and the need to protect communities from displacement, disinvestments and disempowerment in the immediate aftermath of climate disasters.