[FirstWord] Merck & Co. disclosed Monday in an SEC filing that it received a subpoena from the US Department of Justice as part of a “federal health care investigation under criminal statutes” into the company’s marketing of three drugs acquired in its merger with Schering-Plough. Merck spokesman Ron Rogers said the drugmaker is cooperating with the probe.

Specifically, the agency requested information from January 2004 to the present on the brain cancer drug Temodar (temozolomide), hepatitis C therapy PegIntron (pegylated interferon alfa-2b), and Intron A (interferon alfa-2b), which is approved for the treatment of certain cancers and other conditions. Sales of the drugs totalled $481 million, $319 million and $96 million, respectively, in the first six months of this year.

Separately, Merck revealed that the justice department and Environmental Protection Agency (EPA) are pursuing civil penalties of more than $2 million against the company for alleged violations of environmental regulations at two Pennsylvania facilities. The action results from the EPA’s inspection of the West Point and Riverside sites in 2006, and Merck’s submission of information to the agency. However, the drugmaker indicated that it believes it has meritorious defences against the allegations.

In addition, Merck said that it agreed to pay a $260 000 fine and sign a consent decree to resolve alleged environmental violations at its Las Piedras facility in Puerto Rico in connection with an EPA inspection in 2008.

[Bloomberg] Teva Pharmaceutical Industries Ltd. (TEVA), the world’s largest generic-drug maker, was sued by a joint venture of GlaxoSmithKline Plc (GSK) and Pfizer Inc. (PFE) for infringing a U.S. patent for the HIV drug Epzicom.

Teva has applied to the U.S. Food and Drug Administration for permission to sell generic Epzicom tablets in violation of a 2002 patent, lawyers for ViiV Healthcare said in an Aug. 5 complaint filed in federal court in Wilmington, Delaware.

Teva’s FDA submission “constitutes infringement” and “ViiV will be irreparably harmed” by the low-cost version of Epzicom if it’s sold before the patent expires in 2016, according to court papers.

GlaxoSmithKline, based in Brentford, England, and New York- based Pfizer announced the ViiV joint venture to combat HIV in 2009. The lawsuit seeks a permanent injunction to block Israel- based Teva’s U.S. sales of the drug and damages if the generic medicine is sold.

ViiV has facilities in Brentford and at Research Triangle Park in North Carolina, according to court papers.

Teva spokeswoman Denise Bradley declined to comment on the suit

The case is ViiV Healthcare UK Ltd. v. Teva Pharmaceuticals USA Inc., U.S. District Court for the District of Delaware (Wilmington).

This could be changing, however. The pharmaceutical industry has persuaded several governments to stiffen regulations against fake drugs and to conduct more aggressive raids (see chart). Companies are also devising novel technologies to outfox the criminals. Even the Catholic church is joining the cause, issuing a stern statement in August that it is in “the best interest of all concerned that smuggling of counterfeit drugs be fought against”.

The pope’s concern is justified. Counterfeit drugs can kill. Many are shoddily made, containing the wrong dose of the active ingredient. Taking them instead of the real thing can turn a treatable disease into a fatal one. It can also foster drug resistance among germs. This has been a big problem for a long time in developing countries. Studies of anti-infective treatments in Africa and South-East Asia have found that perhaps 15-30% are fakes. The UN estimates that roughly half of the anti-malarial drugs sold in Africa—worth some $438m a year—are counterfeits.

Roger Bate of the American Enterprise Institute, a think-tank in Washington, DC, cautions that any such estimates should be treated with care. The countries with the most fakes may not be cracking down, so official figures will look rosy; in contrast, countries with a smaller counterfeit trade that are vigilant may end up with more seizures. The World Health Organisation agrees, and has recently taken its estimates off its website. Even so, Mr Bate says his field work has convinced him that counterfeits kill at least 100,000 people a year, mostly in the poor world.

Now it appears that fakes are taking off in the rich world too. Yes, Viagra still tops the list of knock-offs seen by Pfizer, says John Clark, the American drug firm’s global head of security; but fake versions of at least 20 of its products (including Lipitor, a blockbuster cholesterol drug) have been detected in the legitimate supply chains of at least 44 countries. Mr Clark’s intelligence comes from Pfizer’s global network of informants, consumer tip-offs and in-store inspections. He sees worrying trends.

Counterfeiters used to operate chiefly in developing countries, says Mr Clark, but now his firm sees fakes coming from such rich and well-regulated places as Canada and Britain. And the crooks are growing more technologically sophisticated: some can even counterfeit the holograms on packets that are meant to reassure customers that pills are genuine.

A consumer study funded by Pfizer recently found that nearly a fifth of Europeans polled in 14 countries had obtained medicines through illicit channels. That, the firm reckons, makes for a grey market in the EU of over €10 billion ($12.8 billion). Terry Hisey of Deloitte, a consultancy, thinks the global market for fakes could be worth between $75 billion and $200 billion a year. Those staggering sums, he argues, help explain the emergence of a flurry of new technologies and companies hoping to help the drugs industry “secure its global supply chain”.

In July Oracle, an American software giant, unveiled Pedigree, a programme that helps drugs firms “track and trace” pills all the way from the factory to your fingers. IBM has a rival offering, as well as one using radio-frequency identification (RfID) chips, which are embedded in packaging to detect tampering and allow precise tracking. 3M, a materials company, and Abbott Laboratories, an American medical firm, are also rolling out an RfID-based product. A division of Johnson & Johnson, a drugs giant, has developed web-based software to help customs officials quickly verify whether drugs are fake or real.

Poor countries find it hard to take advantage of such technologies. Sophisticated radio tags and database software are not much use in places where street hawkers peddle fakes with impunity. Still, even in such difficult circumstances, a combination of political will and business ingenuity can make a difference.

Bottom-up battle

A Ghanaian start-up firm, mPedigree, has come up with a clever way to use mobile phones in this fight. Participating drugs companies emboss a special code onto packages, which customers find by scratching off a coating. By sending a free text with that code, they can find out instantly if the package is genuine or a fake.

Bright Simons, the firm’s boss, argues that technologies like his can be a useful bottom-up complement to top-down enforcement. Having successfully completed initial trials, he says, mPedigree is ready to expand its service in the region. The government of Nigeria, where fakery is rife, recently declared its intention to adopt such a text-based validation system.

Thomas Kubic of the Pharmaceutical Security Institute, an industry-funded outfit, gives warning that this war will be hard to win. After more than 30 years as an investigator, he is sure that crooks will eventually find a way around any defence.

Even so, he thinks novel approaches such as mobile-based validation may “harden the target”, just as a burglar alarm makes your home somewhat trickier to rob. If the cost and complexity of faking drugs goes up, crooks may choose to fake Gucci handbags instead. This would still be theft, not to mention a crime against fashion. But it will not kill anyone.

While the findings may seem obvious, health economists and policy makers have long questioned whether it would make any difference to provide health insurance to poor people.

It has become part of the debate on Medicaid, at a time when states are cutting back on this insurance program for the poor. In fact, the only reason the study could be done was that Oregon was running out of money and had to choose some people to get insurance and exclude others, providing groups for comparison.

Some said that of course it would help to insure the uninsured. Others said maybe not. There was already a safety net: emergency rooms, charity care, free clinics and the option to go to a doctor and simply not pay the bill. And in any case, the argument goes, if Medicaid coverage is expanded, people will still have trouble seeing a doctor because so few accept that insurance.

Until now, the arguments were pretty much irresolvable. Researchers compared people who happened to have insurance with those who did not have it. But those who do not have insurance tend to be different in many ways from people who have it. They tend to be less educated and to have worse health habits and lower incomes, said Dr. Alan M. Garber, an internist and health economist at Stanford. No matter how carefully researchers try to correct for the differences “they cannot be completely successful,” Dr. Garber said. “There is always some doubt.”

The new study, published Thursday by the National Bureau of Economic Research, avoided that problem. Its design is like that used to test new drugs. People were randomly selected to have Medicaid or not, and researchers then asked if the insurance made any difference.

Health economists and other researchers said the study was historic and would be cited for years to come, shaping health care debates.

“It’s obviously a really important paper,” said James Smith, an economist at the RAND Corporation. “It is going to be a classic.”

Richard M. Suzman, director of the behavioral and social research program at the National Institute on Aging, a major source of financing for the research, said it was “one of the most important studies that our division has funded since I’ve been at the N.I.A.,” a period of more than a quarter-century.

In its first year of data collection, the study found a long list of differences between the insured and uninsured, adding up to an extra 25 percent in medical expenditures for the insured.

Those with Medicaid were 35 percent more likely to go to a clinic or see a doctor, 15 percent more likely to use prescription drugs and 30 percent more likely to be admitted to a hospital. Researchers were unable to detect a change in emergency room use.

Women with insurance were 60 percent more likely to have mammograms, and those with insurance were 20 percent more likely to have their cholesterol checked. They were 70 percent more likely to have a particular clinic or office for medical care and 55 percent more likely to have a doctor whom they usually saw.

The insured also felt better: the likelihood that they said their health was good or excellent increased by 25 percent, and they were 40 percent less likely to say that their health had worsened in the past year than those without insurance.

The study is now in its next phase, an assessment of the health effects of having insurance. The researchers interviewed 12,000 people — 6,000 who received Medicaid and 6,000 who did not — and measured things like blood pressure, cholesterol and weight.

The study became possible because of an unusual situation in Oregon. In 2008, the state wanted to expand its Medicaid program to include more uninsured people but could afford to add only 10,000 to its rolls. Yet nearly 90,000 applied. Oregon decided to select the 10,000 by lottery.

Economists were electrified. Here was their chance to compare those who got insurance with those who were randomly assigned to go without it. No one had ever done anything like that before, in part because it would be considered unethical to devise a study that would explicitly deny some people coverage while giving it to others.

But this situation was perfect for assessing the impact of Medicaid, said Katherine Baicker, professor of health economics at the Harvard School of Public Health. Dr. Baicker and Amy Finkelstein, professor of economics at M.I.T., are the principal investigators for the study.

“Amy and I stumbled across the lottery in Oregon and thought, ‘This is an unbelievable opportunity to actually find out once and for all what expanding public health insurance does,’ ” Dr. Baicker said.

They had just a short window of time. Within two years, Oregon found the money to offer Medicaid to the nearly 80,000 who had been turned down in the lottery.

As an economist, Dr. Finkelstein was interested, among other things, in whether Medicaid did what all insurance — homeowner’s, auto, health — is supposed to do: shield people from financial catastrophe. Almost no one had even tried to investigate that question, she said.

“It is shocking that it is not even in the discourse,” Dr. Finkelstein said.

The study found that those with insurance were 25 percent less likely to have an unpaid bill sent to a collection agency and were 40 percent less likely to borrow money or fail to pay other bills because they had to pay medical bills.

Dr. Finkelstein said she had thought that the people were so poor to begin with that they just did not spend very much out of pocket on medical care when they did not have insurance. “Yet look at the results,” she said.

Dr. Baicker interviewed people for Part 2 of the study and was impressed by what she heard.

“Being uninsured is incredibly stressful from a financial perspective, a psychological perspective, a physical perspective,” she said. “It is a huge relief to people not to have to worry about it day in and day out.”

Doctors would assess her tumor cells, looking for gene patterns that would determine which drugs would best attack her particular cancer. She would not waste precious time with ineffective drugs or trial-and-error treatment. The Duke program — considered a breakthrough at the time — was the first fruit of the new genomics, a way of letting a cancer cell’s own genes reveal the cancer’s weaknesses.

But the research at Duke turned out to be wrong. Its gene-based tests proved worthless, and the research behind them was discredited. Ms. Jacobs died a few months after treatment, and her husband and other patients’ relatives are suing Duke.

The episode is a stark illustration of serious problems in a field in which the medical community has placed great hope: using patterns from large groups of genes or other molecules to improve the detection and treatment of cancer. Companies have been formed and products have been introduced that claim to use genetics in this way, but assertions have turned out to be unfounded. While researchers agree there is great promise in this science, it has yet to yield many reliable methods for diagnosing cancer or identifying the best treatment.

Instead, as patients and their doctors try to make critical decisions about serious illnesses, they may be getting worthless information that is based on bad science. The scientific world is concerned enough that two prominent groups, the National Cancer Institute and the Institute of Medicine, have begun examining the Duke case; they hope to find new ways to evaluate claims based on emerging and complex analyses of patterns of genes and other molecules.

So far, the Food and Drug Administration “has generally not enforced” its regulation of tests created by individual labs because, until recently, such tests were relatively simple and relied heavily on the expertise of a particular doctor, said Erica Jefferson, a spokeswoman for the agency. But now, with labs offering more complex tests on a large scale, the F.D.A. is taking a new look at enforcement.

Dr. Scott Ramsey, director of cancer outcomes research at the Fred Hutchison Cancer Center in Seattle, says there is already “a mini-gold rush” of companies trying to market tests based on the new techniques, at a time when good science has not caught up with the financial push. “That’s the scariest part of all,” Dr. Ramsey said.

Doctors say the heart of the problem is the intricacy of the analyses in this emerging field and the difficulty in finding errors. Even well-respected scientists often “oversee a machine they do not understand and cannot supervise directly” because each segment of the research requires different areas of expertise, said Dr. Lajos Pusztai, a breast cancer researcher at M. D. Anderson Cancer Center at the University of Texas. As a senior scientist, he added, “It’s true for me, too.”

The Duke case came right after two other claims that gave medical researchers pause. Like the Duke case, they used complex analyses to detect patterns of genes or cell proteins. But these were tests that were supposed to find ovarian cancer in patients’ blood. One, OvaSure, was developed by a Yale scientist, Dr. Gil G. Mor, licensed by the university and sold to patients before it was found to be useless.

The other, OvaCheck, was developed by a company, Correlogic, with contributions from scientists from the National Cancer Institute and the Food and Drug Administration. Major commercial labs licensed it and were about to start using it before two statisticians from M. D. Anderson discovered and publicized its faults.

The Duke saga began when a prestigious journal, Nature Medicine, published a paper on Nov. 6, 2006, by Dr. Anil Potti, a cancer researcher at Duke University Medical Center; Joseph R. Nevins, a senior scientist there; and their colleagues. They wrote about genomic tests they developed that looked at the molecular traits of a cancerous tumor and figured out which chemotherapy would work best.

Other groups of cancer researchers had been trying to do the same thing.

“Our group was despondent to get beaten out,” said Dr. John Minna, a lung cancer researcher at the University of Texas Southwestern Medical Center. But Dr. Minna rallied; at the very least, he thought, he would make use of this incredible discovery to select drugs for lung cancer patients.

First, though, he asked two statisticians at M. D. Anderson, Keith Baggerly and Kevin Coombes, to check the work. Several other doctors approached them with the same request.

Dr. Baggerly and Dr. Coombes found errors almost immediately. Some seemed careless — moving a row or a column over by one in a giant spreadsheet — while others seemed inexplicable. The Duke team shrugged them off as “clerical errors.”

And the Duke researchers continued to publish papers on their genomic signatures in prestigious journals. Meanwhile, they started three trials using the work to decide which drugs to give patients.

Dr. Baggerly and Dr. Coombes tried to sound an alarm. They got the attention of the National Cancer Institute, whose own investigators wanted to use the Duke system in a clinical trial but were dissuaded by the criticisms. Finally, they published their analysis in The Annals of Applied Statistics, a journal that medical scientists rarely read.

The situation finally grabbed the cancer world’s attention last July, not because of the efforts of Dr. Baggerly and Dr. Coombes, but because a trade publication, The Cancer Letter, reported that the lead researcher, Dr. Potti, had falsified parts of his résumé. He claimed, among other things, that he had been a Rhodes scholar.

“It took that to make people sit up and take notice,” said Dr. Steven Goodman, professor of oncology, pediatrics, epidemiology and biostatistics at Johns Hopkins University.

In the end, four gene signature papers were retracted. Duke shut down three trials using the results. Dr. Potti resigned from Duke. He declined to be interviewed for this article. His collaborator and mentor, Dr. Nevins, no longer directs one of Duke’s genomics centers.

The cancer world is reeling.

The Duke researchers had even set up a company — now disbanded — and planned to sell their test to determine cancer treatments. Duke cancer patients and their families, including Mrs. Jacobs’s husband, Walter Jacobs, say they feel angry and betrayed. And medical researchers see the story as a call to action. With such huge data sets and complicated analyses, researchers can no longer trust their hunches that a result does — or does not — make sense.

“Our intuition is pretty darn poor,” Dr. Baggerly said.

This article has been revised to reflect the following correction:

Correction: July 7, 2011

An earlier version of this post misstated Dr. Steven Goodman’s affiliation at Johns Hopkins University. He is a professor of oncology, pediatrics, epidemiology and biostatistics, not the director of oncology biostatistics.

In an article published online for the June 16 issue of The American Journal of Public Health, scientists calculated the number of deaths attributable to each of six social factors, including low income.

To estimate the number of deaths caused by each factor, the scientists reviewed 47 earlier studies on the subject, combining the data in a meta-analysis. The studies were generally based on large national surveys like the National Health and Nutrition Examination Survey, a continuing study by the Centers for Disease Control and Prevention.

Then, using the pooled data, the researchers calculated the “population-attributable fraction” of deaths — that is, the number of deaths caused by living with a given social disadvantage.

Finally, they multiplied that fraction by the total number of deaths in the year 2000 to come up with a number of deaths caused by each of the six social conditions. The researchers then separated the contribution of each social factor.

“The methods we’re using are limited,” Dr. Sandro Galea, the lead author, acknowledged. “Any time you try to say that death is attributable to a single cause, there’s a problem — all deaths are attributable to many causes. But what we did is just as valid as what was done to establish smoking as a cause of death.”

“This is a very interesting paper,” said Roger T. Anderson, a professor of public health sciences at Pennsylvania State College of Medicine who was not involved in the study. “It’s simple and elegant, a very straightforward approach to looking at these kinds of data.

“It brings to the surface what the impact of social disadvantage is in terms of numbers of deaths, and the authors have done a very nice job of laying out the argument.”

The researchers used various criteria to define an adverse social condition. Low education, for example, was defined as not having graduated from high school. Poverty was defined as a household income of less than $10,000. A population in which more than 25 percent of people reported their race or ethnicity as non-Hispanic black was considered racially segregated.

The study also calculated the effect of an area’s overall poverty level, income differential and low social support.

For 2000, the study attributed 176,000 deaths to racial segregation and 133,000 to individual poverty. The numbers are substantial. For example, looking at direct causes of death, 119,000 people in the United States die from accidents each year, and 156,000 from lung cancer.

Social factors are not the same as diseases or accidents, but Dr. Galea argues that they are equivalent to a behaviors like smoking, and that, as with smoking, there is evidence of the mechanism involved. He said that the causal chain between, for example, poverty and death from heart disease has many well-established links.

Dr. Galea also said that poverty results in poor access to health screening, poor access to quality care for those who actually have heart disease, greater vulnerability to stresses associated with heart disease and a greater likelihood of engaging in unhealthy behavior.

“In some ways,” Dr. Galea added, “the question is not ‘Why should we think of poverty as a cause of death?’ but rather ‘Why should we not think of poverty as a cause of death?’ ”

If they had not smoked, 400,000 people each year would not have died, Dr. Galea said. Similarly, he said, if they had graduated from high school, the 245,000 people whose cause of death he attributes to low education would still be alive.

“This might be a useful lens to help focus our minds,” said Dr. Galea, who is the chairman of the department of epidemiology at the Mailman School of Public Health at Columbia University. “If you say that 193,000 deaths are due to heart attack, then heart attack matters. If you say 300,000 deaths are due to obesity, then obesity matters.

“Well, if 291,000 deaths are due to poverty and income inequality, then those things matter too.”

]]> http://www.bioethicsinternational.org/blog/2011/07/05/researchers-link-deaths-to-social-ills/feed/ 0 http://www.bioethicsinternational.org/blog/2011/07/02/medtronics-infuse-bone-growth-therapy/ http://www.bioethicsinternational.org/blog/2011/07/02/medtronics-infuse-bone-growth-therapy/#comments Sat, 02 Jul 2011 10:00:25 +0000 Lauren Rushing, BEI Intern http://www.bioethicsinternational.org/blog/?p=2449 [MassDevice] A new study alleges that Medtronic’s Infuse bone growth product causes excess bone growth in the spinal canal and researchers on the company payroll covered it up.

MASSDEVICE ON CALL — Medtronic Inc. (NYSE:MDT) faces new heat over the Infuse bone growth product, this time for allegations that the therapy caused excess bone growth in the spinal canal of 70 percent of patients in an independent clinical trial.

In what has become a familiar cry against the Infuse product, doctors on the company’s payroll were accused of concealing vital information from published studies.

A 2004 paper written about a clinical trial conducted by MDT’s paid consultants maintained that no harm was done to patients and that any excess bone growth, known as ectopic bone, didn’t cause any ill effects.

Just a few months ago, a clinical trial found that nearly three quarters of patients had unwanted bone growth in their spinal canals, and the trial was cut off after only 34 of hundreds of enrolled patients had received the implant, the Milwaukee Journal Sentinel reported.

The allegations continue to stack the deck against the Infuse implant, which has been widely used to fuse spinal vertebrae during surgeries since 2002.

A study published last month accused the Fridley, Minn.-based company of concealing that the bio-engineered bone growth protein can increase the risk of infertility in men. Last week two U.S. Senators demanded that the medical device giant turn over documents relating to internal correspondence with paid consultants and researchers who worked on product trials, expanding the investigation into whether physicians on the company’s payroll concealed the infertility risk.

A critical review of Infuse’s complications will be published in the Spine Journal this week.

Bioethicists and researchers spoke Tuesday before a presidential panel in Washington. The meeting was triggered by the government’s apology last fall for federal doctors infecting prisoners and mental patients in Guatemala with syphilis 65 years ago.

President Barack Obama ordered his Commission for the Study of Bioethical Issues to explore whether such a study could ever happen again.

Speakers noted that over the last several decades, as many as 1,000 rules, regulations and guidelines have been enacted worldwide to ensure the ethical conduct of medical research. In the United States, there are rules to protect people in every study done by federal scientists, funded by federal agencies or those testing a product requiring federal approval to be sold.

But that oversight is inconsistent – ethical rules can vary among federal agencies. What’s more, if federal funding or review is not involved, an unethical study could be done and no one in authority would ever know about it.

“We have a leaky system,” said Eric Meslin, director of the Indiana University Center for Bioethics.

Dr. Robert Califf, Duke University’s vice chancellor for clinical research, agreed there are weaknesses.

“It’s night and day and what you could do in the ‘good old days’ with no one knowing about it. But there’s no 100 percent guarantee. There still will be bad things that will happen,” he said.

The commission, ordered to report to the president by September, was given two tasks:

-Examine federally funded international studies to make sure research is being done ethically. The commission named a 14-member international panel of experts to study the question.

-Take a more intensive look at the Guatemala study. More than a dozen commission investigators have already started poring through hundreds of boxes of old government documents.

What they will turn up is unknown, but there are doubtless more unethical studies from the past that have never been publicly reported, said Susan Lederer, a medical historian at the University of Wisconsin.

On Sunday, The Associated Press reported on dozens of studies from the past – most of them between 40 and 80 years ago – involving researchers deliberately infecting people to study the effects of diseases or to see if an experimental treatment might work.

The AP investigation itself was triggered by the Guatemala study.

At Tuesday’s commission meeting, Lederer was the most pessimistic of five guest speakers about whether that kind of research could happen again.

“I don’t think you should look to historians for optimism,” she said.

*Pictured Above: The infamous Tuskegee syphilis experiment conducted between 1932 and 1972.

Still to be voted on late Sunday night was a companion bill making changes to the Senate bill, a measure necessary to attract support in the House. After House approval, those changes still need to go before the Senate.

President Barack Obama, who staked his presidency on the health-care overhaul, helped push it toward passage with a last-minute promise to issue an executive order making clear that no money dispensed under the $940 billion bill would pay for abortions. That persuaded Rep. Bart Stupak, a holdout Michigan Democrat, to vote yes and bring at least seven colleagues with him.

It was a tumultuous sprint to the finish for legislation that has brought Washington many dramas over the last year, ranging from a Christmas Eve Senate vote to the surprise January election of Massachusetts Republican Sen. Scott Brown that upended Democrats’ plans.

“It makes me so happy that, after 100 years, we can finally catch up with the rest of the world,” Rules Committee Chairwoman Louise Slaughter, a New York Democrat, said as House leaders became confident they had the votes for passage.

Rep. John Shadegg (R., Ariz.) said the legislation represents an overreach by the government. “This bill will destroy freedom, and do incredible damage to the very fabric of our society,” he said.

Republicans hope to use the health overhaul to drive Democrats into the minority, citing polls that show a plurality of Americans oppose it, while Democrats believe the immediate benefits brought by the bill will work to their credit.

The legislation will extend health coverage to 32 million Americans now without insurance, according to the Congressional Budget Office. It will mandate that almost every American carry health insurance—a provision that opponents are set to challenge in the courts. To help people get covered, the legislation expands Medicaid, the federal-state health program for the poor, and gives subsidies to families making as much as $88,000 a year.

Democrats are highlighting popular provisions, such as one that requires insurance companies to accept all comers, even people who are already sick. Republican critics are stressing new taxes in the bill and trims to Medicare spending needed to fund the subsidies.

The broad Senate bill was set to become law quickly following House passage. Some uncertainty remained over the package of changes, which are expected to go to the Senate later this week. Senate Democratic leaders said they had the votes to approve it, but Republican efforts to torpedo it or change it could complicate passage. The changes would boost the value of the subsidies and nullify special deals for some senators that caused a storm of protest.

The CBO estimates the package will hold the federal budget deficit $143 billion lower over 10 years than it would otherwise be. Republicans called the estimate unrealistic. The CBO also estimated that 95% of legal U.S. residents would have insurance by 2019, up from 83% today.

The march toward action Sunday was greeted by protests from hundreds of Tea Party activists, who filled the Capitol grounds, and Republican complaints about the last-minute bargaining among Democrats. “Where has the transparency been? Why all the back-room deals?” asked Rep. Jack Kingston (R., Ga.).  

The focus Sunday was largely on resolving the abortion dispute. Several Democrats, led by Rep. Stupak, had been withholding support, saying the legislation didn’t go far enough to keep federal funds from being used to pay for abortions. They praised Mr. Obama’s executive order, while Roman Catholic bishops and other antiabortion groups said it wasn’t good enough.

Insurers will see the heaviest regulations, with new rules that dictate how much they can reap in profit and whom they must cover.

Hospitals, doctors, drug makers and the seniors group AARP backed the overhaul, saying it will reduce the growth of health costs and make sure no one goes without care..

“This is not about health care,” said Rep. James Clyburn of South Carolina, the House Democratic whip. “It’s about trying to extend a basic fundamental right to people who are less powerful.”

Francee Levin, a 57-year-old artist in Columbia, S.C., said she couldn’t get health insurance after she was hit by a drunk driver. “I think I’ll be able to get some kind of health insurance, which would be a godsend,” she said.

But Catherine Calhoun of Saint Francisville, La., said she worried her husband’s employer might drop coverage and force the family to go into newly created health-insurance exchanges to get coverage. That might force her to find new doctors for her 7-year-old son, Billy, who has a rare bone disease, she said.

“I might end up having to negotiate with someone who doesn’t have any idea what he needs just to get out of bed in the morning,” said Ms. Calhoun.

In the run-up to the vote, Mr. Obama urged House Democrats to focus on those helped by the bill and not worry about the difficult politics. “Good policy is good politics,” he said.

Republicans said they expect big gains in the fall. “I’d rather be a Republican running against his bill and saying, ‘Let’s start over,’” said Sen. John Cornyn (R., Texas), chairman of the National Republican Senatorial Committee. “This will be the defining issue in November 2010, and if it passes, in 2012 when the president runs for re-election.”

Under the legislation, consumers will see changes within months. Insurers won’t be able to place lifetime limits on coverage. Children will be able to stay on their parents’ insurance policies until their 26th birthday. The changes could be bumpy, because insurers warn they won’t be able to make them so quickly. 

The bulk of the legislation wouldn’t take effect until 2014. Once the tax credits and Medicaid expansion are in place, most Americans will be required to carry health insurance or pay a fee, topping out at either $695 a year or 2.5% of income.

Employers would have to provide affordable insurance or pay a penalty of up to $3,000 per worker. Those figures assume the Senate ultimately adopts the package of changes the House was voting on.

Tax increases needed to finance the program would hit a range of industries, from insurers to tanning services. Over the next decade, $108 billion in new fees will fall on insurers, drug makers and medical-device companies. Families earning more than $250,000 a year will pay a higher Medicare payroll tax, and see that tax expanded to investment income such as dividends. High-value insurance plans would be hit with a 40% tax starting in 2018.

As part of the second bill headed toward a vote, Mr. Obama was poised to accomplish another big goal: overhauling the federal student-loan program. It would end subsidies to banks and shift lending responsibilities to the federal government. That is part of the package of changes still requiring Senate approval.

Write to Janet Adamy at janet.adamy@wsj.com and Greg Hitt at greg.hitt@wsj.com

The developer, Osiris Therapeutics, said Tuesday that its drug, Prochymal, was no more effective, over all, than a placebo in treating a life-threatening complication of bone marrow transplantation, though certain patients seemed to be helped. Shares of Osiris, which is based in Columbia, Md., fell 34 percent, to $8.03.

Prochymal is a preparation of mesenchymal stem cells, which are obtained from the bone marrow of healthy young adults. Because the cells are derived from adults, they sidestep the ethical issues stemming from the destruction of human embryos needed to make embryonic stem cells. Unlike most other types of adult stem cells, mesenchymal cells grow well in culture, so thousands of doses can be produced from a single donation.

Stem cells, particularly in the form of bone marrow transplants, are already used in medicine. Osiris is hoping that Prochymal will become the first stem cell product approved by the Food and Drug Administration and sold as a mass-produced pharmaceutical product.

But the failure in the two trials could make it hard to reach that goal. Both trials tested Prochymal as a treatment for graft-versus-host disease, which occurs when immune cells in donated marrow attack the recipient’s organs as foreign tissue.

In one trial, in which Prochymal was used along with steroids, 45 percent of patients responded to Prochymal and steroids compared with 46 percent who had a response to steroid and a placebo.

In a second trial, in which Prochymal was tested in patients who were not benefiting from steroids, 35 percent of those getting the drug had a resolution of graft-versus-host disease for at least 28 days, compared with 30 percent getting the placebo. The difference was not statistically significant.

Osiris said, however, that in the second trial, the drug did provide a statistically meaningful benefit in patients having graft-versus-host disease that specifically affected their livers or their gastrointestinal tracts.

C. Randal Mills, the company’s chief executive, said he hoped the drug could be approved for those patients, given the seriousness of the disease. “Prochymal is having a clear effect in the liver, and that is the most underserved patient population,” he said in an interview.

But the F.D.A. is usually reluctant to approve a drug based on its working in only a subset of patients.

In March, Osiris stopped enrollment in a trial testing Prochymal as a treatment for Crohn’s disease, saying it was unlikely the drug would be better than a placebo, because of a high positive response to the placebo. Genzyme has the right to sell Prochymal outside the United States and Canada.

Dr. Darwin J. Prockop, an expert on mesenchymal stem cells who was not involved in the trials, said there were still a lot of unknowns about how the cells work. “Understanding it well enough to translate to the clinic — that’s the hurdle we’re at,” said Dr. Prockop, who is director of the Institute for Regenerative Medicine at Texas A&M Health Science Center.

A national survey for the Indiana University Center for Health Policy and Professionalism Research and the Indiana University Center for Bioethics says about six out of 10 Americans — 78 percent of Republicans, 30 percent of Democrats, 58 percent of Independents — say they believe under healthcare reform taxpayers will have to pay for abortions, something Dr. Aaron Carroll, director of CHPPR, says is untrue.

Sixty-seven percent of Americans — 91 percent of Republicans, 37 percent of Democrats, 72 percent of Independents — say they believe wait times for healthcare services such as surgery will increase after healthcare reform.

Forty-six percent — 66 percent of Republicans, 29 percent of Democrats, 43 percent of Independents — say they believe reforms will result in healthcare coverage for all illegal immigrants. Three out of 10 Americans — 53 percent of Republicans, 14 percent of Democrats, 31 percent of Independents — say they believe after reforms the government will require the elderly to make decisions about how and when they will die.

If the White House hopes to convince the majority of Americans that they are misinformed about healthcare reform, there is much work to be done, Carroll says in a statement.

The poll of 600 U.S. adults, conducted by Market Strategies International Aug. 14-18, has a margin of error of plus/minus 4 percentage points.

Source: United Press International