Fight terrorism

GAITHERSBURG, Md. — A federal medical advisory panel recommended Wednesday that Avandia, a controversial diabetes drug, should either be withdrawn from the market or have sales severely restricted because it increases the risks of heart attacks.

Documents released on Tuesday by the Senate Finance Committee chronicle discussions within GlaxoSmithKline about its controversial diabetes drug Avandia.

The panel’s votes, taken after two days of intensive scientific discussions, were a blow to GlaxoSmithKline, which makes Avandia. The company argued that Avandia is a safe and needed option in treating diabetes.

But panel members voiced great skepticism about the company’s trustworthiness after questions were raised about its clinical trials. And internal company documents showed that the company for years kept crucial safety information about Avandia from the public.

The panel took six votes on a variety of issues, but its most important came near the end of the meeting when asked what the Food and Drug Administration should do. Of the panel’s 33 members, 12 voted that Avandia should be withdrawn; 10 voted that its sales should be restricted and the warnings on its label enhanced; 7 voted only to support enhanced warnings on the drug’s label; and 3 voted that the drug should continue to be sold with its present warnings unchanged. One member abstained, and no one voted for a final option, to weaken the label’s present heart warnings.

Dr. Janet Woodcock, director of the drug center at the F.D.A., said that the agency took the panel’s advice seriously and that it would consider its regulatory options.

The F.D.A. often takes the advice of its advisory panels, but in this case it was hard to predict what the agency would do, given the split nature of the vote. The agency allowed competing visions to spill out in the advisory hearing — something unheard of just a few years ago, when the F.D.A. nearly always spoke with a single voice.

“We will come to a decision as soon as possible, and we will announce that publicly,” Dr. Woodcock said.

Approved in 1999, Avandia helps control blood sugar levels in diabetics by making patients more sensitive to their own insulin. It is one of a class of three drugs, the first of which, Rezulin, was withdrawn because it caused liver damage. The other drug in the class, Actos, made by Takeda, has appeared safe.

Avandia, which was once the biggest-selling diabetes medicine in the world, saw its sales abruptly decline in 2007 after a study by Dr. Steven Nissen, a Cleveland Clinic cardiologist, found that it increased the risk of heart attacks. An advisory committee in 2007 decided that Avandia did increase heart risks but voted to keep it on the market.

Many of the same experts who decided to keep the drug on the market in 2007 voted Wednesday that it should be withdrawn or restricted. Those restrictions could mean that patients would have to apply for special permission to use the drug.

Reactions were as mixed as the vote.

In a statement shortly after the committee adjourned, GlaxoSmithKline noted that a majority of committee members had voted to keep Avandia on the market.

Dr. Nissen said the committee’s vote was the best he could hope for. “Effectively, this drug is gone,” he said.

Dr. Sanjay Kaul, who voted to require stronger warnings, said that the F.D.A. must ensure that Avandia was used far less regularly. “Make sure this is available as second-line and not as first-line,” Dr. Kaul urged.

The F.D.A. generally undertakes programs to restrict a drug’s sales only when a drug offers a unique benefit, something no study has shown about Avandia. Among the examples of drugs the F.D.A. has restricted are Accutane, an acne drug that can cause birth defects, and Lotronex, a drug for irritable bowel disease that in rare instances is fatal. A majority of the committee found that Avandia increased the risk of heart attacks but a majority also said that studies had failed to prove it increased the risk of death. A majority also decided that if Avandia were to continue to be sold, the company should complete a clinical trial to prove it was safe. But several members said that the vote probably made a trial impossible because patients would not want to risk taking Avandia.

GlaxoSmithKline said it was in the midst of a clinical trial that would test definitively if Avandia caused heart attacks. Several panel members said the trial came too late.

“The best time to do the trial would have been when the first signal about lipids came up way back in the 1990s,” said Dr. Peter J. Savage, a member from the National Institute of Diabetes, Digestive and Kidney Diseases.

In the 1990s, GlaxoSmithKline decided against just such a study because it feared that the results might hurt sales, according to internal company documents.

Throughout the meeting, GlaxoSmithKline was criticized over repeated findings by federal officials that the company had failed to conduct its Avandia studies appropriately.

At one point, Dr. Murray Stewart, a vice president at GlaxoSmithKline, was given five minutes to explain why a crucial trial called Record was done properly.

But he was immediately followed by Dr. Thomas A. Marciniak, a team leader at the F.D.A., who found numerous mistakes in the study that served to hide Avandia’s risks.

Time and again, GlaxoSmithKline overruled doctors who had concluded that patients had been harmed by Avandia, Dr. Marciniak said.

Dr. Stewart tried to respond, but the committee’s chairman silenced him.

Dr. William Knowler, a panel member who is chief of diabetes epidemiology at the National institute of Diabetes and Digestives and Kidney Diseases, described a different study done by GlaxoSmithKline as “totally incorrect and deceptive.”

Dr. David Capuzzi, a panel member who treats diabetics, said that clinicians need as many choices of drugs as possible, and he voted to keep Avandia on the market with no new restrictions.

Chuck Keyserling, a diabetes patient, echoed those concerns during a brief public part of the meeting. He said that he had been taking Avandia for 10 years.

“Please think about those of us who have flourished on Avandia,” Mr. Keyserling told the panel. “For those people, a negative position on Avandia may be a death sentence.”

Dr. John Teerlink, a panel member who voted Wednesday to restrict the drug, said he had served on the advisory panel in 2007 that voted to continue to allow Avandia to be marketed. But he said he made the earlier vote with the understanding that GlaxoSmithKline would use the added time to prove that its drug was safe and that he had not been convinced.

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Jimmy Weekley, who lives in Pigeonroost Hollow, W.Va., has been fighting the Spruce 1 coal project for years. More Photos »

BLAIR, W.Va. — Federal officials are considering whether to veto mountaintop mining above a little Appalachian valley called Pigeonroost Hollow, a step that could be a turning point for one of the country’s most contentious environmental disputes.

Above is an existing mining operation, adjacent to the Spruce 1 site, which is to the upper left of the cleared areas. More Photos »

The Army Corps of Engineers approved a permit in 2007 to blast 400 feet off the hilltops here to expose the rich coal seams, disposing of the debris in the upper reaches of six valleys, including Pigeonroost Hollow.

But the Environmental Protection Agency under the Obama administration, in a break with President George W. Bush’s more coal-friendly approach, has threatened to halt or sharply scale back the project known as Spruce 1. The agency asserts that the project would irrevocably damage streams and wildlife and violate the Clean Water Act.

Because it is one of the largest mountaintop mining projects ever and because it has been hotly disputed for a dozen years, Spruce 1 is seen as a bellwether by conservation groups and the coal industry.

The fate of the project could also have national reverberations, affecting Democratic Party prospects in coal states. While extensive research and public hearings on the plan have been completed, federal officials said that their final decision would not be announced until late this year — perhaps, conveniently, after the midterm elections.

Environmental groups say that approval of the project in anything like its current form would be a betrayal.

“Spruce 1 is a test of whether the E.P.A. is going to follow through with its promises,” said Bill Price, director of environmental justice with the Sierra Club in West Virginia.

“If the administration sticks to its guns,” Mr. Price predicted, “mountaintop removal is going to be severely curtailed.”

Coal companies say politics, not science, is threatening a practice vital to local economies and energy independence. “After years of study, with the company doing everything any agency asked, and three years after a permit was issued, the E.P.A. now wants to stop Spruce 1,” said Bill Raney, president of the West Virginia Coal Association. “It’s political; the only thing that has changed is the administration.”

While the government does not collect statistics on mountaintop mining, data suggest that it may account for about 10 percent of American coal output, yielding 5 percent of the nation’s electricity. The method plays a bigger economic role in the two states where it is concentrated, Kentucky and West Virginia.

The proposal to strip a large area above the home of 70-year-old Jimmy Weekley, Pigeonroost Hollow’s last remaining inhabitant, was first made in 1997 by Arch Coal, Inc., of St. Louis. The legal ups and downs of Spruce 1 have come to symbolize the broader battle over a method that produces inexpensive coal while drastically altering the landscape.

Spruce 1 started as the largest single proposal ever for hilltop mining, in which mountains are carved off to expose coal seams and much of the debris, often leaking toxic substances, is placed in adjacent valleys.

After years of negotiations and a scaling back of the mining area to 2,278 acres, from its original 3,113 acres, the Spruce 1 permit was approved by the Army Corps of Engineers in 2007 and limited construction began. But this spring, the E.P.A. proposed halting the project.

The announcement caused an uproar in West Virginia. The E.P.A. held an emotional public hearing in May and stopped accepting written comments in June. Arch Coal has objected publicly, but did not respond to requests to comment for this article.

The Obama administration’s E.P.A. has already riled the coal companies by tightening procedures for issuing new mining permits and imposing stronger stream protections. But environmental groups were worried in June, when the agency approved a curtailed mountaintop plan in another site in Logan County, W.Va. Now, as negotiations between the E.P.A. and Arch Coal continue, the Spruce 1 battle is being closely watched as a sign of mountaintop mining’s future.

Feelings run high in the counties right around the project area.

“Spruce 1 is extremely important to all of southern West Virginia because if this permit is pulled back, every mine site is going to be vulnerable to having its permits pulled,” said James Milan, manager of Walker Machinery in Logan, which sells gargantuan Caterpillar equipment.

The loss of jobs, Mr. Milan said, would have devastating effects on struggling communities.

Maria Gunnoe, an organizer for the Ohio Valley Environmental Coalition and a director of SouthWings, which organizes flights to document environmental damages, said that if Spruce 1 went forward, “it’s going to mean the permanent erasure of part of our land and our legacy.”

“We can’t keep blowing up mountains to keep the lights on,” said Ms. Gunnoe, a resident of nearby Boone County who has received death threats and travels with a 9 millimeter pistol.

Mr. Weekley, whose house is in sight of the project boundary, remembers the day in 1997 when he decided to fight it. Nearby mining under previous permits had filled his wooded valley with dust and noise.

“You couldn’t see out of this hollow,” he recalled. “I said, Something’s got to be done or we’re not going to have a community left.”

He and his late wife became plaintiffs in a 2008 suit claiming that the project violated environmental laws. A ruling in their favor was overturned, setting off litigation that continues.

Mr. Weekley said that he had rejected offers of close to $2 million for his eight acres and that he had seen the population of the nearby town of Blair dwindle to 60 from 600, with most residents bought out by Arch Coal.

A rail-thin man who enjoys sitting on his porch with a dog on his lap, Mr. Weekley uttered an expletive when told that coal industry representatives, including Mr. Raney in an interview, referred to the upper tributaries filled in by mining as “ditches” that can be rebuilt. In fact, some of the streams to be filled by Spruce 1 are intermittent, while others, including Pigeonroost Creek, flow year-round.

“I caught fish in that stream as a child, using a safety pin for a hook,” Mr. Weekley said. “If they get that permit, there won’t be a stream here.”

In documents issued in March, the E.P.A. said the project as approved would still smother seven miles of streambed.

Filling in headwaters damages the web of life downstream, from aquatic insects to salamanders to fish, and temporary channels and rebuilt streams are no substitute, the agency said. The pulverized rock can release toxic levels of selenium and other pollutants, it noted.

The effects of Spruce 1 would be added to those of 34 other past and present projects that together account for more than one-third of the area of the Spruce Fork watershed, the agency said.

The debate over Spruce 1 and other mountaintop mine permits has been a source of division and anguish among local residents.

Michael Fox, 39, of Gilbert, is a mine worker who like many other miners here thinks the objections are overblown. “I have three kids I want to send to college,” Mr. Fox said.

One former mountaintop miner who says he now regrets his involvement is Charles Bella, 60. He is one of the remaining residents on Blair’s main street, along the Spruce Fork, which is fed in turn by Pigeonroost Creek.

“I know it put bread on my table, but I hate destroying the mountains like that,” Mr. Bella said.

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WASHINGTON — President Obama and Senate Democrats have decided to press ahead in the next two weeks with a scaled-back energy bill that limits carbon pollution by power plants but not by other industries in an effort to salvage the legislation before midterm elections.

The latest on President Obama, his administration and other news from Washington and around the nation. Join the discussion.

After months of gridlock, the White House and Democratic leaders have concluded that the sweeping measure they once envisioned cannot pass, so they will try to get what they can rather than pass nothing at all. The developing plan is intended to appeal to enough Republicans to overcome a filibuster but could disappoint liberals who argue that more needs to be done.

“If not now, when?” said Senator Harry M. Reid of Nevada, the Democratic majority leader, who plans to bring the compromise bill to the Senate floor the week of July 26. “We have to move to do something about our dependence on foreign oil. That’s what this legislation is all about.”

Mr. Reid also presented it as a way to further stimulate the economy, saying, “This as I’ve indicated is a huge jobs bill.”

The strategy of pushing forward with a more limited bill acknowledges the complicated politics in the Senate and the short time on the clock with elections approaching.

While the House last year passed a measure capping the greenhouse gases blamed for climate change across the economy, the White House and its Senate allies will push only to limit those from electric utilities, which are responsible for about a third of the emissions produced by the United States.

Such a measure would allow Mr. Obama to make a down payment on his larger goal.

“He’s always believed there should be an economywide solution but recognizes that may not be where we are,” Carol M. Browner, the president’s energy and climate adviser, said in an interview. “Getting started is hugely important, and he’s willing to work with senators in that direction.”

Passage would also give the president another legislative victory following the overhaul of the health care system passed in March and new regulations for Wall Street expected to pass this week. And House Democrats said it would be a relief for them to have at least something pass since they have been left trying to explain politically dicey votes for the broader cap.

It remains far from certain, however, that Mr. Obama and Mr. Reid can win passage even for the limited legislation. Most Republicans remain firm in their opposition to any cap on emissions, and six Democrats recently joined an effort by Senator Lisa Murkowski, Republican of Alaska, to pass a resolution criticizing new Environmental Protection Agency rules relating to greenhouse gases.

“Senator Murkowski won’t support a utility cap-and-trade bill because it raises energy prices on Americans at a time when they are already struggling financially,” said Robert Dillon, a spokesman for the senator. “It’s a light-switch tax.”

Moreover, the utility industry has expressed reservations or sought concessions, like pulling back on new pollution rules in other areas, something White House officials rejected last week at a meeting with industry representatives on Capitol Hill.

The National Rural Electric Cooperative Association “has consistently called for an economywide approach,” said Tracy Warren, a group spokeswoman.

Some environmental advocates said they were resigned to the new approach. “Is it adequate to address the problem? No,” said Daniel J. Weiss, the director of climate strategy at the Center for American Progress, a liberal research organization. “Is it a good plan to start, given where we are with the calendar and politically? Yes.”

By some calculations, the White House and Senate Democrats have only until the August recess to pass a meaningful energy bill this year. Few expect serious legislation to pass in the fall with members focusing on re-election campaigns.

Mr. Obama has been pushing for the legislation by meeting with senators and holding events to highlight clean-energy projects. He plans to fly to Holland, Mich., on Thursday for the groundbreaking of a plant manufacturing batteries for electric cars, financed in part by his stimulus program.

Several senators, including John Kerry, Democrat of Massachusetts, and Joseph I. Lieberman, independent of Connecticut, are trying to create specific plans to draw enough votes across the aisle.

Mr. Reid outlined four main elements: responding to the Gulf of Mexico oil spill, promoting greater energy efficiency, developing more clean-energy production and curbing power plant emissions.

He said he was prepared to incorporate a plan championed by T. Boone Pickens, the oil and gas executive, to sharply expand the use of natural gas as a transportation fuel in large vehicle fleets. The proposal, supported by Senators Orrin G. Hatch, Republican of Utah, and Robert Menendez, Democrat of New Jersey, would provide tax breaks for natural-gas-powered vehicles and fueling stations.

“This legislation, it’s not all green stuff — you know, Sierra Club stuff,” Mr. Reid said. “We’re importing 70 percent of the oil that we use. We have a need to change the paradigm in America. And that is, we need to have a move to renewable energy.”

The White House and Senate Democratic leaders hope to appeal to several Republicans, like Senators Olympia J. Snowe and Susan M. Collins of Maine, Scott Brown of Massachusetts, Richard G. Lugar of Indiana and George LeMieux of Florida.

Democrats said that if the utility cap was drawn narrowly enough, they hoped to win over Senator Lindsey Graham, Republican of South Carolina, who helped draft the initial plan by Mr. Kerry and Mr. Lieberman before withdrawing his support.

But Democratic aides conceded that they could lose even more Democrats from coal-producing states. If the utility cap fails to win the 60 votes needed to overcome a filibuster, the White House and Senate Democrats will be faced with a tough choice: go ahead with the rest of the bill or pull the whole thing.

Some Democratic senators worry that a so-called energy-only bill investing in alternative-energy development without any limits on carbon emissions would effectively give away the popular policy items necessary for any eventual deal.

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MOSCOW — Russia’s energy minister announced a broad program of cooperation with Iran in the oil, natural gas and petrochemical industries on Wednesday that appeared to invite Russian companies to contravene sanctions the Obama administration adopted just two weeks ago.

The sanctions were meant to be an additional means of punishing Iran for refusing to unwind its secretive nuclear program after the United States was able to persuade Russia and China to agree to only limited new trade restrictions in a fourth United Nations Security Council resolution against Iran, passed in June. Australia, Canada and Europe also decided to put additional measures against Iran in place.

While clearly intended to discourage the type of investment the Russian minister discussed, the United States sanctions law provides a presidential waiver for companies in countries otherwise seen as cooperating in discouraging Iran from obtaining a nuclear weapon.

Iran, though a major exporter of crude oil, imports tens of thousands of gallons of gasoline daily to make up for its faltering refining capacity, limited by years of international isolation.

The American sanctions impose penalties on foreign entities that sell refined petroleum to Iran or assist Iran with its domestic refining capacity, a focus intended to exact a harsh financial toll on the Islamic Revolutionary Guards Corps, the hard-line group that oversees the country’s nuclear and missile programs and controls much of its oil industry.

Russia’s president, Dmitri A. Medvedev, voiced opposition to adding any sanctions beyond those imposed by the United Nations, and the Foreign Ministry warned the United States against trying to punish Russian companies under the new unilateral sanctions.

On Wednesday, Russia’s minister of fuel and energy took the most overt stance against the American sanctions so far, announcing the plans for closer cooperation between Russian and Iranian petroleum interests.

The minister, Sergei I. Shmatko, met in Moscow with his Iranian counterpart, Massoud Mir-Kazemi, and issued a joint statement praising “active cooperation between Russian and Iranian companies in the oil, gas and petrochemical sectors, which are developing and widening in their joint work.”

But it was unclear how immediately action would be taken. The Russian statement suggested that a working group be formed to identify areas of deeper cooperation in the oil and petrochemical industries, proposing a study for a Russian-Iranian joint venture oil company and a binational bank to finance such projects. The statement suggested Iran market its crude oil on Russian commodity exchanges.

The oil dealings between the countries would force the United States to make difficult choices only if Russian companies followed through on the broad plans with specific agreements, Cliff Kupchan, a research director at the Eurasia Group, said in a telephone interview.

And this seemed unlikely, at least at the moment, he said, given the recent warming in bilateral relations with the United States, Russian backing for the United Nations sanctions against Iran and the successful spy swap this month.

Sergei A. Karaganov, a dean of the faculty of international relations at the Higher School of Economics in Moscow, said Russia would resist sanctions that could harm the economic well-being of a wide portion of Iran’s population and add to political turmoil.

The gasoline embargo imposed by the United States could do both, Mr. Karaganov said.

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A Palestinian helped build a synagogue this month in a Jewish settlement in the West Bank.

JERUSALEM — In the upbeat atmosphere after their recent meeting in Washington, the prime minister of Israel, Benjamin Netanyahu, and President Obama expressed hopes of an imminent resumption of direct Israeli-Palestinian peace talks and of achieving a peace deal — within a year, according to Mr. Netanyahu, or in Mr. Obama’s case, before the end of his term.

There has been vague talk in Washington about a narrowing of gaps in the weeks since the indirect, American-brokered negotiations started in May.

But back on home turf, with no evidence of political progress, the mood seems less sanguine, even contradictory, as Palestinian officials and analysts suggest that the so-called proximity talks have merely accentuated the deep and abiding differences between the sides.

“It is clear that Mr. Netanyahu is playing for time,” said Khalil Shikaki, a prominent Palestinian political analyst in the West Bank. “He knows that anything he has to say has already been long, long passed by.”

Little has been revealed about the content of the indirect discussions, mediated by Mr. Obama’s Middle East envoy, George J. Mitchell. But the impression gained from a series of public statements and private conversations with officials and analysts over the past few weeks is that they have largely been taking place on parallel tracks.

The Palestinians said they wanted to focus on borders and security in the four months that were budgeted for the talks. Israel said it had focused on the water issue in one of the early rounds.

This month, as the proximity talks approached their halfway mark, Saeb Erekat, the chief Palestinian negotiator, said that the Palestinians had submitted their positions to Mr. Mitchell in full. “We have yet to hear any response on any issue, including borders,” he said.

Israeli officials said they were not willing to define a border until they received clear answers from the Palestinians about the nature of the state they intend to establish on the other side.

“Will it be demilitarized?” asked one Israeli official who was not authorized to discuss details of the proximity talks publicly. “Will it accept Israel as a Jewish state? These are the questions we will be raising.”

The Palestinians have skirted the issue of demilitarization and consistently rejected demands to recognize the Jewish character of Israel.

A senior Israeli minister, Dan Meridor, recently told reporters that it would be “very risky” for Israel to fix borders and leave other major issues unresolved. Specifically, he said, Israel cannot agree on borders before ensuring that the solution to the Palestinian refugee issue lies not in Israel, but on the other side of the lines.

Adding to the discord, Mr. Erekat recently raised a new bar for the start of direct talks. Alongside the longstanding demand for a complete freeze in settlement building, including in East Jerusalem, which the Israelis have refused, Mr. Erekat said talks should start from the point at which the last direct negotiations, between the Palestinians and the previous, centrist Israeli government, left off in December 2008.

He also said that Mr. Netanyahu should state his readiness to recognize a Palestinian state based on the 1967 lines.

Both these positions are deemed unacceptable by Mr. Netanyahu’s conservative-dominated governing coalition. Yet the Palestinians seem open to entering direct talks, and have been careful not to set firm preconditions.

The basis for direct talks is likely to be Secretary of State Hillary Rodham Clinton’s carefully shaped formula of last November. She said she believed that the two sides, through negotiations, could reconcile “the Palestinian goal of an independent and viable state, based on the 1967 lines, with agreed swaps, and the Israeli goal of a Jewish state with secure and recognized borders that reflect subsequent developments and meet Israeli security requirements.”

Mrs. Clinton’s statement came soon after Mr. Netanyahu announced a partial, 10-month moratorium in new Israeli residential building in the West Bank. Mr. Netanyahu has been generally cagey about whether he will ask his government to extend the moratorium beyond its Sept. 26 deadline. Officials said that Mr. Netanyahu discussed other confidence-building measures with Mr. Obama, to be carried out either in the prelude to, or during, direct talks.

Mr. Netanyahu’s predecessor, Ehud Olmert, made a far-reaching proposal in late 2008 to the Palestinian president, Mahmoud Abbas. It included an Israeli withdrawal from 93.5 percent of the West Bank, with land swaps and a safe route for Palestinian travel between Gaza and the West Bank making up the other 6.5 percent of the land area that Israel won in 1967.

Those talks ended with Israel’s military campaign against Gaza, which is run by the militant group Hamas. Mr. Olmert says he never heard back from Mr. Abbas.

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