"There has been a shift back to more conservatism on two fronts," says Fred Hassan, chairman and chief executive at Schering-Plough Corp. "Companies have become more conservative about the types of products they are promoting in their pipelines. ...And the FDA is taking a closer look, and that's slowing the rate of approval." He added: "It's also affecting the industry bottom line."

Following the uproar over pediatric antidepressants, major medical journals set a policy requiring companies to register clinical trials in a publicly available database before they are launched if they want the results to be considered for publication. The idea behind the policy: Negative results from clinical trials couldn't be kept from public view as if the trials had never occurred.

Regulatory initiatives will force the industry to make public much more information about drug testing than it has in the past. One initiative in California requires disclosure of financial arrangements between companies and physicians who participate in clinical trials.

"It's going to be a much more open industry in ways that can't be fully predicted yet," says Paul Blake, executive vice president, medical and regulatory operations at Cephalon Inc., a drug company in Frazer, Pa.

Merck was compelled to withdraw Vioxx last Sept. 30, after one of its own studies revealed the increased cardiovascular risk. Up to that time, the company had steadfastly defended Vioxx's safety in the face of growing published analysis of the potential for risk. Another Cox-2 inhibitor, Pfizer Inc.'s Celebrex, remains on the market with heavy warnings about heart risks -- and sharply lower sales.

The jurors in the Merck trial said they were deeply troubled by internal documents suggesting the company had suspected but suppressed the risk of Vioxx leading to heart attacks, even as it pushed the medicine in high-profile ad campaigns. "When you take a pill and put a pill in your mouth, you're taking a risk," said juror Stacy Smith, 21 years old. "We're trusting that the company has put out all those risks that there are."

Following the withdrawal of Vioxx, politicians called on the FDA to explain why this and other drugs were approved, and questioned whether the agency had put enough weight on publicly highlighting drugs' problems. In response, the FDA has said it will change how -- and when -- it discloses the possible risks of new drugs. The agency has become more aggressive in making its concerns public even before the link between a drug and a side effect is clear, and plans to do more in this area through a proposed "Drug Watch" Web site.

The FDA has also called for stronger warnings on the labels of a number of high-visibility drugs, and it forced some other medicines off the market over safety worries, including the painkillers Bextra from Pfizer and Palladone from Purdue Pharma LP.

Vioxx jurors complained after their vote that labels and communications from drug companies were incomprehensible. "Give us the chance to decide our own fate," said juror Derrick Chizer, 43, a service representative for the Social Security Administration. "Give us in layman's terms what the drug can do to us. Let us decide."

Chris Viehbacher, president of GlaxoSmithKline PLC's U.S. pharmaceuticals group, said the company is already feeling the effects of a "conservative swing" at the FDA, and the emphasis on risk avoidance has rippled through the company's research operations.

"You find the goalposts have shifted 10 years after you started developing a drug," he said, complicating or delaying studies of new medicines.

The FDA insists there has been no slowdown in approval of new drugs. An agency analysis found that the median number of months for standard approvals dropped slightly for drugs approved in the first six months of 2005 versus the same period last year -- to 10.4 months from 12.3 months.

The FDA's analysis "doesn't show any increase in review and approval times," said Scott Gottlieb, an FDA deputy commissioner. "Clearly the environment is more focused on drug-safety issues than in recent memory, but these issues were always front and center on the minds of FDA's review staff."

But the FDA's measures probably don't yet reflect the long-term effects the industry sees, which executives say are playing out in the votes of agency advisory committees and the feedback FDA reviewers are giving now for new products in their pipelines.

Glaxo, at the FDA's request, has suspended patient tests of an experimental drug to treat multiple sclerosis while the agency assesses the problems with Tysabri, a new MS drug withdrawn from the market by Elan Corp. and Biogen Idec Inc. early this year after several patients taking the medicine died. The FDA's request of Glaxo "was fairly unprecedented and an indication they're taking a more cautious approach," Mr. Viehbacher said.

More caution will affect how fast patients get access to new medicines, Mr. Viehbacher added. Eventually, patients will start to complain. "It's not as loud now because of the low R&D productivity the industry has. There aren't that many drugs that are being held up," he said.

At Schering-Plough, a product-leadership board -- made up of executives from R&D, sales, marketing and manufacturing -- meets to discuss each compound in development. On safety issues, "there is much more robust discussion on each compound than there was two years ago," says Mr. Hassan, the company's chairman, who also sits on the product-leadership board. One area of concern: whether the FDA will require a clinical trial that will track deaths and take five years to complete, delaying a new drug's coming to market. "If that is the case we have to decide if it's worth pursuing," Mr. Hassan says.

Further evidence of regulatory concerns over risk could emerge during the first week of September when FDA advisory committees will examine the applications of three drugs -- an inhaled insulin powder for diabetics from Pfizer and Sanofi-Aventis SA and Nektar Therapeutics Inc., and rheumatoid-arthritis and diabetes remedies from Bristol-Myers Squibb Co.

The development of a form of insulin not needing injection has been a hope of diabetics for decades. But regulators are expected to closely scrutinize that drug's side effects.

The Vioxx case also reinforces other industry trends that were emerging before the drug was pulled. Several drug companies, including Bristol-Myers and Novartis AG, are pulling back from research on drugs sold broadly to general practitioners, and focusing on specialty areas like cancer drugs; the public's tolerance for risk is higher for potentially life-saving cancer drugs than for painkillers like Vioxx.

"Developing drugs for primary care is becoming less attractive to the industry," said Arthur Higgins, chairman of Bayer Healthcare. The Bayer AG unit has shifted away from primary-care medicines to specialty areas like cancer.

Pfizer, known for its sweeping franchise of drugs for primary care, bet big on Cox-2s, and executives there remain hopeful that Celebrex will someday rebound. With Vioxx and Bextra off the market, Celebrex is the only choice for most patients seeking pain relief from a Cox-2 medicine. Yet sales of Celebrex remain sluggish at $813 million world-wide for the six months ended in June, compared with $1.5 billion in the same period a year ago. Sales of Bextra amounted to just $14 million during first half of the year, compared with $545 million during the same period in 2004.

As a result, the Pfizer Cox-2 franchise, the main reason the company paid nearly $60 billion for Pharmacia Corp. in 2003, has been cut by more than half in a year's time. Meanwhile, Merck's Arcoxia, a Cox-2 available only in selected markets outside the U.S., garnered a paltry $230 million in world-wide sales last year.

While Novartis, the Swiss drug giant, and Glaxo continue to develop Cox-2 medicines of their own, the sales outlook for the drugs has been reduced rather than boosted by the removal of rival pills under a safety cloud. After years of touting Prexige as a coming blockbuster, Novartis has lowered expectations for the product, which has been approved by the United Kingdom, but not sold there. In the U.S., Prexige is stalled at the FDA, which requested additional data on the drug's safety profile. Glaxo's Cox-2 drug, still designated by number as Compound 406381, has progressed only to midstage clinical tests.

Over time, Schering-Plough's Mr. Hassan expects there will be a better balance of benefit and risk. "The baby boomers are getting older and this is a population that has grown used to getting a lot," he says. "There is going to be a huge demand from the market to continue to bring more-innovative products to the market."

Write to Scott Hensley at scott.hensley@wsj.com⁸, Paul Davies at paul.davies@wsj.com⁹ and Barbara Martinez at Barbara.Martinez@wsj.com¹⁰