Drug firms lagging on openness
Despite vow, few studies publicized
Six months after the drug industry vowed to make its clinical trials more transparent, and three months after launching a common website to give the public ''unprecedented access" to studies both good and bad, drug companies have posted unpublished trial results on the site for just five drugs.
Pfizer Inc., the world's largest drug manufacturer with $40 billion in revenues in 2003, voluntarily disclosed unpublished study results on only one of the 29 prescription brand-name drugs it actively markets in the United States, the antidepressant Zoloft.
Merck & Co. posted a listing for its withdrawn painkiller Vioxx, but clicking on the link reveals nothing but another link to the product's label and a list of two previously published studies, but not the studies themselves. There is no information posted, for example, about an unpublished, large-scale clinical trial of Vioxx performed in 2000 that showed a six-fold increase in cardiovascular risk. That study has been cited, among others, by critics who say Merck and the Food and Drug Administration ignored risks of Vioxx years ago.
The lack of information comes amid heightened public concern about drugs similar to Vioxx, such as Pfizer Inc.'s Celebrex and Bextra. Pfizer has not posted any information on Celebrex or Bextra. A spokeswoman declined to say when the company would post past studies or if unpublished data on the heavily prescribed drugs even exist.
''It's pathetic," said Dr. Drummond Rennie, associate editor of the Journal of the American Medical Association and an advocate for mandatory disclosure of all clinical trial results. ''They get all the publicity from saying they will do it, and then they don't."
A Globe review of websites indicates that the voluntary approach has produced limited disclosures thus far. Last year's commitment by members of the Pharmaceutical Research and Manufacturers of America, the industry's Washington lobbying organization, has resulted in a total of 26 drugs listed on the clinical trials results website (www.clinicalstudyresults.org). That is out of a total of more than 10,800 prescription medications and dosages sold in the United States.
Of the 26 drugs listed, just five contain data that have been previously unpublished, according to the Globe review.
The majority of the remaining 21 drugs on the website contain listings of scientific papers that were already published in medical journals and have been available to physicians.
Some legislators, physicians, editors of academic medical journals, and consumer groups said the snail's pace of voluntary disclosure is all the more reason Congress this session should craft laws to require that companies disclose all information to the public about potentially life-threatening side effects hidden in America's drug supply.
''The drug companies just hide the negative results and hope the public can't seek them out," said US Representative Edward J. Markey, a Massachusetts Democrat and sponsor of one of several initiatives in Congress that would make disclosures of clinical trial data mandatory
''It's set up a like a poker game. The less information you give, the more likely you are to make money," he said.
Last week, the industry launched an initiative for an international disclosure database and pledged to list the launch of more clinical trials on a National Institutes of Health website. The announcements were the latest of at least four announcements since last June about increasing the volume of voluntary disclosures.
''These sporadic, inconsistent, partial responses by a few companies have to be viewed as thinly disguised public relations efforts," said Dr. Sidney Wolfe, director of the health research group Public Citizen, a Washington consumer group that has joined the call for mandatory disclosure of trial results.
But drug company representatives said the work is proceeding as intended. At the height of the industry's political crisis last September, its lobbying group said it would take a full year for all results to be posted. PhRMA also said it would post data from trials completed after October 2002, although in practice much of the data posted thus far precede that date.
''The progress has been fine. We gave people a full year to post things, and the companies are taking that very seriously," said Dr. Alan Goldhammer, associate vice president for regulatory affairs for PhRMA. He said he expected the pace of postings to increase this year as drug companies compile data.
Companies generally keep the existence of unpublished studies secret. Companies notify the FDA if a trial is performed in the United States, but the data generally only have to be made public if they are part of the FDA application for an approved drug.
Such rules make estimating the amount of unpublished data from clinical trials difficult if not impossible, said editors of medical journals and consulting firms expert in the field.
Rennie estimated in a July 2003 study that 1 million late-stage, controlled clinical trials had been conducted since 1948, and that only half the results were ultimately published, although many may have been presented as a poster or paper at scientific conferences. Getting a grip on the universe of unpublished data is one of the goals of Rennie and other advocates of mandatory disclosure.
Most of the world's 10 largest drug companies, with collective annual revenues over $200 billion, either said last week said they did not know how many drugs they would ultimately post on the common US website, or they did not respond to the question. PhRMA officials said they were unable to quantify how much data can be expected to be revealed.
Drug companies said they were taking so long to publicly post information because they are taking raw data from unpublished studies and placing them into an internationally recognized, uniform format.
A Pfizer spokeswoman, Alison Lehanski, said disclosing trial results is a ''massive undertaking" that takes considerable time. Pfizer has established a team of workers to cull through studies, pull together information, make sure it fits in the PhRMA website guidelines, and make sure its postings are of ''very high quality," she said.
Merck has not posted the unpublished Vioxx trial from 2000 because the PhRMA site's voluntary guidelines only call for posting data completed after October 2002, said Merck spokesman Chris Loder. ''Given the voluminous nature, we did not go back and post trials completed prior to '02," he said.
Academics and physicians for several years had been pushing for more clinical trial disclosures before the issue gained momentum in 2004 when New York Attorney General Eliot Spitzer sued GlaxoSmithKline. Spitzer alleged that the British drug giant suppressed safety concerns about the effects of its antidepressant Paxil in children and adolescents. GlaxoSmithKline settled for $2.5 million in August 2004 without admitting wrongdoing.
The FDA -- after reviewing data from trials of Paxil and other antidepressants -- subsequently required in October that all antidepressants contain a ''black box warning" on their label disclosing slightly increased risk of suicidal thinking among young people taking the widely prescribed drugs.
In cases where drugs present specific dangers, the FDA requires black box warnings to alert physicians to particularly high risk of drug side effects in some patient populations.
The New England Journal of Medicine and other prominent medical journals, meanwhile, said they will require that drug companies disclose the launch of all drug studies as a condition of publication of the eventual results. The requirement, to take effect in July, will allow physicians and the public to at least be aware of every study being conducted.
The medical journals stopped short of requiring disclosure of the information gleaned from those trials.
Members of Congress, including Markey in the House and Democratic Senators Edward M. Kennedy of Massachusetts and Chris Dodd of Connecticut, introduced legislation to make trial disclosures mandatory. Republican Charles Grassley of Iowa, chairman of the Senate Finance Committee, is considering similar legislation.
Some of the initiatives in Congress could lead to the expansion of an existing National Institutes of Health website that lists current clinical trials for life-threatening diseases, ClinicalTrials.gov, to include details of the trial outcomes.
In response to all the pressure, a PhRMA representative told a congressional panel in September that the industry had a ''commitment to transparency."
The industry said it would disclose results of late-stage ''hypothesis testing" trials completed since October 2002, including trials for drugs that have already been approved but which drug companies have continued to test for potentially new uses. The industry has said it envisions the site as containing mostly information about late-stage and post-market clinical trials in which both effectiveness and safety are tested in large populations.
Individual players in the industry have taken a variety of approaches to the website. The third-largest drug company in the world, for example, the newly merged Sanofi-Aventis, hasn't decided what to do.
''We don't have a defined policy on that yet," said spokesman Marc Greene.
Lilly meanwhile, is focusing most of its efforts on creating a website of its own. GlaxoSmithKline has yet to post information about Paxil, the drug that was the focus of controversy, on the PhRMA website, although it does have extensive disclosures for Paxil on its own company website. To further complicate matters, GlaxoSmithKline has posted information on two other drugs on PhRMA's common website.
The presentation of individual drugs on the common website falls short of industry promises for a central, easy-to-use location to find critical health information, said Dr. Jeffrey Drazen, the editor in chief of the New England Journal of Medicine.
''It's not like they fit into a template," he said. ''Everyone's kind of putting stuff in their own way. You don't know where to look, and you might miss something."
The industry's performance thus far, he added, ''is not at all surprising. Their past behavior suggests that would be a legitimate reason for what's going on right now."
Christopher Rowland can be reached at firstname.lastname@example.org.