[e-drug] drug companies and regulators in the spotlight

["E-Drug" <e-drug@healthnet.org>]

E-DRUG: drug companies and regulators in the spotlight
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[the SSRI and Cox-2 scandals are piling up - time to review the way society controls its medicines! Should Drug Regulators be paid mostly by industry fees (as currently is the case), or rather from general tax? Drug regulators are supposed to protect public health, isn't it? So why are they getting so close with industry? Who will otherwise protect us from profit driven drug companies? Here is a series of news articles from the BMJ. Crossposted with thanks from Druginfo. Copied as fair use. WB]

http://bmj.bmjjournals.com/cgi/content/full/329/7472/937 
BMJ  2004;329:937 (23 October), doi:10.1136/bmj.329.7472.937 
Consumer organisations criticise influence of drug companies 
Zosia Kmietowicz 
London 

The pharmaceutical industry operates in a way that puts profits before public health, members of parliament (MPs) heard last week. And the regulatory authorities, which are meant to ensure the safety of drugs and protect the public, collude with the industry, they were told. 

Testimonies from five doctors and two consumer champions, who were being questioned by the health select committee for its inquiry into the influence of the pharmaceutical industry, built a picture of an industry that creates health anxieties among the public to boost its profits. 

At the same time, withholding unfavourable trial results and controlling what research gets published ensures that doctors get the messages that companies want to promote, the committee heard at the second public sitting of its inquiry. 

Public awareness campaigns are part of a "multipronged marketing approach" that are commonly employed by drug companies to "gain further control over what medicines are being prescribed and to whom," said Graham Vidler, head of policy at the consumer organisation Which?, formerly known as the Consumers' Association. 

"These can often be for quite trivial conditions, such as toenail infections, and they encourage patients to go and see their general practitioner, often in quite strong terms," said Mr Vidler. "At the same time the industry will be advertising drugs to these GPs, and our research shows that GPs often take the path of least resistance and say yes to patients and prescribe the drug even though they feel it may not be the most appropriate thing to do." 

GPs can see pharmaceutical representatives on a daily basis, and their influence can lead to changes in prescribing habits, said Des Spence, a GP in Glasgow and spokesman for the No Free Lunch campaign, a group of UK healthcare professionals concerned at the undue influence of the pharmaceutical industry on doctors in promoting drug products. 

"Within three or four years [of it being launched] Vioxx [rofecoxib] became 40% of the medicines we were using in my area," said Dr Spence. "The industry has a major influence on healthcare policy. The influence is across the field and affects doctors, nurses, patient organisations, and government agencies. The industry is active in all these fields and has a very clear agenda - that of profit - and that is in direct conflict with the responsibilities of the NHS." 

Part of the problem is that the industry is charged with policing itself through the Association of the British Pharmaceutical Industry, which is funded by drug companies, said Ike Iheanacho, editor of the Drug and Therapeutics Bulletin. 

"A regulatory body needs to punish companies that are responsible for misleading activities and tell people they have been misled. If these are the standards that we would like to see then they are largely absent from the present regulatory system," he said. 

David Healy, head of psychological medicine at the University of Cardiff, believes that research articles have a greater influence on doctors' prescribing habits than promotional activities. But again the process of publishing research is rife with pharmaceutical industry influence, he said. 

Professor Healy claimed that at least half of articles on drug efficacy that appear in the BMJ, the Lancet, and the New England Journal of Medicine are ghost-written by pharmaceutical companies and that "the most distinguished authors from the most prestigious universities" put their names to them without ever seeing the raw data. 

Peter Wilmshurst, a consultant cardiologist at Royal Shrewsbury Hospital, said that in the past he has been offered bribes by a pharmaceutical company not to publish unfavourable research results. Dr Wilmshurst also claims that he knew of three professors of cardiology who were told their results were aberrant and were persuaded by the pharmaceutical company who had sponsored the study not to publish. 

"I suspect this is as common now as it ever was," said Dr Wilmshurst. He also told the committee that key opinion leaders can be paid in the region of #5000 ($9000; E7000) for an hour's talk about a drug they have no experience of using, and their influence can have a big impact on practice. 

Dr Spence added, "The amount of hospitality received by doctors compared with other public services is a disgrace. If policemen, teachers, or MPs received this level of hospitality there would be a public outcry." 

Also giving evidence to the committee, Richard Brook, chief executive of the charity Mind, called for greater transparency in how the Medicines and Healthcare Products Regulatory Agency operates and for disclosure of any links between people working in the agency and people in the drug industry. 

Mr Brook resigned from the agency's expert group investigating the safety of selective serotonin reuptake inhibitors (SSRIs) after he discovered that the agency waited many years before disclosing the evidence about withdrawal effects of these drugs and their potential to pre-dispose children to suicide. 

Many of the agency's key personnel have longstanding links with the pharmaceutical industry and own shares in companies, said Mr Brook. "For a number of reasons I was very concerned that there was no robustness [at the agency]. We want to see a better way to do health research and people with consumer and legal interest serving on the agency," he said. 

Andrew Herxheimer, emeritus fellow at the UK Cochrane Centre, Oxford, called the relationship between the industry and the agency "a closed, inbred community where the industry is the client and the client must be looked after" and where a "culture of secrecy" permeates. 

He called for the reporting of adverse drug reactions to be separated from the business of licensing drugs. 

Witnesses also called for stronger enforcement of formularies in general practices, declaration by pharmaceutical companies of their contact with and payments to doctors, and regulation of the industry's influence on consumers. 

Commenting on Professor Healy's comments after the hearing, Dr Kamran Abbasi, acting editor of the BMJ, said: "The BMJ takes the issues of transparency and accountability very seriously. We believe that authors must accept full responsibility for the integrity of their research - including having the idea, collecting and analysing the data, interpreting the results, and writing the paper - and we have several policies in place to ensure this." 

~~~
http://bmj.bmjjournals.com/cgi/content/full/329/7472/935 
BMJ  2004;329:935 (23 October), doi:10.1136/bmj.329.7472.935 
US government agency to investigate FDA over rofecoxib 
Jeanne Lenzer 
New York 

The US Government Accountability Office, a regulatory watch-dog on federal government spending, is to investigate claims that the Food and Drug Administration attempted to silence one of its senior medical officers when he tried to warn that rofecoxib (Vioxx) caused heart attacks and strokes. 

The drug was withdrawn on 30 September by its manufacturers, Merck, after a study found a fourfold increase in serious thromboembolic adverse events in patients receiving rofecoxib compared with patients receiving placebo ( BMJ 2004;329: 816, 9 Oct). 

David Graham, associate director for science in the FDA Drug Center's Office of Drug Safety, said that he was subjected to "veiled threats" when he sent his report to superiors at the FDA, who wanted him to water down his findings. 

The Government Accountability Office has already launched a separate investigation into the FDA after another FDA expert, Andrew Mosholder, said his report warning of the risks of antidepressants for children was suppressed ( BMJ 2004;329: 307, 7 Aug). 

A spokesperson for the Government Accountability Office told the BMJ that it will now include Dr Graham's charges in their investigation and the agency will focus on the FDA's "handling of drug safety issues." The full scope of the investigation has not yet been determined, however, since "events continue to unfold," said the spokesperson. 

Senator Chuck Grassley of Iowa said in a news release that the FDA's attempts to silence Dr Graham led to the FDA sitting "on the sidelines while life threatening issues threaten the American public." 

In a letter of 15 October to the FDA, Mr Grassley asked, "Did the government agency that's supposed to regulate pharmaceuticals have an inappropriate agreement with Merck? And did a cosy relationship between the FDA and a pharmaceutical company allow a drug with known safety risks to stay on the market longer than it should have?" 

Eric Topol, chief of cardiovascular medicine at the Cleveland Clinic, Ohio, said that the FDA took a passive approach: "They were the first ones to uncover the issue. They knew about this as early as November 18, 1999, when the data and safety monitoring board alerted Merck there was a serious problem. They could have ordered a large trial but they didn't. As a result, anywhere from 20 000 to 160 000 people suffered heart attacks and strokes." 

The FDA responded to the BMJ with an email stating, "There was absolutely no undue pressure on Dr Graham. As a scientific agency, FDA values open discussion... the standard agency review process and procedure is a more rigorous peer review." 

Mr Grassley provided evidence of what he called the "cosy relationship" between the FDA and Merck by releasing a copy of an email from 12 August from Anne Trontell, deputy director of the FDA's Office of Drug Safety, in which she criticises Dr Graham's report and wrote that the FDA should notify Merck before Dr Graham's review became public "so they can be prepared for extensive media attention that this will likely provoke." 

~~~
http://bmj.bmjjournals.com/cgi/content/full/329/7472/935-a 
BMJ  2004;329:935 (23 October), doi:10.1136/bmj.329.7472.935-a 
Pfizer criticised over delay in admitting drug's problems 
Jeanne Lenzer 
New York 

Pfizer delayed announcing negative data about its painkiller valdecoxib (Bextra), Curt Furberg, a member of the US Food and Drug Administration's Data Safety and Risk Management Advisory Committee, told the BMJ this week. When the company eventually presented its data to the FDA, it also left out important details, Dr Furberg alleges. 

Pfizer stood to gain by Merck's withdrawal of rofecoxib on 30 September, after reports linked the drug to increased heart attacks and strokes ( BMJ 2004;329: 816, 9 Oct). That gain was amplified when a major health insurer, BlueCross BlueShield, announced that they had added valdecoxib to their formulary after the withdrawal of rofecoxib. 

Pfizer initially defended valdecoxib, saying the drug was safe in patients with osteoarthritis and rheumatoid arthritis. But on 15 October the company issued a news release, qualifying its earlier statement. The release said, "In two trials in a high-risk surgery known as coronary artery bypass graft (CABG), an increase in cardiovascular events was observed in patients receiving Bextra" (www.pfizer.com). 

That news, said Dr Furberg, a member of the FDA's Data Safety and Risk Management Advisory Committee, should have been released earlier. Dr Furberg asked Pfizer, after the withdrawal of rofecoxib, to supply him with data regarding the cardiovascular effects of valdecoxib. "I was struck by what they excluded," he told the BMJ. "They did not mention either of two trials of cardiac surgery patients." 

The first of the two trials was published but in a manner that obscured the risks, according to Dr Furberg. He said, "They listed each [adverse] event individually and said the numbers were too small to analyse. But I added up heart attacks, strokes, and deaths and found a statistically significant fourfold increase over placebo." 

~~~
http://bmj.bmjjournals.com/cgi/content/full/329/7472/940-e 
BMJ  2004;329:940 (23 October), doi:10.1136/bmj.329.7472.940-e 
Drugs companies are defrauding healthcare systems, conference hears
London Lynn Eaton 

Pharmaceutical companies are among those deliberately defrauding healthcare systems throughout Europe, a conference in London heard this week. 

More than 150 delegates from 20 of the 25 European Union states attended the two day event looking at fraud and corruption across the European healthcare system. Although delegates considered everything from health tourism (where individuals from one country go to another to receive free or cheap health care) to how to identify fraud, a recurring concern was the blatant fraud by some drug companies. 

"In any country, pharmaceutical fraud is a big problem," said Marieke Koken-Vossestein, head of the department of claim control at the Zorgverzekeraars Nederland (a Dutch department that develops antifraud policies across all health insurance schemes in the Netherlands). 

The fraud can range from doctors claiming for work they have not done through to drug companies who bribe doctors by paying them for switching patients to a new drug. 

Professor Peter Schvnhvfer of the Institute of Pharmacology, Bremen, said the fraud included not being able to view data from clinical trials submitted to the German regulatory body, the Federal Institute of Drugs and Medicinal Products. 

"If they have information they don't tell us it," he told the BMJ. "We don't have access to relevant data." 

That could mean therapeutic decisions were inappropriate - but because the relevant data were covered by a commercial confidentiality clause, those outside the institute could never know how appropriate the treatment was. 

He also cited what is euphemistically called a "drug use study," whereby a doctor is paid anything from 200 (#140; $250) to 500 for transferring a patient from one drug to another and then filling in a form to say what they have done. 

"We know that the pharmaceutical industry in German has spent 1bn a year for such drug use studies. And it is not just in Germany. In Italy, GSK [GlaxoSmithKline] spent 28m over a 12 year period just for doctors to provide a signature." 

State investigations of bribery by drug companies are becoming increasingly common, with two cases in the last year alone (BMJ 2004;328:1333). 

In the United Kingdom tighter antifraud measures have led to ongoing legal action against the manufacturers of warfarin and penicillin. 

Jim Gee, chief executive of the Department of Health's NHS Counter Fraud and Security Management Service, said they had evidence to suggest the existence of a price fixing cartel. Six pharmaceutical companies are allegedly involved in fixing the price of warfarin, costing the NHS #28m; seven are allegedly involved in keeping the price of penicillin high, costing the NHS #30m. 

The Serious Fraud Office has yet to decide whether criminal action should be pursued on these cases, and the civil cases have yet to be heard. 

The NHS Counter Fraud Service is also pursuing a further #100m for alleged price fixing of a generic version (ranitidine) of Zantac when the patent for that drug expired. 

"Clearly these companies operate in the other countries too," Mr Gee said, suggesting that other European countries might also have been similarly defrauded. 

Mr Gee said the NHS had done a great deal to try to tackle fraud and that although other countries had health insurance based systems, from what those delegates had told him, the level of fraud was as bad, if not worse.