Editorial

Is there a cure for corporate crime in the drug industry?

BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f755 (Published 6 February 2013) Cite this as: BMJ 2013;346:f755 1. Courtney Davis, senior lecturer in sociology, 2. John Abraham, professor of sociology Author Affiliations 1. courtney.davis@kcl.ac.uk; J.W.Abraham@sussex.ac.uk

Effective enforcement of regulations requires more resources and determination to impose robust sanctions Nearly 30 years ago, Braithwaites Corporate Crime in the Pharmaceutical Industry showed that unethical and corrupt behaviour was endemic in the sector. Sadly, there is growing evidence that little has changed. Recent research suggests that violation of the law continues to be widespread. Most new medicines offer little or no therapeutic advantage over existing products, so promotion plays a huge role in achieving market share. In a crowded and competitive marketplace the temptation for companies to resort to misleading claims is great. According to Gtzsche (doi:10.1136/bmj.e8462),1 as of July 2012, nine of the 10 largest drug companies were bound by corporate integrity agreements under civil and criminal settlements or judgments in the United States. The corporate activity that has led to recent government investigations has involved unethical and unlawful practices that are well beyond mere administrative offences. Whistleblowers and other insider accounts in the US typically include allegations that companies systematically planned complex marketing campaigns to increase drug sales, which involved illegal and fraudulent activities. These included active promotion of off label, or otherwise inappropriate, use of drugs, despite company knowledge that such use could seriously harm patients.2 3 How successful, then, have governments responsible for protecting citizens been in curbing illegal activity by the transnational research based drug industry? The recent introduction of Regulation 658/2007 in the European Union empowers the EU Commission to impose financial penalties for corporate violation of EU legislation on medicines. However, this may be too little, too late. Multi-million dollar fines imposed under US settlements seem to have failed to deter companies from violating regulations, given that several companies are repeat offenders. This has led to calls for sanctions to be strengthened. Imposing bigger fines is one option, but courts might be reluctant to impose penalties that would threaten the financial survival of companies. Other sanctions being debated include removing companies patent rights and holding senior managers criminally liable.4 Corporate integrity agreements could also serve as more effective vehicles for corporate probation by imposing escalating restrictions on company freedom appropriate to the offences committed. For instance, if companies hide clinical trial data, regulators could take over control of future clinical trials and charge offending companies for the cost of doing so. Although stronger sanctions are needed to deter drug companies from wrongdoing, this may be insufficient to protect the public because legal resolution of complex criminal and civil investigations takes years, during which time unethical and illegal behaviour may continue unabated. For example, during all phases of the US Justice Departments seven year investigation of Warner- Lamberts promotion of the drugs unapproved use, off label prescriptions for gabapentin (Neurontin) increased dramatically, which has raised suspicions that the firms off label promotion persisted throughout. 5 WarnerLambert, of which Pfizer is a parent company, pleaded guilty to charges of promoting gabapentin for the non-approved use. It was subsequently established that gabapentin was not efficacious for the non-approved indication, meaning that patients were exposed to the potentially harmful side effects of a drug when there was no scientific evidence to support a therapeutic effect in the condition for which it was prescribed.

In such cases, prompt action by regulatory agencies to prohibit further violation of the law is also needed to protect public health. However, it is striking that the Food and Drug Administration has played a marginal role in detecting cases of fraud or enforcing compliance with the law. Of the 11 civil or criminal cases involving off label promotion by major drug companies settled by the US Justice Department between 2003 and 2007, none was referred by the FDA.6 In the United Kingdom, the Medicines and Healthcare Products Regulatory Agency (MHRA) initiated 101 prosecutions for breaches of medicines legislation between 2005 and 2012, but none involved a large research based drug company. In addition, there was only one (unsuccessful) referral for potential prosecution of such a companyGlaxoSmithKline regarding paroxetine (Seroxat).7 Why have drug regulatory agencies played such a small role in prosecuting large companies given the evidence of extensive illegal activity uncovered in recent cases in the US that were brought by other prosecuting or investigating bodies? The reality is that, with current resources, medicines regulators can police only a fraction of the industrys ever expanding promotional activities. The MHRA currently vets print advertisements for around 50 medicinal products each year.8 Because of the complex and varied ways in which companies promote their drugs,2 gathering evidence of systematic illegal marketing requires far greater commitment in terms of time, money, and human capital. Increased resources and expanded legal authority may need to be backed up by a more probing regulatory culture. Both the MHRA and the FDA claim that they can generally achieve compliance through informal communication and negotiation with large firms, but regulators seem to treat evidence of non-compliance as isolated incidents rather than signals that firms may be engaged in extensive offending. Indeed, US government investigations indicate that even when faced with evidence of serious wrongdoing or persistent violation the FDA may be reluctant to initiate formal investigations or escalate its response against individual companies.6 9 Such timid regulatory behaviour may be symptomatic of the extent to which regulators have been encouraged by governments to be responsive to the commercial interests of industry and to view large drug firms as clients whose fees increasingly fund these agencies.10 There are some signs that change is afoot in the US, with additional funding granted for FDA fraud detection and prosecution alongside other signals from Congress that the agency should increase its enforcement activity.11 A similar shift in the UK is less likely given successive governments determination to reduce burdens on business. Whether government authorities in the EU are willing to take enforcement action against large drug companies will become clearer on resolution of the European Medicines Agencys investigation of Roche for safety reporting violations 12 and a French manslaughter investigation o f Servier Laboratories former president in relation to the antidiabetes drug, benfluorex (Mediator).13 Individual instances of corporate malfeasance are indicative of wider systemic problems. Whether companies continue to get away with it depends, in part, on whether regulators can develop credible systems of detection, enforcement, and punishment.

Notes

Cite this as: BMJ 2013;346:f755

Footnotes
Personal view, doi:10.1136/bmj.e8462 Competing interests: Both authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Provenance and peer review: Commissioned; not externally peer reviewed.

References
1. Gtzsche PC. Big pharma often commits corporate crime, and this must be stopped. BMJ2012;345:e8462. FREE Full Text 2. Kesselheim AS, Mello MM, Studdert DM. Strategies and practices in off-label marketing of pharmaceuticals: a retrospective analysis of whistleblower complaints. PLoS Med2011;8:1-9. 3. US Department of Justice. GlaxoSmithKline to plead guilty and pay $3 billion to resolve fraud allegations and failure to report safety data. 2012. Press release. www.justice.gov/opa/pr/2012/July/12-civ-842.html. 4. Kennedy K. Experts seek alternatives to excluding drug companies. USA Today2012 March 5. http://usatoday30.usatoday.com/news/washington/story/2012-03-05/penaltiesdrug-companies/53372918/1. 5. Kesselheim AS, Darby D, Studdert DM, Glynn R, Levin R, Avorn J. False Claims Act prosecution did not deter off-label drug use in the case of Neurontin. Health Affairs 2011;30:2318-27. FREE Full Text

6. US Government Accountability Office. FDAs oversight of the promotion of drugs for off-label uses. 2008, GAO-08-835. www.gao.gov/products/GAO-08835. 7. Medicines and Healthcare Products Regulatory Agency. MHRA investigation into Glaxosmithkline/Seroxat. 2008. www.mhra.gov.uk/home/groups/espolicy/documents/websiteresources/con014155.pdf. 8. Medicines and Healthcare Products Regulatory Agency. Delivering high standards in medicines advertising regulation. Sixth annual report JanuaryDecember 2011. www.mhra.gov.uk/home/groups/commsic/documents/websiteresources/con143738.pdf. 9. US Committee on Energy and Commerce, House of Representatives. Ketek clinical study fraud: what did Aventis know? 2008. www.gpo.gov/fdsys/pkg/CHRG-110hhrg48587/pdf/CHRG-110hhrg48587.pdf. 10. Abraham J, Davis C. Interpellative sociology of pharmaceuticals: problems and challenges for innovation and regulation in the 21st century. Technol Anal Strategic Manage2007;19:387-402. CrossRef 11. Skadden. FDA Revamps Criminal Prosecution Guidelines and Expands Health Care Fraud-Related Investigations. 2011. https://www.skadden.com/sites/default/files/publications/FDA_Revamps_Crimi nal_Prosecution_Guidelines_0.pdf. 12. European Medicines Agency. European Medicines Agency acts on deficiencies in Roche medicines-safety reporting. EMA/405725/2012. 2012. www.ema.europa.eu/docs/en_GB/document_library/Press_release/2012/06/WC 500129047.pdf. 13.

Reuters. France Servier founder investigated in drug deaths. 2012. www.reuters.com/article/2012/12/11/france-mediatoridUSL5E8NBGI520121211

Personal View

Big pharma often commits corporate crime, and this must be stopped
BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e8462 (Published 14 December 2012) Cite this as: BMJ 2012;345:e8462 1. Peter C Gtzsche, professor, Nordic Cochrane Centre, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark 1. pcg@cochrane.dk

When a drug company commits a serious crime, the standard response from the industry is that there are bad apples in any enterprise. Sure, but the interesting question is whether drug companies routinely break the law. I googled the names of the 10 largest drug companies in combination with the term fraud and looked for offences on the first page for each company. The most common recent crimes were illegal marketing by recommending drugs for non-approved (off label) uses, misrepresentation of research results, hiding data on harms, and Medicaid and Medicare fraud.1 All cases were related to the United States and involved huge settlements or fines, exceeding $1bn (620.6m; 769m) each for four companies. It was easy to find additional crimes committed by these same companies and committed outside the US.1 As the crimes were widespread and repetitive, they are probably committed deliberatelybecause crime pays. Pfizer, for example, agreed in 2009 to pay $430m to resolve charges related to illegal marketing of gabapentin (Neurontin), but as sales were $2.7bn in 2003 alone, and as about 90% was for off label use, such fines are far too small to have any deterrent effect. When Pfizer was fined $2.3bn for off label use of four other drugs, also in 2009, the company entered into a corporate integrity agreement with the US Department of Health and Human Services to detect and avoid such problems in future. Pfizer had previously entered into three such agreements in the past decade.2 Of the top 10 drug companies, in July 2012 only Roche was not bound by such an agreement. However, over 10 years in the 1990s, high level executives in Roche had previously led a vitamin cartel that, according to the US Justice Department, was the most pervasive and harmful criminal antitrust conspiracy ever uncovered.3 Roche

agreed to pay $500m to settle charges, equivalent to about one years revenue from its US vitamin business. Doctors are often complicit in these crimes, as kickbacks and other forms of corruption were common; they were induced to use expensive drugs and paid to lend their names to ghostwritten articles purporting to show that a drug works for unapproved conditions.1 The disconnect between the drug industrys proclamationsof the highest ethical standards, of following . . . all legal requirements, and providing most accurate information available regarding prescription medicines 4 5and the reality of the conduct of big pharma is vast. These proclamations are not shared by the companies employees or experienced by the public. An internal survey of Pfizer employees in 2001 showed that about 30% didnt agree with the statement, Senior management demonstrates honest, ethical behavior. 6 When 5000 Danes ranked 51 industries in terms of the confidence they had in them, the drug industry came second to bottom, beaten only by automobile repair companies. A US poll also ranked the drug industry at the bottom, together with oil and tobacco companies. The consequences of these crimes are huge, including the unnecessary deaths of thousands of people and many billions in losses for our national economies every year.7 As doctors have access only to selected and manipulated information, they believe drugs are far more effective and safe than they really are. Thus, both legal and illegal marketing leads to massive overtreatment of the population. In the US, the most sold class of drugs in 2009 (in US dollars) was antipsychotics. Antidepressants came fourth, after lipid lowering drugs and proton pump inhibitors. It is hard to imagine that so many Americans can be so mentally disturbed that these sales reflect genuine needs. It is time to introduce tougher sanctions, as the number of crimes, not the detection rate, seems to be increasing.8 Fines need to be so large that companies risk going bankrupt. Top executives should be held personally accountable so that they would need to think of the risk of imprisonment when they consider performing or acquiescing in crimes. To bring the crimes to light also outside the US, we need laws that protect whistleblowers and ensure they get a fair proportion of the fines. We also need to avoid the situation that, by settling accusations of crimes, drug companies can pretend they are innocent, which they often do. We also need laws requiring firms to disclose all knowledge about their drugs and research data,7 and laws that not only allow but require drug agencies to publish what they know, without hiding under some absurd proprietary nature of companies trial results clause, as happened with rosiglitazone 9with the consequence that the public was not informed that the drug causes myocardial infarction. Last but not least, doctors and their organisations should recognise that it is unethical to receive money that has been earned in part through crimes that have harmed those people whose interests doctors are expected to take care of. Many crimes would be impossible to carry out if doctors werent willing to participate in them. 1 10 11 12 13

Notes

Cite this as: BMJ 2012;345:e8462

Footnotes
Competing interests: the author has completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work. Provenance and peer review: Not commissioned; externally peer reviewed. A fuller account is at www.cochrane.dk/research/corporatecrime.

References
1. Gtzsche PC. Corporate crime in the pharmaceutical industry is common, serious and repetitive. 2013. www.cochrane.dk/research/corporatecrime. 2. Tanne JH. Pfizer pays record fine for off-label promotion of four drugs. BMJ2009;339:b3657. FREE Full Text 3. Barboza D. Tearing down the facade of Vitamins Inc. 10 Oct 1999. New York Times. www.nytimes.com/1999/10/10/business/tearing-down-the-facade-of-vitaminsinc.html. 4. Kelton E. More drug companies to pay billions for fraud, join the dishonor roll after Abbott settlement. 10 May 2012. Forbes. www.forbes.com/sites/erikakelton/2012/05/10/more-pharma-companies-to-join-thedishonor-roll-pay-billions-for-fraud-following-abbotts-settlement. 5. Pharmaceutical Research and Manufacturers of America (PhRMA). PhRMA code on interactions with healthcare professionals signatory companies. 11 June 2012. www.phrma.org/sites/default/files/108/signatory_companies_phrma_code_061112.p df.

6. Rost P. The whistleblower: confessions of a healthcare hitman. Soft Skull Press, 2006. 7. Gtzsche PC. Why we need easy access to all data from all clinical trials and how to accomplish it. Trials2011;12:249. CrossRefMedline 8. Almashat S, Preston C, Waterman T, Wolfe S; Public Citizens Health Research Group. Rapidly increasing criminal and civil monetary penalties against the pharmaceutical industry: 1991 to 2010. 16 December 2010. www.citizen.org/documents/rapidlyincreasingcriminalandcivilpenalties.pdf. 9. Cohen D. Rosiglitazone: what went wrong? BMJ 2010;341:c4848. FREE Full Text 10. Braithwaite J. Corporate crime in the pharmaceutical industry. Routledge, 1984. 11. Angell M. The truth about the drug companies: How they deceive us and what to do about it. Random House, 2005. 12. Kassirer JP. On the take: how medicines complicity with big business can endanger your health. Oxford University Press, 2005. 13. Newman M. Bitter pills for drug companies. BMJ2010;341:c5095. FREE Full Text Drug Regulation

Bitter pills for drug companies

BMJ 2010; 341 doi: http://dx.doi.org/10.1136/bmj.c5095 (Published 17 September 2010) Cite this as: BMJ 2010;341:c5095 1. Melanie Newman, reporter

Author Affiliations
1. melanienewman@tbij.com

After criticism that massive fines are failing to dissuade drug companies from engaging in fraudulent business practices, the US government is turning to more radical enforcement measures. Melanie Newman reports It was the biggest fine ever imposed in America, the largest healthcare fraud settlement in Department of Justice history, and the largest civil fraud settlement ever paid by a drug company. It was, said Kevin Perkins, assistant director of the Federal Bureau of Investigations criminal investigative division a clear message to drug companies that they would not be allowed to peddle their prescriptions or products for uses beyond their intendedand federal government-approvedpurpose. Pfizer had just agreed to be fined a record $2.3bn (1.5bn; 1.8bn) for illegally promoting four drugsvaldecoxib, ziprasidone, linezolid, and pregabalin for uses that the US Food and Drug Administration had not approved.1 The company was also accused of paying incentives or kickbacks to doctors to prescribe the drugs, a charge that was also resolved under the terms of the settlement. Both practices are considered fraudulent in the US, because they mean government healthcare programmes are paying for drugs that may not work effectively or are unnecessary. On the day after the fine was announced, the New York Times pointed out that $2.3bn amounted to less than three weeks of Pfizers sales. 2 And US authorities admitted that Pfizer was illegally marketing its drugs at the same time as it was negotiating settlement terms for a similar, previous offence.

Repeat offending and unenforceable penalties

In 2004 Pfizer agreed to pay $420m to settle charges that its newly acquired subsidiary, Warner-Lambert, had marketed an epilepsy drug, gabapentin, for unapproved purposes. The companys lawyers assured prosecutors that Pfizer and all its subsidi aries would cease this practice immediately. But at the same time its sales representatives were marketing the anti-inflammatory drug valdecoxib, which was approved for arthritis and menstrual pain, for other, unapproved conditions. And Pfizer is not alone in failing to change its behaviour in response to large fines. AstraZeneca paid out $520m in 2010 to settle civil charges of illegally marketing its anti-psychotic drug quetiapine.3 Seven years earlier it had been fined $355m for

criminal and civil charges relating to the same offence this time involving the prostate cancer drug gosarelin.4 So why are the fines not working? Critics argue that for the multibillion dollar drug industry, even such hefty fines are not hard pills to swallow. The penalties, they say, are treated as just another cost of doing business. Worse, as the companies make up their lost profits by hiking future drug prices, it is actually the public that ends up paying for them. Patrick Burns, communications director at the campaigning organisation Taxpayers Against Fraud, which helps whistleblowers to expose fraud against the government, complains that the fines have had little effect beyond moving a few numbers on the New York stock exchange. Pfizer made around $180bn out of the 12 drugs that were the subject of the federal investigation, he points out. They paid $2.3bnthats a good business plan. He adds: Were shooting 22slittle bullets into the arse of a rhino. Theyre roaring a little, running a little, and then theyre going back to business. If were going to affect change, we have to increase the calibre of the bullet. By settling the case, and thereby avoiding criminal conviction by a court, Pfizer also side stepped a rule that companies convicted of major fraud against the government should be barred from working for government programmes. Under a section of the US Social Security Act that came into force in 1996, any organisation convicted of healthcare fraud at state or federal level must be excluded from Medicare and state healthcare programmes. The law is one of a series of statutes introduced to strengthen the Department of Healths ability to puni sh fraud. Although Pfizer settled the case, the government could still have debarred the company. But the companys lawyers managed to wriggle free of these commercially damaging restrictions. A Pfizer subsidiary was permitted to plead guilty to the crimi nal charges,5 leaving the parent company free to continue working for the government. Mr Burns says that The problem with that portion of the law is that Pfizers too big to fail. There are too many people that use Pfizer drugs. Lewis Morris, chief lawyer at the US Department of Health and Human Services, suggests thats true. A big drug company hires tens of thousands of people, provides life saving drugs, its a critical component of the health system. Cutting them out of the market and depriving patients of drugs, putting a lot of innocent employees on the streetthats not a very attractive option.

New sanctions
But all this could be about to change, with major consequences for the drug industry. The government, reveals Mr Morris, is now turning to more radical measures that will make the stock market and the shareholders sit up.

In the drug industry we have a case that is moving to final resolution where we are going to be requiring a subsidiary, and all its assets, to be sold off to a third party, he says. The parent company can no longer own that part of the company. Its a radical move but one that the department has used before in a different area. In 2006 the Tenet Healthcare chain settled several civil fraud allegations for $900m.6 We found that in two different instances a particular hospital had paid kickbacks to doctors and had provided medically unnecessary cardiac services to patients. As part of resolving the allegations with the parent company, those two hospitals had to be sold off to an independent third party, Mr Morris says. Five years ago [before the Tenet case] people would have said youre never going to get a hospital [chain] to sell off an asset, youre never going to be able to force that kind of change. Confiscation of the companys patents is another penalty under consideration. If a company abuses a patent by marketing a drug for a purpose it has no t be approved or tested for, why should it continue to benefit from the exclusivity that you get as a brand name? Mr Morris asks. The company would be allowed to keep the drug but it would have to compete as a generic. That would have an enormous impact on the financial bottom line, and we think it would probably cause some of these executives to think twice about illegally marketing drugs.

Accountability
Even this, argues Burns, will not be enough unless executives are held personally accountable for their companies wrongdoing. The pain has to be personal, says Mr Burns. The US invaded Iraq for regime change, we invaded Afghanistan for regime change, we took over General Motors and forced a change at the top of the company its time we started to force a change at the top of certain healthcare corporations. We need to say: get rid of your chief executive, your finance officer, your compliance officer, or you are done with us. Mr Morris says the department is planning to make more use of a strict liability rule to hold executives to account. He explains: This responsible corporate official doctrine will allow us to go to a chief executive and say I dont even need to have proof that you specifically hatched this scheme. You could have stopped it. You had the responsibility and the authority to stop it and you didnt, so you have to leave the company. Executives found guilty will be banned from working for the state, and their sacking could be a condition of the companys negotiated settlement. Officials have already used this approach in a handful of cases. In 2007 the president, chief legal officer, and former chief medical officer of drug company Purdue Frederick pleaded guilty to charges of misbranding prescription painkiller OxyContin (modified release oxycodone) as part of a $634.5m settlement after the company had claimed that the drug was less addictive and less likely to be abused than rival medications.

That was strict liabilitythey did not admit to any personal engagement in the fraudulent conduct, Mr Morris says. Nonetheless, they were convicted of misdemeanour and excluded from our programme for 12 years. Consumer advocates have called for executives to be given jail terms. But Mr Morris argues that the criminal burden of proof is hard to meet. In white collar crime responsibility for illegal acts is usually spread across many individuals at all levels in the organisation: there is rarely one person who has made a critical decision on which the prosecutors can hang their case. Another of the departments relatively new lines of attack is to pursue individual doctors suspected of receiving kickbacks from industry in return for prescribing or using certain practices. A kickback can be as crass as twenty dollar bills in an envelope or something more subtleperhaps putting the doctor on an advisory committee where she doesnt do any work but gets paid $20000 or taking the doctor on all expenses paid trip to Phoenix, Arizona, in the winter, Mr Morris says. The medical profession is waking up to its responsibilities here. This July, Harvard Medical School banned its faculty from accepting industry sponsored travel and meals and from giving sponsored speeches. And in March, Stanford University extended its conflict policy to ban all adjunct faculty (volunteer teaching staff) from participating in drug company speakers bureaus. But enforcement is equally important, Morris says. And although the department has traditionally focused on the company offering the kickback, it is now turning its attention to the recipients the doctors. When a company is charged with paying kickbacks to doctors, the authorities won t accept a settlement unless the company cooperates with a secondary investigation into the doctors concerned. The company has to turn over the call notes . . . well know which doctors said to a drug rep, If you dont give me that $50 000 consulting agr eement Im moving all my artificial hip patients to your competitor, says Mr Morris. The Department of Healths Office of the Inspector General, where Mr Morris is chief counsel, has the right to impose a $50 000 penalty for every kickback received plus three times the amount of the kickback and exclude the doctor from working for the state again. Like drug companies, doctors usually settle the cases rather than allow them to continue to the exclusion stage. They still have to pay a substantial fine, but the department monitors their behaviour rather than throwing them out of state programmes. This February Florida based surgeon Harvey Montijo agreed to pay $650 000 after the Department of Health and Human Services alleged he solicited and received remuneration in the form of consulting payments from two medical device manufactures in exchange for using their orthopedic hip and knee products. 7

Will this combination of new measures convince companies, executives, and doctors that illegal behaviour is just too risky, even though the profits to be made are so huge? Its too soon to tell, as many of the fines currently being dished out are for offences that happened four or five years ago. But Mr Burns isnt convinced the deterren t is strong enough yet. In medieval times people used to put the bodies of criminals in cages and hang them to rot outside the town, he says. You would see the bones and youd know that if you committed a crime there, you werent going to be slapped aro und, you were going to be done. Thats the message we need to send to the people who are green-lighting the fraud, who think that fraud is a good business plan.

Notes
Cite this as: BMJ 2010;341:c5095

Footnotes
Competing interests: The author has completed the unified competing interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declares no support from any organisation for the submitted work; no financial relationships with any organisation that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work. The Bureau of Investigative Journa lisms documentary on the drug industry is available at http://thebureauinvestigates.com/2010/08/11/documentary-revealsthe-unhealthy-profits-of-the-pharmaceutical-industry/. Provenance and peer review: Commissioned; not externally peer reviewed.

References
1. US Department of Health and Human Services. Justice department announces largest health care fraud settlement in its history. 2 Sep 2009. www.hhs.gov/news/press/2009pres/09/20090902a.html. 2. Gardiner H. Pfizer pays $2.3 billion to settle marketing case. New York Times 2009 Sep 2. www.nytimes.com/2009/09/03/business/03health.html. 3.

US Department of Justice. Pharmaceutical giant AstraZeneca to pay $520 million for off-label drug marketing. Press release, 27 Apr 2010. www.justice.gov/opa/pr/2010/April/10-civ-487.html. 4. US Department of Justice. AstraZeneca pharmaceuticals pleads guilty to healthcare crime; company agrees to pay $355 million to settle charges. Press release, 20 June 2003. www.justice.gov/opa/pr/2003/June/03_civ_371.htm. 5. Griffin D, Segal A. Feds found Pfizer too big to nail. CNN2010 Apr 2. http://edition.cnn.com/2010/HEALTH/04/02/pfizer.bextra/index.html. 6. US Department of Justice. Tenet Healthcare Corporation to pay US more than $900 million to resolve false claims act allegations. Press release, 29 June 2006. www.justice.gov/opa/pr/2006/June/06_civ_406.html. 7. US Department of Health and Human Services. Kickback and physician self-referral. http://oig.hhs.gov/fraud/enforcement/cmp/kickback.asp.

Pfizer pays record fine for off-label promotion of four drugs

BMJ 2009; 339 doi: http://dx.doi.org/10.1136/bmj.b3657 (Published 9 September 2009) Cite this as: BMJ 2009;339:b3657 Health policy Health service research Biological agents Drugs: musculoskeletal and joint diseases

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Related content Article metrics 1. Janice Hopkins Tanne

Author Affiliations Pfizer, the worlds largest drug company, has agreed to pay $2.3bn (1.4bn; 1.6bn) to settle charges of fraud and civil and criminal liability over its promotion of off-label use of four drugs. The US Department of Justice said it was the largest healthcare fraud settlement in the departments history and the largest criminal fine ever. The New York Times noted that $2.3bn amounted to less than three weeks of Pfizer sales (www.nytimes.com, 3 Sep, Pfizer to pay $2.3 billion to settle inquiry over marketing). Unlike in previous settlements by drug companies, the announcement of the settlement was made at a Washington press conference by Kathleen Sebelius, secretary of the Department of Health and Human Services, the parent body of the Food and Drug Administration. Although the investigation was conducted under the Bush administration, the departments publicity suggests that the Obama administration will be tougher on drug companies that market their products for unapproved indications. In a press release Pfizer said that it had finalized a previously reported agreement in principle with the US Department of Justice to settle an investigation regarding past offlabel promotional activities related to four drugs. Pfizer said it had previously disclosed financial statements setting aside funds for the settlements. As part of the settlement with the justice department, Pfizer agreed for the fourth time not to do it again. Pfizer agreed to enter a corporate integrity agreement with the Office of the Inspector General of the Department of Health and Human Services to avoid and detect such problems. Pfizer previously entered three such agreements. The many charges related to Pfizer s promotion of the anti-inflammatory drug valdecoxib (marketed in the United States as Bextra) and other drugs for uses not approved by the FDA. US doctors may prescribe any drug approved by the FDA for any indication, but drug companies may not promote off-label use. The Pfizer subsidiary Pharmacia & Upjohn agreed to plead guilty to a felony violation of the Food, Drug and Cosmetic Act and to pay fines and forfeitures amounting to $1.3bn. The subsidiary had promoted valdecoxib for off-label uses and at dosages that the FDA had not approved. The drug, a cyclo-oxygenase-2 inhibitor, was withdrawn from the market in 2005. In addition, Pfizer agreed to pay $1bn to resolve charges that it promoted off-label uses of valdecoxib and also ziprasidone (Geodon), an antipsychotic drug; linezolid (Zyvox), an antibiotic; and pregabalin (Lyrica), an anti-epilepsy drug.

Pfizers promotion of off-label use of these drugs caused doctors to prescribe them and thus to submit false claims to the US governments Medicare insurance programme for elderly people and its Medicaid programme for poor people when these drugs were not approved. Of the $2.3bn payment, $1bn will return funds to Medicare, Medicaid, and other government insurance programmes. States that share Medicaid payments with the government will receive part of that $1bn. Six whistleblowers, including a former Pfizer salesman who quit, will share $105m. Also, $635m will go to the Victim Witness Fund, which supports state programmes helping crime victims and is entirely funded from fines and penalties collected by state and federal authorities. The rest will go to the Treasury Department.

Notes
Cite this as: BMJ 2009;339:b3657