Bad Pharma

Bad Pharma
Author(s)	Ben Goldacre
Genre(s)	Science writing, medicine, investigative journalism
Publisher	Fourth Estate (UK), Faber & Faber (US)
Publication date	25 September 2012
Pages	430 (first edition)
ISBN	978-0-00-735074-2
Preceded by	Bad Science

Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients is a book by British physician and academic Ben Goldacre about the pharmaceutical industry, its relationship with the medical profession, and the extent to which it controls academic research into its own products. The book was first published in September 2012 in the UK by the Fourth Estate imprint of HarperCollins. It was published in the United States in February 2013 by Faber and Faber.

Goldacre argues in the book that "the whole edifice of medicine is broken," because the evidence on which it is based is systematically distorted by the pharmaceutical industry. He writes that the industry finances most of the clinical trials into its products, that it routinely withholds negative data, that trials are often conducted on small groups of unrepresentative subjects, that it funds much of doctors' continuing education, and that apparently independent academic papers may be planned and even ghostwritten by pharmaceutical companies or their contractors, without disclosure. Goldacre calls the situation a "murderous disaster," and makes a number of suggestions for action by patients' groups, physicians, academics and the industry itself.

The Association of the British Pharmaceutical Industry, the trade association in the UK for pharmaceutical companies, issued a statement arguing that the examples the book offers are "historical," that the concerns have been addressed, that the industry is among the most regulated in the world, and that it discloses all data in accordance with international standards.

Author

Ben Goldacre

Goldacre graduated in 1995 with a first-class honours degree in medicine from Magdalen College, Oxford, obtained an MA in philosophy from Kings College London, and undertook clinical training at UCL Medical School, qualifying as a medical doctor in 2000 and as a psychiatrist in 2005. As of 2012 he is Wellcome research fellow in epidemiology at the London School of Hygiene and Tropical Medicine.

Goldacre is known for his "Bad Science" column in The Guardian, which he has written since 2003, and for his first book, Bad Science (2008). This unpicked the claims of certain forms of alternative medicine, and criticized certain physicians and the media for a lack of critical thinking. It also looked at the MMR vaccine controversy, AIDS denialism, the placebo effect and the misuse of statistics.

Synopsis

The book contains an introduction, six chapters – "Missing Data," "Where Do New Drugs Come From?", "Bad Regulators," "Bad Trials," "Bigger, Simpler Trials," and "Marketing" – and an afterword, "Better Data."

Introduction

Goldacre writes in the introduction that the book aims to defend the following paragraph:

Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques which are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer. When trials throw up results that companies don't like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug's true effects. Regulators see most of the trial data, but only from early on in a drug's life, and even then they don't give this data to doctors or patients, or even to other parts of government. This distorted evidence is then communicated and applied in a distorted fashion. In their forty years of practice after leaving medical school, doctors hear about what works through ad hoc oral traditions, from sales reps, colleagues or journals. But those colleagues can be in the pay of drug companies – often undisclosed – and the journals are too. And so are the patient groups. And finally, academic papers, which everyone thinks of as objective, are often covertly planned and written by people who work directly for the companies, without disclosure. Sometimes whole academic journals are even owned outright by one drug company. Aside from all this, for several of the most important and enduring problems in medicine, we have no idea what the best treatment is, because it's not in anyone's financial interest to conduct any trials at all. These are ongoing problems, and although people have claimed to fix many of them, for the most part they have failed; so all these problems persist, but worse than ever, because now people can pretend that everything is fine after all.

"Missing Data"

In "Missing Data," Goldacre argues that the clinical trials undertaken by drug companies routinely reach conclusions favourable to the company. For example, in 2007 researchers studied every published trial on statins, drugs prescribed to reduce cholesterol levels. In the 192 trials that were studied, industry-funded trials were 20 times more likely to produce results that favoured the drug.

He writes that these positive results are achieved in a number of ways. Sometimes the industry-sponsored studies are flawed by design (for example by comparing the new drug to an existing drug at an inadequate dose), and sometimes the patients are selected to make a positive result more likely. In addition, the data is studied as the trial progresses, and if the trial seems to be producing negative data it is stopped prematurely and the results are not published, or if it is producing positive data it may be stopped early so that longer-term effects are not examined. He writes that this publication bias, where negative results remain unpublished, is endemic within medicine and academia. As a consequence, he writes, doctors may have no idea what the effects are of the drugs they prescribe.

An example he gives of the difficulty of obtaining missing data from drug companies is that of Tamiflu, manufactured by Roche to reduce the complications of bird flu. He writes that governments have spent billions of pounds stockpiling this, based in large part on a meta-analysis that was funded by the industry. He charts the efforts of independent researchers, particularly Tom Jefferson of the Cochrane Collaboration Respiratory Group, to gain access to information about the drug.

"Where Do New Drugs Come From?"

In the second chapter, the book describes the process as new drugs move from animal testing through phase 1 (first-in-man study), phase 2, and phase 3 clinical trials. Phase 1 participants are referred to as volunteers, but in the US are paid $200–$400 per day, and because studies can last several weeks and subjects may volunteer several times a year, earning potential becomes the main reason for participation. Participants are usually taken from the poorest groups in society, and outsourcing increasingly means that trials may be conducted in countries with highly competitive wages by contract research organisations (CROs). The rate of growth for clinical trials in India is 20 percent a year, in Argentina 27 percent, and in China 47 percent, while trials in the UK have fallen by 10 percent a year and in the US by six percent.

The shift to outsourcing raises issues about data integrity, regulatory oversight, language difficulties, the meaning of informed consent among a much poorer population, the standards of clinical care, the extent to which corruption may be regarded as routine in certain countries, and the ethical problem of raising a population's expectations for drugs that most of that population cannot afford. It also raises the interesting question of whether the results of clinical trials using one population can invariably be applied elsewhere. There are both social and physical differences: Goldacre asks whether patients diagnosed with depression in China are really the same as patients diagnosed with depression in California, and notes that Oriental people metabolize drugs differently from Westerners.

There have also been cases of available treatment being withheld during clinical trials. In 1996 in Kano, Nigeria, the drug company Pfizer compared a new antibiotic during a meningitis outbreak to a competing antibiotic that was known to be effective at a higher dose than that used during the trial. Goldacre writes that 11 children died, divided almost equally between the two groups. He also writes that the participants were not told that the competing antibiotic at the effective dose was available in the next-door building from Médecins Sans Frontières.

"Bad Regulators"

Chapter three describes the concept of "regulatory capture," whereby a regulator – such as the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK, or the Food and Drug Administration (FDA) in the United States – ends up advancing the interests of the drug companies rather than the interests of the public. Goldacres writes that this happens for a number of reasons, including the revolving door of employees between the regulator and the companies, and the fact that friendships develop between regulator and company employees simply because they have knowledge and interests in common. The chapter also discusses surrogate outcomes and accelerated approval, and the difficulty of having ineffective drugs removed from the market once they have been approved. He argues that regulators do not require that new drugs offer an improvement over what is already available, or even that they be particularly effective.

"Bad Trials"

"Bad Trials" examines the ways in which clinical trials can be flawed. He writes that this happens by design and by analysis, and that it has the effect of maximizing a drug's benefits and minimizing harm. There have been instances of fraud, though he says these are rare. More common are what he calls the "wily tricks, close calls, and elegant mischief at the margins of acceptability."

These include testing drugs on unrepresentative, "freakishly ideal" patients; comparing new drugs to something known to be ineffective, or effective at a different dose or if used differently; conducting trials that are too short or too small; and stopping trials early or late. It also includes measuring uninformative outcomes; packaging the data so that it is misleading; ignoring patients who drop out (using per-protocol analysis rather than intention to treat analysis); changing the main outcome of the trial once it has finished; producing subgroup analyses that show apparently positive outcomes for certain tightly defined groups (such as Chinese men between the ages of 56 and 71), in order to hide an overall negative outcome; and conducting "seeding trials," where the objective is to persuade physicians to use the drug.

Another criticism is that outcomes are presented in terms of relative risk reduction to exaggerate the apparent benefits of the treatment. For example, he writes, if four people out of 1,000 will have a heart attack within the year, but on statins only two will, that is a 50 percent reduction if expressed as relative risk reduction. But if expressed as absolute risk reduction, it is a reduction of just 0.2 percent.

"Bigger, Simpler Trials"

In chapter five Goldacre suggests using the General Practice Research Database in the UK, which contains the anonymized records of several million patients, to conduct randomized trials to determine the most effective of competing treatments. For example, to compare two statins, atorvastatin and simvastatin, doctors would randomly assign their patients to one or the other. The patients would be followed up by having data about their cholesterol levels, heart attacks, strokes and deaths taken from their computerized medical records. The trials would not be blind – patients would know which statin they had been prescribed – but Goldacre writes that it's unlikely they would have such firm beliefs about which one is preferable to the extent that it could affect their health.

"Marketing"

In the final chapter, Goldacre looks at how doctors are persuaded to prescribe "me-too drugs," brand-name drugs that are no more effective than significantly cheaper off-patent ones. He cites as examples the statins atorvastatin (Lipitor, made by Pfizer) and simvastatin (Zocor), which he writes seem to be equally effective, or at least there is no evidence to suggest otherwise. Simvastatin came off patent several years ago, yet there are still three million prescriptions a year in the UK for atorvastatin, costing the National Health Service (NHS) an annual ₤165 million extra.

He addresses the issue of medicalization of certain conditions (or, as he argues, of personhood), whereby pharmaceutical companies "widen the boundaries of diagnosis" before offering solutions. Female sexual dysfunction was highlighted in 1999 by a study in the Journal of the American Medical Association, which alleged that 43 percent of women were suffering from it. Goldacre writes that, after criticism appeared in The New York Times, two of the three authors declared that they had undertaken consultancy work for Pfizer, which at the time was preparing to launch female Viagra (UK-414,495).

The chapter examines celebrity endorsement of certain drugs, the extent to which claims in advertisements aimed at doctors are appropriately sourced, and whether direct-to-consumer advertising (currently permitted in the US and New Zealand) ought to be allowed. It also discusses how PR firms handle and promote patients who complain in the media about a certain drug not being made available by the funder, which in the UK is the NHS, advised by the National Institute for Health and Clinical Excellence (NICE). Two breast-cancer patients who were campaigning in the UK in 2006 for Herceptin, made by Roche, to be available on the NHS were being handled by a law firm working for Roche. The historian Lisa Jardine, who was suffering from breast cancer, told The Guardian she had also been approached by a PR firm working for the company.

The chapter also covers the influence of drug reps, how ghostwriters are employed by the drug companies to write papers for academics to publish, how independent the academic journals really are, how the drug companies finance doctors' continuing education, and how patients' groups are often funded by industry.

Afterword: "Better Data"

In the afterword and throughout the book, Goldacre makes suggestions for action by doctors, medical students, patients, patient groups and the industry. He advises doctors, nurses and managers to stop seeing drug reps, to ban them from clinics, hospitals and medical schools, to declare online and in waiting rooms all gifts and hospitality received from the industry, and to remove all drug company promotional material from offices and waiting rooms. (He praises the website of the American Medical Student Association – www.amsascorecard.org – which ranks institutions according to their COI policies, writing that it makes him "feel weepy.") He also suggests that regulations be introduced to prevent pharmacists from sharing doctors' prescribing records with drug reps.

He asks academics to lobby their universities and academic societies to forbid academics from being involved in ghostwriting, and to lobby for "film credit" contributions at the end of every academic paper, listing everyone involved, including who initiated the idea of publishing the paper. He also asks for full disclosure of all past clinical trial results, and a list of academic papers that were, as he puts it, "rigged" by industry, so that they can be retracted or annotated. He asks drug company employees to become whistleblowers, either by writing an anonymous blog, or by contacting him.

He advises patients to ask their doctors whether they accept drug-company hospitality or sponsorship, and if so to post details in their waiting rooms, and to make clear whether it is acceptable to the patient for the doctor to discuss his or her medical history with drug reps. Patients who are invited to take part in a trial are advised to ask, among other things, for a written guarantee that the trial has been publicly registered, and that the main outcome of the trial will be published within a year of its completion. He advises patient groups to write to drug companies with the following: "We are living with this disease; is there anything at all that you're withholding? If so, tell us today."

Reception

The Economist described the book as "slightly technical, eminently readable, consistently shocking, occasionally hectoring and unapologetically polemical. ... This is a book that deserves to be widely read, because anyone who does read it cannot help feeling both uncomfortable and angry." Helen Lewis in the New Statesman called Bad Pharma an important book, "engaging, polemic and elegant." The Association of the British Pharmaceutical Industry (APBI) replied in the New Statesman that Goldacre is "stuck in a bygone era where pharmaceutical companies wine and dine doctors in exchange for signing on the dotted line." Luisa Dillner, writing in The Guardian, called the book a "thorough piece of investigative medical journalism," which she wrote is brought to life by Goldacre's passion, accessible writing, and careful gathering of evidence.

Andrew Jack in the Financial Times called it "an intense and a depressing read – both for the facts outlined but also the limited nuance." He wrote that "Goldacre is at his best in methodically dissecting poor clinical trials. He rightly stresses the im­portance of transparency so that third parties can pore over the data independently. ... He is less strong in ex­plaining the complex background reality, such as the general constraints and individual slips of regulators and pharma companies' employees. Nor is he able to assess the net impact of the current system: how many lives have been improved compared with those hurt by the current, if imperfect system, which has led to extraordinary new treatments in recent years for HIV, rheumatoid arthritis and cancer."

Max Pemberton wrote in The Daily Telegraph that "this is a book to make you enraged – properly, bone-shakingly furious – because it's about how big business puts profits over patient welfare, allows people to die because they don't want to disclose damning research evidence, and the tricks they play to make sure doctors do not have all the evidence when it comes to appraising whether a drug really works or not."

The APBI issued a press release in response to the book, writing that the pharmaceutical industry is responsible for the discovery of 90 percent of all medicines, and that it takes an average of 10 to 12 years, and £1.1bn, to introduce a medicine to the market, with just one in 5,000 new compounds receiving regulatory approval. This makes research and development an expensive and risky business. They write that the industry is one of the most heavily regulated in the world, and that they are committed to ensuring full transparency in the research and development of new medicines. They also argue that the examples Goldacre offers are "long documented and historical, and the companies concerned have long addressed these issues." Goldacre writes in the book that "the most dangerous tactic of all is the industry's enduring claim that these problems are all in the past."

Publication details

• Bad Pharma: How drug companies mislead doctors and harm patients. Fourth Estate, 2012 (UK). ISBN 978-0-00-735074-2

• Faber and Faber, 2013 (US). ISBN 978-0-86547-800-8
• Signal, 2013 (Canada). ISBN 978-0-7710-3629-3

See also

Books

• Big Pharma (2006) by Jacky Law
• Side Effects (2008) by Alison Bass
• Anatomy of an Epidemic (2010) by Robert Whitaker

Lists

• List of books about the politics of science
• List of drugs
• List of pharmaceutical companies
• List of pharmaceutical manufacturers in the UK
• List of largest pharmaceutical settlements
• List of off-label promotion pharmaceutical settlements

Miscellaneous

• Aggregate Spend
• Cochrane Collaboration
• Ethics in pharmaceutical sales
• Meta-analysis
• History of pharmacy
• International Pharmaceutical Federation
• Pharmaceutical fraud
• Pharmaceutical industry in the UK
• Pharmaceutical marketing
• Systematic review

Miscellaneous (contd.)

• GlaxoSmithKline#Controversies
• Paroxetine#Controversy
• Reboxetine
• Rosiglitazone
• TGN1412
• Tamiflu

Further reading

External links

• Bad Pharma, publisher's website.
• badscience.net, Ben Goldacre's website.
• "Bad Science", Goldacre's column for The Guardian.
• "Why doctors don't know what they're prescribing", extract from Bad Pharma.
• Chalmers, Iain. Testing Treatments interactive.

Articles

• Brice, Makini. "Pharmaceutical Companies Cherry Pick Data for Drug Approval, Sweep Bad Results Under the Rug", Medical Daily, 28 September 2012.
• Burke, Maria. "GSK pledge on trials transparency", Chemistry World, 17 October 2012.
• Carlat, Daniel. "Dr. Drug Rep", New York Times magazine, 25 November 2007.
• Goldacre, Ben. "Is the conflict of interest unacceptable when drug companies conduct trials on their own drugs? Yes", British Medical Journal, 29 November 2009.
• Goldacre, Ben. "Drug companies must publish all trial results", The Times, 23 October 2012.

• "Calls to end ‘national scandal’ of stifled clinical trial results", The Times health editor, 23 October 2012.

• Haynes, Laura; Service, Owain; Goldacre, Ben; Torgerson, David. "Test, Learn, Adapt: Developing Public Policy with Randomised Controlled Trials", Cabinet Office Behavioural Insights Team (UK), June 2012.
• Hennessy, Mark. "Putting the drug companies' research to the test", The Irish Times, 29 September 2102.
• McClenaghan, Maeve. "Why Big Pharma is bad for your health", Bureau of Investigative Journalism, 28 September 2012.
• Metro. "Ben Goldacre: Too many people die due to distortions in medical science" (interview), 3 October 2012.
• Rehman, Jalees. "Can the Source of Funding for Medical Research Affect the Results?", Scientific American, 23 September 2012.
• Rutherford, Adam. "Podcast Extra: Ben Goldacre", Nature, 28 September 2012.
• Szalavitz, Maia. "A Doctor’s Dilemma: When Crucial New-Drug Data Is Hidden", Time magazine, 24 September 2012.
• Tucker, Ian. "Ben Goldacre: 'It's appalling ... like phone hacking or MPs' expenses'", The Observer, 7 October 2012.

Books

• Angell, Marcia. The Truth about Drug Companies: How They Deceive Us and What to Do About It. Random House, 2004.
• Carlat, Daniel. Unhinged: The Trouble with Psychiatry - A Doctor's Revelations about a Profession in Crisis. Free Press, 2010.
• Elliott, Carl. White Coat Black Hat: Adventures on the Dark Side of Medicine. Beacon Press, 2010.
• Evans, Imogen; Thornton, Hazel; Chalmers, Iain; and Glasziou, Paul. Testing Treatments. Pinter & Martin, 2011, first published 2006 (see www.testingtreatments.org).
• Greenhalgh, Trisha. How to Read a Paper: The Basics of Evidence-Based Medicine. BMJ Books, 2010.
• Light, Donald W. (ed.). The Risks of Prescription Drugs. Columbia University Press, 2010.
• Nesi, Tom. Poison Pills: The Untold Story of the Vioxx Drug Scandal. Thomas Dunne Books, 2008.
• Smith, Richard. The Trouble with Medical Journals. CRC Press, 2006.
• Peterson, Melody. Our Daily Meds. Farrar, Straus and Giroux, 2008.

Radio

• BBC Radio 4. "Pharmaceutical regulators have been 'unethical'", Today programme, 25 September 2012 (radio interview with Ben Goldacre and Stephen Whitehead of the Association of the British Pharmaceutical Industry).
• Kim Hill. Ben Goldacre's Bad Pharma", Radio New Zealand National, 27 October 2012 (radio interview with Goldacre; automatic download).