Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients is a book by the 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.Luisa Dillner, "Bad Pharma by Ben Goldacre – review", The Guardian, 17 October 2012. It was published in the UK in September 2012 by the Fourth Estate imprint of HarperCollins, and 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 own products and much of doctors' continuing education, that clinical trials are often conducted on small groups of unrepresentative subjects and negative data is routinely withheld, and that apparently independent academic papers may be planned and even ghostwritten by pharmaceutical companies or their contractors, without disclosure.Bad Pharma, x–xi, 287ff; "Pick your pill out of a hat", The Economist, 29 September 2012. Describing the situation as a "murderous disaster", he makes suggestions for action by patients' groups, physicians, academics and the industry itself.Bad Pharma, xii, 357ff.
Responding to the book's publication, the Association of the British Pharmaceutical Industry issued a statement in 2012 arguing that the examples the book offers were historical, that the concerns had been addressed, that the industry is among the most regulated in the world, and that it discloses all data in accordance with international standards."ABPI statement on Ben Goldacre's book 'Bad Pharma'" , Association of the British Pharmaceutical Industry, 5 October 2012.Ben Adams, "Goldacre takes ABPI to task over book snub" , Pharma Times, 12 October 2012.
In January 2013 Goldacre joined the Cochrane Collaboration, British Medical Journal and others in setting up AllTrials, a campaign calling for the results of all past and current clinical trials to be reported."About", alltrials.net; Tracey Brown, "It's time for AllTrials registered and reported" , The Cochrane Library, 30 April 2013. The British House of Commons Public Accounts Committee expressed concern in January 2014 that drug companies were still only publishing around 50 percent of clinical-trial results.David Tovey, "Why the Public Accounts Committee Report on Tamiflu Is Important for Us All", HuffPost, 3 January 2014.Rajeev Syal, "Drug companies accused of holding back complete information on clinical trials", The Guardian, 3 January 2014.
Synopsis Introduction Goldacre writes in the introduction of Bad Pharma that he aims to defend the following:
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.Bad Pharma, xi (paragraph break added for ease of reading).
Chapter 1: "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 a 2007 journal article published in PLOS Medicine, researchers studied every published trial on statins, drugs prescribed to reduce cholesterol levels. In the 192 trials they looked at, industry-funded trials were 20 times more likely to produce results that favoured the drug.Bad Pharma, 2; for the study,
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 patients are selected to make a positive result more likely. In addition, the data are analysed as the trial progresses. 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 argues, doctors may have no idea what the effects are of the drugs they prescribe.Bad Pharma, 4–7, 12.
An example he gives of the difficulty of obtaining missing data from drug companies is that of oseltamivir (Tamiflu), manufactured by Roche to reduce the complications of bird flu. Governments spent billions of pounds stockpiling this, based in large part on a meta-analysis that was funded by the industry. Bad Pharma charts the efforts of independent researchers, particularly Tom Jefferson of the Cochrane Collaboration Respiratory Group, to gain access to information about the drug.Bad Pharma, 81ff; Tom Jefferson, et al., "A review of unpublished regulatory information from trials of neuraminidase inhibitors (Tamiflu - oseltamivir and Relenza - zanamivir) for influenza", Cochrane Summaries, 17 October 2012.
Chapter 2: "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.Bad Pharma, 104–110. Participants are usually taken from the poorest groups in society, and outsourcing increasingly means that trials may be conducted in countries with low wages by contract research organizations (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.Bad Pharma, 113–114.
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 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 people of Asian descent metabolize drugs differently from Westerners.Bad Pharma, 115.
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 was used during the trial. Goldacre writes that 11 children died, divided almost equally between the two groups. The families taking part in the trial were apparently not told that the competing antibiotic at the effective dose was available from Médecins Sans Frontières in the next-door building.Bad Pharma, 117.
Chapter 3: "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. Goldacre 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.Bad Pharma, 123ff. 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 Pharma, 143ff.
Chapter 4: "Bad Trials" "Bad Trials" examines the ways in which clinical trials can be flawed. Goldacre 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."Bad Pharma, 171.
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.Bad Pharma, 176, 180–187, 191–193. It also includes measuring uninformative outcomes; packaging the data so that it is misleading; ignoring patients who drop out (i.e. using per-protocol analysis, where only patients who complete the trial are counted in the final results, rather than intention-to-treat analysis, where everyone who starts the trial is counted); 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), thereby hiding an overall negative outcome; and conducting "seeding trials," where the objective is to persuade physicians to use the drug.Bad Pharma, 194–198, 200–212.
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.Bad Pharma, 216–217.
Chapter 5: "Bigger, Simpler Trials"