Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients (50 page)

I also strongly encourage you to become a whistleblower, whenever you see things being done that are wrong, using three main vehicles, in ascending order of melodrama. At the simplest level, if you can handle the secrecy properly, write an anonymous blog, explaining what you see on a daily basis: the banal, mild distortions, the days when you’re asked to hunt in a data file and cherry-pick any pattern that makes your company’s drug look good, the unofficial sales advice you’re given as a drug rep, and so on. Next, I’d appreciate specific leaks, on [email protected] (but please don’t send me confidential information from your work email address). Lastly, many of you reading this have access to large quantities of data or documents that would change the lives of patients, and help to prevent ongoing suffering and harm. I would appreciate a data dump, on the scale of the US Iraq and Afghanistan war records, and if I’m honest, I’m surprised and disappointed this hasn’t happened yet. If you need any help, just ask: I will do everything I can to assist you.

Professional bodies

The Royal Colleges, the faculties, and the societies, have failed us. There is still no professional body in the UK, other than the tiny Faculty of Pharmaceutical Medicine, that has stood up and declared that withholding trial data is unethical, immoral and grounds for expulsion of its members. If these organisations have integrity, they will fix this; alternatively, if the senior members truly think that withholding trial data is fine and acceptable, then they should come out and say so, clearly, to their members and to patients. I’m not the first to raise this, so I have low expectations. If you are a member of one of these organisations, you could write and ask why it does not have a policy of chastising and expelling people who harm patients by withholding trial data. Please, send me their responses, or better still, simply post them online.

Funders

Money is short, outside of industry-funded research. Organisations like the National Institute for Health Research already do a great job, funding trials on important questions that drug companies won’t want to pay for: it assesses the benefits of older drugs, for example, or of treatments that don’t involve commercial products (I should say that I sit on one of these funding committees). But I believe that public funders should have two further priorities. Firstly, there are some small outstanding evidence gaps in our knowledge of how industry distorts medical prescribing practice, and this is not a field that the pharmaceutical industry is likely to fund. More than that, as I argued at the beginning of the marketing section: the great horizon for evidence-based medicine is finding new methods and tools for disseminating the evidence we already have, to doctors and other decision-makers. This will require innovative collaboration between coders, pharmacists, librarians, doctors and academics. At the simplest level, I’m always frustrated that I can’t press a button, when reading a systematic review, to say ‘notify me when this summary is updated with new trial results’. In more elaborate terms, it’s clear that we should be moving medical knowledge and trial results into structured databases; and perhaps embedding high-quality contextual advice into a doctor’s routine workflow, as they sit at the computer in their office.

Academics and nerds

This book is filled with exciting untapped areas. There are the big jobs, on organising medical knowledge, from the section above, but also an avalanche of smaller studies, many of which could be done as undergraduate dissertations. Do a fact-checking audit of claims from drug reps; gather quantitative evidence on industry sponsorship in your medical school; find out about your university’s policies on hiding trial data (or anything else); and then collaborate with other medical schools, to gather comparative national data. Share your ideas, and publish your results: we are all cheering you on.

GLOSSARY

ABPI – The Association of the British Pharmaceutical Industry.

ACCME – The Accreditation Council for Continuing Medical Education.

BNF
–
British National Formulary
.

CME – Continuing medical education.

CSR – Clinical study report.

EMA – The European Medicines Agency, the European drugs regulator.

FDA – The Food and Drug Administration, the US drugs regulator.

GCP – Good Clinical Practice guidelines.

Generic drug – When a drug is first invented, it is owned by the company, and no one else is allowed to manufacture and sell it. A drug usually comes off patent eighteen years after it was first registered, and about ten years after it comes onto the market. After that, any company can make a copy of it, as with very old drugs such as paracetamol or aspirin. When this happens, you can’t make much profit out of selling it.

GMC – General Medical Council.

ICH – International Conference on Harmonisation.

ICMJE – International Committee of Medical Journal Editors.

JAMA
–
Journal of the American Medical Association
.

KOL – ‘Key opinion leader’.

MHRA – Medicines and Healthcare products Regulatory Agency.

NEJM
–
New England Journal of Medicine
.

Off-label – A drug is allowed onto the market by a regulator on the condition that it can only be marketed for use in a specific medical condition. Doctors can use the drug for other medical problems if they wish, but this use is ‘off-label’.

Off patent – A drug that is out of patent (see generic drug).

PMCPA – Prescriptions Medicines Code of Practice Authority.

Publication bias – The phenomenon whereby trials with results regarded as unflattering or uninteresting are left unpublished.

SSRI – Selective serotonin reuptake inhibitor.

Surrogate outcome – Real-world problems are what we really want to change with medicines: things like death, heart attack or stroke. A surrogate outcome is something that is easier to measure, like blood pressure or cholesterol levels, that we hope is a proxy for those outcomes. Often they are not as good at predicting real-world outcomes as we think.

ACKNOWLEDGEMENTS, FURTHER READING AND A NOTE ON ERRORS

I have been taught, corrected, calibrated, cajoled, entertained, encouraged and informed by a very large number of people, including John King, Liz Parratt, Steve Rolles, Mark Pilkington, Shalinee Singh, Alex Lomas, Liam Smeeth, Josie Long, Ian Roberts, Tim Minchin, Ian Sample, Carl Heneghan, Richard Lehman, Dara Ó Briain, Paul Glasziou, Hilda Bastian, Simon Wessely, Cicely Marston, Archie Cochrane, William Lee, Brian Cox, Sreeram Ramagopalan, Hind Khalifeh, Martin McKee, Cory Doctorow, Evan Harris, Muir Gray, Amanda Burls, Rob Manuel, Tobias Sargent, Anna Powell-Smith, Tjeerd van Staa, Robin Ince, Roddy Mansfield, Rami Tzabar, Phil Baker, George Davey-Smith, David Pescovitz, Charlotte Wattebot-O’Brien, Patrick Matthews, Giles Wakely, Claire Gerada, Andy Lewis, Suzie Whitwell, Harry Metcalfe, Gimpy, David Colquhoun, Louise Burton, Simon Singh, Vaughan Bell, Richard Peto, Louise Crow, Julian Peto, Nick Mailer, Rob Aldridge, Milly Marston, Tom Steinberg, Mike Jay, Amber Marks, Reg, Mum, Dad, Josh, Raph, Allie, and Lou. I’m hugely indebted to the late Pat Kavanagh, Rosemary Scoular, Lara Hughes-Young, and especially Sarah Ballard, who is amazing. Robert Lacey has copy-edited my last two books, he is gentle. Louise Haines has been mighty.

There are tools that made this book better, especially Zotero, Scrivener, Evernote, ReaditLater, IntervalTimer and Repligo. AntiSocial is a piece of software that irreversibly disables Twitter and Gmail on your computer when you’re working: I highly recommend it. In recent years I’ve had day jobs supported by the National Institute for Health Research, the Scott Trust, the Wellcome Trust, Nuffield College, Oxford, and the NHS, and a bursary from the Oxford University Business Economics Programme.

It’s a common joke in evidence-based medicine that whenever you think you’ve had an idea, Iain Chalmers has probably written it up in an essay fifteen years earlier. He helped to formulate many of the key ideas in evidence-based medicine, and to spot the problems, and I hope I’ve attributed enough to him. There are also many other academics whose work comes up repeatedly: some of them I’ve met, most of them I’ve not, but where you see recurring names in the references, it’s fair to say that we all stand on their shoulders. There are huge rewards in medicine, but they’re not reliably in the right places. Many of the people whose work is cited in this book have taken a personal hit, on income and eminence, to work on the serious systemic problems in medicine. They are quiet heroes. It’s an honour to spread their work more widely.

There are many excellent review papers on the issues raised in this book, and I have highlighted them in the references wherever possible. I have specifically tried to seek out papers that are freely accessible (look for the references to a journal called
PLoS
, in particular), though some sadly are still behind academic journal paywalls.

There are also many excellent books that have covered some of the issues around bad behaviour by the pharmaceutical industry, though all are US-focused, many are now almost a decade old, and none have focused missing data. If you are keen to read more on any specific area, there are several books that have influenced my thinking over the years.

Jerome Kassirer was editor of the
NEJM
, and his
On the Take
(2004) is great on the marketing issues, and the way that continuing medical education in the US has been captured by industry. Marcia Angell was also
NEJM
editor, and her book
The Truth About Drug Companies
(2005) first brought the story of marketing, institutional corruption and bad evidence to a larger audience. Richard Smith is the previous editor of the
BMJ
, and his book
The Trouble With Medical Journals
(2006) explains itself. Ray Moynihan’s various books on medicalisation are all excellent. Donald Light recently edited
The Risks of Prescription Drugs
(2010), which is a good collection on contemporary problems, especially the lack of innovation. Melody Petersen, previously of the
New York Times
, wrote
Our Daily Meds
(2008), which is excellent on marketing in the US. Daniel Carlat is a bioethicist, and his
White Coat Black Hat
(2007) is great on the ethical issues around drug testing. Tom Nesi’s book on Vioxx is magnificent.

While criticising bad behaviour from industry is important, I’m also struck that the public have little opportunity to read about the basic techniques used to appraise new treatments, find out what works, and spot what harms.
Testing Treatments
(2006, second edition 2011) by Imogen Evans, Hazel Thornton, Iain Chalmers and Paul Glasziou remains the single go-to book on this topic in my view, published in several languages and also available free online at testingtreatments.org (I should mention that I wrote the foreword).
Powerful Medicines
(2005) by Jerry Avorn is the first attempt I’ve seen by a pharmacoepidemiologist to explain the science of side effects monitoring to the public.
How to Read a Paper
by Trisha Greenhalgh remains the medical-student bible on critically appraising academic papers, and it can be understood by anyone.

Finally, I have no doubt that there will be some mistakes in this book, whether they are small slips, misinterpretations or perhaps unfair slurs. I should say that I’ve written it to illustrate underlying themes, not to rubbish any particular drug or company; and so I hope the criticism has been roughly evenly distributed, perhaps according to market share. I certainly don’t think any one company is any better than any other. If you do find an error of fact, do let me know, and if it’s a genuine error, I will happily correct the text. In the unlikely event that any example I’ve used is simply wrong, there will be another to slot in its place. If you like – if it’s in your nature, and if that is how you’d like others to see you – you can point out mistakes with self-righteous fury. Or you can just point them out. I’ll be cheerful in either case, but more than anything: I’m certain there is no error that will change the argument of the book, so your feedback will help to make the argument stronger.

On a related note, in the UK (especially) there is a vogue for large companies to sue writers over critical concerns they have raised, in the public interest, on matters of science and health. I’ve experienced success in libel cases, and have helped to drive a partially successful campaign to change the libel laws in Britain. Even where libel cases have been technically successful – though for clarity, none against me has ever been – these have often backfired on the litigant’s reputation. There is a strong sense among the public that libel is used to dissuade people from raising legitimate concerns, or to create anxiety, encouraging writers to police themselves and steer away from anything critical. I mention this because, as I said, I’ve tried very hard to be accurate in this book.

If you genuinely feel that you or your company has been libelled, or that something in here is plainly untrue, I encourage you to drop me a note, so we can look at your concerns and change what’s written, if appropriate, or clarify. I offer this freely, with no sense of either fear or threat: I just think it’s how things should work. As I have repeatedly reiterated throughout this book, the problems it describes are systemic and widespread. The specific stories I have included are intended to illustrate points of methodology, and those points would only make sense if they were attached to real studies. I hope you’ll view any story that relates to you in the spirit in which it is intended, and recognise the genuine concern and public interest in the issues raised, as well as the room for improvement in your industry.