As many readers will know (do I have many readers?) most of my working life has been spent with Big Pharma. I make no apology for that. It suits me, as it’s science based, with a mission to benefit humanity – at a profit. So imagine my grief that a book such as Ben Goldacre’s latest should be necessary. I haven’t read Bad Pharma yet, but knowing Ben as I do, I have no doubt that there’s more than a kernel of truth to it. Indeed I know that to be the case.
In my early years on the commercial side, of course I was trained to present clinical evidence in the best possible light. Does anyone remember the recession of 1975 or thereabouts? A certain marketing department invented the disease ‘economic malaise’ for which a certain tricyclic antidepressant was highly effective (allegedly). At another company, we had a non-steroidal anti-inflammatory in a crowded market. It was known within the company as ‘a salesman’s product’ as it was tacitly admitted to be no better than the competition. Indeed the sales force was trained to minimise its shortcomings. However some of the reps were not so easily convinced by the weak clinical studies with which they were armed. The company did invest in more ‘research’, but for this product only in uncontrolled studies designed to ‘seed’ the product among GPs.
Another time, I was told that I needed a ‘passion for the product’. This is something that needs to be understood. No enterprise can really succeed without people to champion what it is doing. In this sense, marketers are no different from scientists. We all have our enthusiasms, we all need something to get us out of bed in the morning. Hence, we are all susceptible to biasses born of emotion. It’s important to accept this, and to consider how to handle it for the common good.
Well that was decades ago, and nothing like that happens now. Or does it? The difference is that Big Pharma is rather more subtle these days. But not so subtle that companies don’t sometimes get caught out, and I have recently addressed elsewhere the cases of Roche and Glaxo SmithKline. In my 25-year life of consulting for Big Pharma, I have more than once had to tell clients that what they were doing was against my professional advice regarding regulatory and/or ethical compliance. A commonly contentious issue is interpretation of data. I remember having a considerable battle over a safety study, from which the company was determined to derive an efficacy message – when efficacy was not even in the protocol objectives. Many years ago, I worked in a medical department which operated largely as a branch of sales and marketing. I did me no good to point out the constraints of the industry code of practice.
But I do hope that Ben’s book doesn’t lead the reader to believe that all of Pharma is Bad. I’m told that there is substantial discussion of safety data reporting. To quote from chapter 1:
You only have to tell the regulator about side effects reported in studies looking at the specific uses for which the drug has a marketing authorisation.
He also says that there is no need to tell the regulators about safety data from trials that take place outside the EU.
From this, it looks as if there are huge regulatory gaps in reporting adverse events. There may be gaps, but they are not for want of trying to close them. For the uninitiated, let me outline some of the legal requirements for clinical trials.
An adverse event in a clinical trial is defined as any unwanted change in the patient’s condition, and must be reported. Note that the question of causality is immaterial to the question of whether the event should be reported. If a meteorite fell out of the sky and squashed the patient flat, that would be an event (certainly adverse) that would have to be reported.
In addition, this tragic event with the celestial body would also qualify as a SERIOUS adverse event (SAE). Such events include what some of you might consider fairly humdrum, such as any unscheduled hospital stay. SAEs are subject to expedited reporting, which means they must be reported to the sponsor and the regulatory authority within very strict time limits, not just at the end of the trial. Overall, every adverse event, serious and non-serious, must be reported to the regulatory authority in the final report.
There is a further category of adverse event, called in the EU a SUSAR. This is a serious unexpected suspected adverse reaction. Note that now we are considering causality, and there are clearly defined criteria for that, set out in the trial protocol. But even if the event doesn’t qualify under those criteria, the doctor doing the trial can decide that the study drug might have caused the event, independently of the sponsor. Now all SUSARs are not only subject to expedited reporting to the regulators, as are all SAEs, but they have to be reported to all the other investigators in the trial, wherever they are in the world. Those investigators have to sign to say they have received and read the reports, and they then have to send them to the ethics committees which approved the trial at their institution.
I have described here only a very small part of the process for safety data monitoring in clinical trials. Vast armies of people labour away in drug companies, poring over streams of SAE reports, checking that they are complete (they rarely are), and repeatedly chasing the investigators for corrections. It is such a huge and complex operation that I am surprised it works as well as it does. Sadly, sometimes it goes badly wrong. There are no excuses, it has to get better, as Goldacre has quite rightly pointed out. But I and several colleagues are at a loss as to how he has derived the statements above.
So I hope you can understand my dismay at the manner in which the UK industry has responded. When I joined my first pharmaceutical company in 1974, I pretty quickly realised that the ABPI was a largely toothless watchdog. It hasn’t improved noticeably in almost four decades. I’ll leave you to read their response, but suffice it for me to say that dismissing Goldacre’s arguments in a few words, and then writing several paragraphs on how wonderful the industry is, doesn’t actually address the points at issue.
There are many people who would like us to believe that prescription drugs do more harm than good. The evidence gives the lie to that. There are many studies which clearly show that, if you can get patients to take their medicines, you save money. A good deal of the evidence comes from the USA, where the health insurers and managed care companies (for all their many faults) have an avid interest in reducing costs. For example, the Asheville Project showed that if you get patients to comply with their prescribed treatment, you reduce overall health care costs - and where drugs cost twice as much as they do in the UK. This would not be happening if the drugs didn’t work.
So knowing what I do about Big Pharma, and from the inside, I am sure that Bad Pharma is a worthwhile and necessary book. The industry is not quite as bad as Goldacre says, but it’s nowhere near as good as the ABPI seems to think. I won’t enjoy reading it, but I feel I have to.