Medical miracles vs the MHRA

Chlorodyne_advertI’m looking at an advertisement for a medicine called Chlorodyne. The most wonderful and reliable remedy ever discovered cures coughs, consumption, bronchitis and asthma. It’s effective against diphtheria, fever, croup and ague. It acts like a charm on diarrhoea, cholera and dysentery.  It cuts short attacks of epilepsy, hysteria, palpitations and spasms. And it takes away the pain of neuralgia, rheumatism, gout, cancer, toothache and meningitis.

Wow, that sounds like a handy one to have in the bathroom cabinet. But the advertisement is old and the drug would never get past today’s Medicines and Healthcare Regulatory Authority (MHRA), the UK body that judges whether medicinal products work and are safe. Chlorodyne numbed pain rather effectively, since it contained opium, cannabis and chloroform; unfortunately it was also highly addictive and dangerous.

How did we get from the outrageous claims and casual use of potent substances to a situation where it can take 15 years and hundreds of millions of pounds to get your product onto the shelf? Regulation of medicines developed in a piecemeal way at the beginning of the 20th century, but really got underway with the aftershocks of thalidomide. Manufacturer Grünenthal conducted only perfunctory testing and suppressed reports that it was causing birth defects; the UK, along with much of Europe and the US, responded to the disaster by dramatically strengthening drug regulation.

Regulations now cover every aspect of drug development, from initial toxicity testing in animals to the wording of the patient leaflet. The administrative and scientific challenge of working a promising substance from the lab to clinical trials is huge; at each stage the research must meet the standards of the regulator.

Has legislation gone too far, piling intolerable expenses on pharma and stifling innovation in the industry? Technological change is happening all around us at a tremendous rate – consider how your mobile phone has changed over the past decade – yet a drug first dreamt up in 2003 may still be moving slowly through the development cycle. In an era where we can model the required protein on a computer and synthesise it, how can medical practice keep up with the promise?

Lord Saatchi’s Medical Innovation Bill is motivated by his frustration that approval processes take so long. It would allow doctors to use unlicensed treatments on cancer patients without fear of prosecution, with certain safeguards. The bill has been widely criticised – even by some of the patient groups most eager to obtain urgent treatment – as undermining the proper collection of evidence by gold-standard double-blind clinical trials, and opening the door to quacks.

Yet anyone who says there is no case to answer is overlooking a highly relevant recent example: patients treated for Ebola in the West have been given ZMapp or other unlicensed treatments. Few seem to think it unreasonable for the very sick individuals to make that decision (one argument against offering untested treatments is that desperate terminally ill people are incapable of truly informed consent). And faced with a public health crisis this serious, most people accept that both vaccines and treatments may need to be fast-tracked.

Similar issues arose the last time the human race faced a pandemic. In the film Dallas Buyers Club, an AIDS patient dissatisfied with AZT – then the only treatment on offer, and a highly toxic drug with nasty side-effects – smuggles unlicensed drugs across the border from Mexico. Eventually he is selling them to hundreds of patients. The US Food and Drug Administration (FDA) is the bad guy:

Richard Barkley [FDA official]: Mr Woodroof, I’m afraid that you’re nothing more than a common drug dealer, so if you’ll excuse us…

Ron Woodroof: Oh, I’m the drug dealer? No, you’re the fuckin’ drug dealer. I mean, goddamn, people are dyin’. And y’all are up there afraid that we’re gonna find an alternative without you.

The film is somewhere between an interpretation and a misrepresentation: debate still rages about the history of AZT, but most of what the real-life Woodroof brought in proved useless, while AZT is still used as part of the successful treatment regime to control HIV.

Since April 2014 there has been a limited early access programme in the UK. New treatments for life-threatening and highly debilitating conditions can be given the ‘promising innovative medicine’ (PIM) designation. A PIM can then be given an official scientific opinion on the risks and benefits, which will be published on the MHRA website for doctors to consider. Doctors can already prescribe unlicensed treatments but hesitate for fear of litigation and lack of information, so the scheme could bring important innovations to patients a few years earlier. Two treatments – one a therapy for cancer – have been designated as PIMs to date.

In the end, our obsession with getting hold of the fruits of medical research may be based on a fallacy. Lord Saatchi’s Bill assumes there are drugs held up in development that will cure late-stage cancer; there may be one or two in the pipeline, but there will also be some downright duds, as well as some that extend life only marginally. What are the chances of an individual getting the right drug at the right time in the right dose, without benefit of all the information that comes from a controlled clinical trial?

We all love a scientific miracle, but medicine mostly advances in small increments – a slightly more effective blood-pressure drug, a statin with fewer side-effects, radiotherapy more precisely targeted on the tumour. Where we’ve got to through all these innovations is stunning, but most of the steps on the way here were pretty mundane.