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.

DWP EmployAbility Campaign

Here’s a difficult brief: from your home in London, find disabled people who are working in small- and medium-sized enterprises in Yorkshire, then meet them and their employers and write up their stories.

That’s what I was tasked with during six months on a campaign run by Department for Work and Pensions. Called EmployAbility, it encouraged businesses to take on disabled people. It wasn’t easy: many disabled people work, but it’s more usual for them to find jobs in government, a charity or a large corporation. Some people were happy to chat informally but understandably didn’t want their interview and photograph used in publicity.

When I did find people who met the criteria and were willing to take part, their stories were inspiring: many had struggled not just with long-term illness or disability, but with the frustration of unemployment and dependence on benefits. Now they were in work, and whether they were a part-time cleaner or a well-paid professional, it meant a lot to get out of the house, meet people, earn money and make a contribution.

Here are links to some of the case studies (now held in the UK Government Web Archive).

Christine Dryden – Laundry Assistant

Jon Prashar – Group Head of Diversity Marketing

Ian Hollingsworth – Catering Assistant

Sheena Watts – Nursery Assistant

Louise Whittaker – Administration Assistant

Bianca Raven – Team Administrator

Steven Carter – Trainee Team Leader

Being Mortal: Illness, Medicine and What Matters in the End by Atul Gawande – book review

I heard recently that the local geriatric ward puts a photograph of the patient in his or her prime by each bed. The aim is to help staff to treat their patients as individuals, but it makes me uneasy. Do these people only matter because of what they were, not what they are? Because once they stood proud and handsome in their uniform, or looked lovely on their wedding day?

Professor Atul Gawande has the problem surgically excised and laid out for inspection in one of his unflinching but compassionate case studies:

What bothered Shelley was how little curiosity the staff members seemed to have about what Lou cared about in his life and what he had been forced to forfeit… They might have called the service they provided assisted living, but no-one seemed to think it was their job to actually assist him with living – to figure out how to sustain the connection and joys that most mattered to him.

Gawande is an eminent surgeon. As a young resident he displayed little overt emotion when his patients died, but dreamt about finding their corpses in his bed. Since then he’s toughened up but, with age and experience, begun to see how he and his colleagues fail to have the right conversations with patients, and how this leads directly to greater suffering.

Doctors hate to admit defeat, and the last thing patients want to hear is that nothing can be done. So there’s another round of pointless chemotherapy, or a major and high-risk operation that might, at best, lead to a minor improvement. Among Gawande’s most haunting stories are the patients who say they do not wish to end up living a half-life, “drugged to oblivion and tubed in most natural orifices as well as a few artificial ones”. But when the time comes to make the decision, either they or their loved ones cannot look death in the face; they demand that everything possible be done, and end up in exactly the state they most feared.

Gawande practises in the US, and I don’t believe the worst excesses of the medical system would happen in the UK (God bless the NHS and its budgetary constraints). But many of us fear being trapped on the medical rollercoaster.

It’s not just hospital-based, acute illness: Gawande diagnoses our whole approach to decline, disability, dementia and death as infected with the medical ethos, leaving people isolated and helpless. Health and safety are easy to measure, but how much worth people feel in being alive is not. Institutions focus on being efficient and, above all, safe: residents rise, wash, dress and eat to order. If they might fall they must use a wheelchair, even though that loss of mobility will certainly hasten their decline.

The child of Indian immigrants, Gawande has seen the old ways of old age, where elders were supplicated to, lived with their families and received support to live as they desired. When Gawande’s grandfather was well past 100 he still wanted to ride around his fields each night; cue a family crisis meeting about the old man’s safety? No, they just found him a smaller horse. But Gawande doesn’t sentimentalise the intergenerational model, where carers were expected to sacrifice their own ambitions and family tensions simmered.

This engaging, humane book is best read calmly when we and our loved ones are in reasonable health. It made me reflect on the endings I’ve witnessed so far. Whether the journey from first symptoms to death took weeks or decades, it’s easy to see in retrospect that we were staggering from crisis to crisis, doing our best but suffering from false hope and failing to plan for the inevitable downward spiral.

My mother tells me to put a pillow over her face, which indicates her general attitude but isn’t really a plan. We need to start asking ourselves and each other the questions Gawande finally learnt to ask his patients: What are your biggest fears? What is most important to you? Which trade-offs are you willing to make – and which not?