Safety First? How the Current Drug Approval System Lets Some Patients Down

Andrew Culliford, whose story is featured in the Daily Mail, is one of the estimated 7 in 100,000 people living with Motor Neuron disease, a progressive degenerative disease which attacks muscles, leaving those affected eventually unable even to breathe unassisted. For Andrew, a young father who has a severe form of the disease, it means a two to five year life expectancy.

Like Les Halpin and Jenn McNary, the mother of twins afflicted with a similar rare disease, he has a simple request: earlier access to medicines that might help improve or extend his life.

The US introduced a mandatory pre-approval process for pharmaceutical drugs after over 100 people were killed by an untested drug formulation . Today, each drug must go through a series of strictly controlled trials, including Phase 1 tests on healthy volunteers, followed by Phases 2 and 3 which test the drug and dosages on smaller and then larger patient groups. The process is estimated to cost $500 million per drug and to take 8 – 12 years.

The process is designed to ensure the efficacy of drugs has been scientifically demonstrated to a very degree of confidence, and to ensure that patient safety is sufficiently protected. In many ways it has been a triumph of science and regulation.

But it has been a failure for one small group of patients: those with rare, imminently lethal diseases, for whom there are no existing good treatments. Those who will die in less than 8 years. It is these patients who are asking to have access to untested medicines, and to avoid placebo controlled trials, where half the participants are given no drug at all. Les has proposed innovative methods of patient recording data. I have discussed this proposal previously on this blog , and in a joint paper with Les Halpin and clinicians.

Making changes raises a complicated set of scientific, ethical and policy issues. Is it possible to get useful data outside of randomized controlled trials? How can we encourage and reward drug companies researching rare diseases? If we did change the rules, how would we prevent unscrupulous companies from using this to peddle expensive and ineffective treatments? Should we (and would we have to) trade lower quality research that might affect future patients in order to benefit patients today? Will desperate patients be exploited? These questions must be urgently addressed.

One common objection to any relaxation of clinical trial rules is safety, and that is what I will briefly address here. For example, Ammar Al-Chalabi, professor of neurology and complex disease genetics at King’s College London, is quoted in the Daily Mail as objecting that:

‘Licensed drugs have to go through rigorous trials. Even if an unlicensed drug works in some way, it might kill you in another way or cause problems.’

Of course this is true. But acceptable levels of safety and risk vary according to circumstances. And individuals can make their own assessments of how to weigh such risks and benefits.

Imagine two people are stranded (separately) in a desert with no means of communication. One, Emma, has access to a source of food and water. Her conditions are uncomfortable, perhaps even dangerous, but not immediately fatal. The other, Bill, has no food and no water supply. His conditions will shortly kill him.

Now, imagine both come across an old abandoned helicopter. Neither of them knows how to fly a helicopter. To attempt to do so would be very unsafe, and possibly fatal. Even if they survive the trip, without a map, it may not improve their situation.

Would it be rational to attempt to pilot the helicopter? For Emma, it would be irrational. For a small chance of a better life, she takes a large risk of losing her life completely, or making it worse. For Bill it is entirely rational to grasp even a minute chance of life over the certainty of immediate death.

And even if it is not rational, it should be their decision to make. Perhaps, if we let dying people make these autonomous choices, we will find out if the helicopter is safe to fly. If it is safe to fly, Bill could return to save Emma.

In risk evaluation, as in so much of medicine, one size does not fit all. We urgently need to find a way to assist these patients that offers an appropriate balance of safety and research validity whilst addressing their immediate need for effective medical interventions.

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One Response to Safety First? How the Current Drug Approval System Lets Some Patients Down

  • David Duffy says:

    “…trade lower quality research that might affect future patients in order to benefit patients today?”

    The question is not about autonomy – there aren’t constraints on individuals suffering such diseases taking treatments that are known to be ineffective, except financial ones. It is rather whether the researcher will be any wiser after carrying out a historically controlled trial, unless the treatment is extremely effective.


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