Diseases desperate grown By desperate appliance are reliev’d, Or not at all.
[1600-1 Shakespeare Hamlet iv. iii. 9]
There are few more emotional decisions in medicine than the appropriate way to treat a potentially fatal cancer. Perhaps this is why oncologists rely so much on clinical trials to help them decide. At least it can help ensure decisions are made on grounds that are both objective as well as compassionate.
In the past, clinical trials of new cancer treatments have generally begun in those for whom all reasonable conventional treatments have been given. The ethical equation of these trials is not controversial. Informed consent includes discussion of the inevitability of death, with or without the new treatment. The patients who volunteer for them do so out of a mixture of sheer survival instinct (“you never know, it might be the next miracle drug”) and altruism (“my suffering will not be in vain if it helps science figure out how to treat this cancer better”).
But does this choice constitute a human right? Should terminally ill patients be allowed to try absolutely anything they want as long as they can find a doctor who will oversee it? Who should decide when regulatory approvals can be waived or ignored?
Certainly there are some who want to give it a go, as evidenced by the number of ‘Right to Try’ laws being legislated in the USA. On the one hand, we can all empathise to some degree with the trope of the family of a desperately ill patient scouring the internet for experimental treatments while do-nothing know-it-all oncologists in white coats shake their heads and give up. On the other hand, I can see how such laws will open vulnerable patients and their families up to a scale of systematic callous quackery that is unprecedented.
There are more subtle arguments in favour of the RTT laws as well. With the length of time and expense involved in gathering enough evidence to satisfy the Food and Drug Administration (FDA), advocates of the laws argue that terminally ill people can’t afford delays in regulatory approvals. The way the laws work is that they essentially exclude certain treatments from having to progress beyond Phase 1 clinical trials before they can be used on demand by patients. The only requirement for medical supervision in most States where the laws are in force is that a doctor (not even necessarily an oncologist) is agreeable to prescribe and oversee the treatment.
A Phase 1 clinical trial is the first step of a three-step process in working out whether a drug should get to market. The experimental molecule is given to a small group of healthy volunteers and data on toxicity and dose ranges are collected. Phase 2 trials actually involve using the drug on small numbers of people who have the disease in a randomised, controlled fashion to establish efficacy and safety in those who might use it. Phase 3 trials involve larger numbers of patients treated in conditions which approximate the real world. Drugs in Australia are normally expected to have at least one Phase 3 trial in their favour, as well as cost-effectiveness data and trials comparing the new drug to existing treatments for the same condition that are already on the PBS.
Bypassing Phase 2 and 3 trials on demand for individuals represents a massive risk. There is no guarantee at all that the new drugs will even work, since after Phase 1 trials all you really have is a drug that you reckon is a good idea and the knowledge that it doesn’t seem to kill healthy people on the spot. Critics of the laws point out that there are numerous cases of experimental drugs being approved for fast-track use by individuals with terminal disease which have led directly to death well ahead of their prognosis.
Even if you accept, with some reservations, that these laws enshrine patient autonomy and allow doctors to help their patients more effectively, there are still big problems with how to implement such legislation in Australia. For one thing, there is the question of supply. Often new treatments are developed by small biotech companies and then sold off once they can be commercialised. How will small biotechs be able to supply dozens or even hundreds of demands for their unproven molecules? Will these experimental treatments have to be funded by Medicare or by the private health insurers? Most likely it will come straight from the superannuation or savings of the cancer sufferers.
What is to stop unscrupulous doctors from opening up ethics-free practices that prey on the desperation of families of terminally ill people but are technically legal under RTT principles? The legislation usually specifies that State Medical Boards cannot discipline individual doctors for participating in RTT treatments if there are poor outcomes. There would be nothing to stop a sufficiently ghoulish practitioner from making a pile of cash by linking up frightened and vulnerable victims with the latest experimental treatments that might not even work and for which they are not held accountable in the slightest. This sort of revolting exploitation of regulatory loopholes has been underway for some time. Traditionally it has ended with the dodgy practitioner heading to Mexico to escape the authorities. The RTT legislation clears the way for a flock of these vultures to run their rackets without impediment alongside mainstream facilities like major teaching hospitals.
Perhaps most worryingly, widespread adoption of RTT laws as currently proposed could cause drug companies to stop bothering to seek regulatory approval at all for some of their promising compounds. Why spend tens of millions on Phase 2 and 3 trials when you could just start a social media campaign among patient support groups and generate sales by word-of-mouth RTT demands? Let the hospitals and universities fund the difficult and expensive trials that lead to responsible use of new drugs.
The debate goes on, but there could be as many as twelve US states with RTT laws enacted by the end of this year. They have the potential to radically transform the way the FDA (and by extension, the TGA) are allowed to do their job. They may also transform the way that scientific rigour is applied to emotional treatment decisions. Proponents of RTT legislation need to be careful what they wish for. In their grief and desperation, they may erode half a century’s worth of progress in medicines regulation.