You know this is serious business when we get two letters published side by side on the same day from Ministry of Health on the essentially same subject, no thanks to 400-word limit imposed by The Straits Times Forum. This happened on 18 June 22 (Assistance available for cancer patients who need medications not on new list; Balance needed between allowing liberal use of cancer drugs and affordability).
Basically the problem is “money no enough”. But I think somehow the discussion has veered towards subsidising drugs that are “clinically proven” with “evidence”. The words “clinically proven” appeared twice and “evidence” appeared three times in these two letters. The words “cost-effective” appeared three times as well.
So what is “evidence” and “clinically proven” in the medical world? It’s really based on biostatistics and probability. This hobbit has a confession to make, like many medical students in the past, he skipped or slept through most of the lectures in social medicine and biostatistics and remembers only a few shreds of the stuff, now located in some obscure sulci of the brain that has been in disuse for a long time.
The basic principles of biostats, or rather – inferential statistics, are based on proving or disproving “the null hypothesis” with a probabilistic threshold of 5%, hence the dictum that something is “statistically significant” when p<0.05. This requires really obtaining many values for the same trait under investigation (also known as “response variable”), leading to a distribution of values that are often assumed to have a “normal distribution”.
Hence, this concept of the “power” of a study, which is influenced by the number of subjects under study (i.e. sample size) – the more subjects, the more values we can get for the same trait under investigation, and we get more power. (Actually there are 4 factors that influence power, but we will just talk about sample size here).
As you can see, this kind of evidence in clinical depends on studying a group of people. But the idea of precision medicine is predicated on very different premises. Precision or personalised medicine depends on customising treatment or intervention based on a suite of factors that are peculiar to a person, not common to many persons.
If something in precision or personalised person is proven to work well for one person, then that is evidence in itself. To go back to the old framework of submitting lots of “evidence” to show that it works for many people (i.e. “clinically proven”) is just not going to cut it.
Sure, there are lots of people practising stuff close to quackery in the name of precision or personalised medicine, and this should not be allowed at all, much less be covered by subsidies or insurance pay-outs. But to ask for more evidence the old-fashioned way that something works for many people for a given problem is like asking people to buy and use paper road maps on a driving holiday when there are GPS and Google Maps.
But most importantly, to the patient itself, inferential statistics means nothing. To him or her, evidence is when the patient feels better, his cancer marker counts are lower or better still, his tumour is seen shrinking on the CT scan or MRI. To the patient, such “solid” evidence requires a sample size of one – the patient. The idea that someone needs to submit more evidence to show the magical p<0.05 when his cancer markers are dropping and his tumour is shrinking on a CT scan just cuts no ice with the public, or for that matter, to anyone with a modicum of intelligence.
Simply put, the way things are now: – Just as one man’s meat is another man’s poison, one man’s evidence is another man’s quick death sentence (should the treatment be denied).
And then there is this more difficult concept of cost-effectiveness. Cost effectiveness in reality is a ratio of price and desired outcome. The first step is to define what is the desired outcome. In this case, it may well be period of additional survival attributable to the new treatment. The next and difficult step is to apply a dollar value to this additional period of survival and say well, is this worth it?
Inherent in this is that we are saying that there is a price-tag to each day of additional survival. If the cost of the treatment is below this price, we will pay. If the cost of treatment is more expensive than this price-tag, we won’t. And if the patient cannot afford it, then the patient dies. Hopefully quickly and less painfully.
This reminds me of a classic Health Economics textbook written by a prominent American health economist, Victor Fuchs in 1974, titled, “Who Shall Live?”. If you are a health economist or policymaker, implicit in asking this question “Who Shall Live?” is also answering the terrible question, “Who Shall Die?” in economic and policy terms.
But both questions have to be answered because resources are limited. If we had unlimited resources, then these questions need not be answered. But we don’t. That’s the sad truth. Perhaps we should learn from doctors from several decades ago when Singapore had very limited resources. For example, in nephrology, Singapore had very few dialysis machines and doctors had to decide who gets dialysed and who doesn’t, and in the process literally gets to decide who shall live or die.
Maybe the authorities can release a transparent standard of $X per day of additional survival and answer the question of who shall live or die, so that drug companies can decide if they want to meet this target or not and get funding or insurance, especially Integrated Shield Plan (IP) coverage.
This is because the current approach is deeply and intellectually unsatisfying, when the decision to approve or deny funding or insurance coverage for a treatment for a patient comes down to
- Whether a treatment is off-label or on-label (which as this hobbit has said before, what is off or on-label can come down to a rather unscientific basis – like Viagra and pulmonary hypertension)
- Whether a treatment is supported by evidence based on inferential statistics (i.e. based on statistics derived from a group of people) in the era of personalised and precision medicine
Until we have the gumption to just say, “look, some people are NOT going to get funding or insurance coverage for treatment because we cannot afford it and yes, rich people do live longer because they can pay for better or personalised or precision medicine”, then the deep murmurings of discontent and unhappiness will continue to fester.
In the meantime, perhaps IP providers can consider selling riders that pay for off-label use of medicine and personalised or precision medicine. This will be another opportunity for them to make even more money. This hobbit will pay for such a rider if it is just a couple of hundred dollars a year.
I am sorry if this post seems rather dark and amoral. It’s better to be blunt and amoral than to prance around the altars of evidence and on- or off-label use.