The Elephant in the Room

Recently, there was a report in mainstream media about how an Integrated Shield Plan (IP) provider refused to provide cover for a patient who was suffering from cholangiocarcinoma. The reason given was that the immunotherapy drug was normally used for breast cancer and not for cholangiocarcinoma. The use for cholangiocarcinoma was “off-label”. (Cancer patient ends up with $33,000 bill after insurer refuses to pay for drug).

Two letters from members of the public (both doctors) were published in The Straits Times Forum on 24 April 22 and then MOH and Life Insurance Association (LIA) subsequently weighed in with letters on 25 April 22.

Military colleges often teach that a country fights a war for usually two reasons:

• It thinks it can win the war, thereby achieving the objectives it has set out for the war, so it fights, or
• If it doesn’t fight the war, the country, culture and society as they know, will be destroyed and it may well cease to exist. i.e. the conflict poses an existential threat to the country.

For example, in the current Russian invasion of Ukraine, Putin is claiming the second reason, but his calculus for starting the war was probably that of the first. Ukraine on the other hand, is fighting obviously based on the second reason.

While the arguments put forth by LIA and MOH are not invalid – cancer drugs can be frightfully expensive and their use needs to be controlled in some way, the elephant in the room in this case is that the patient is alive, and appears to be having a decent quality of life. In other words, the immunotherapy drug Pertuzumab worked.

This is quite remarkable given that cholangiocarcinoma patients often live for several months only and the patient is alive and walking around 22 months after diagnosis. The other salient point is that Pertuzumab was not given callously. It was only given after two other conventional drugs had failed.

The last point that should be noted was that we are arguing over $33,000 for something that worked and gave someone a decent quality of life for many months. Not exactly a sum that will sink the system in Singapore, even though it may be a lot to an individual. Putting a patient on a ventilator in ICU for about a week often costs that much if not more, and as we know, many a time the patient ends up not making out of the ICU alive.

It is true that there is scant evidence that Pertuzumab works for cholangiocarcinoma. But we need to remember that clinical evidence is based on inferential statistics – the science of probabilities based on assumed distribution of values (e.g. the bell-shaped curve of a normal distribution).

Let us now return to this patient at hand, Ms Koh Ee Miang. Probability-based and evidence-based medicine mean little to her. Only one thing matters – either she lives on, or she doesn’t. And at only 45 years old with a teenaged daughter, the will to fight for her right to live on (and again this hobbit stresses – with  a decent quality of life), must be very strong. She will fight. She has to fight. She is fighting based on the aforesaid second reason – if she ceases to fight, death will beckon quickly and she will cease to exist.

And indeed, this is exactly what has happened. She has gone to the press so that her plight gets highlighted. And really, the answers and replies so far from the establishment aren’t exactly useful to her or her oncologist.

What does the oncologist do now? Stop the medicine? Should she not have even given her Pertuzumab in the first place? Just let her be overwhelmed by the cancer after the two conventional drugs failed? She’s 45, not 85…..

And then there’s the issue of off label and on label use. The letter from LIA makes it sound like off label use is always an undesirable thing. But that is simply not true. Whether something is considered off label or on label use may be just a commercial consideration.

Let’s take the example of Sildenafil – what is now commercially known as Viagra. Viagra is now famous for being a drug used to treat erectile dysfunction. But Sildenafil was originally put on clinical trial for use as a drug to treat pulmonary hypertension. However, it was then serendipitously discovered that many trial (male) subjects had erections and viola, Viagra was born.

As far as this hobbit knows, the use of Viagra in Singapore for erectile dysfunction is on label but not pulmonary hypertension. It is not because Viagra is not effective against pulmonary hypertension. After all that is what it was intended for and there is clinical evidence to support this. The drug company just didn’t apply for it with the drug regulation authorities for reasons best known to itself. It could be the market for pulmonary hypertension is much smaller than erectile dysfunction and also because of risk management. When a drug is used off label, the doctor and hospital bears the risk. When it is on label use, that risk is shared with the drug company. Since the market for treating erectile dysfunction is such a big and lucrative one, why should a company take on the additional risk of it being used as a pulmonary hypertension drug?

Whatever the case may be, whatever is on label is at the discretion of the drug company when it puts up the drug for registration with the authorities. The authorities can reject the application because of lack of scientific evidence, but they have no powers to ascribe something as on label if that is not applied for by the drug company.

It is noteworthy that the MOH letter to The Straits Times Forum did not mention on label or off label use. It talked about scientific evidence. Because on label or off label use is not quite the gold standard of appropriate use it has been made out to be. There are many drugs that are being used off label in both private and public sector healthcare settings. It doesn’t mean that off label use is always imprudent or unsafe.

Let us now return to the patient. Since missing Pertuzumab for one session in January, her cancer markers have shot up by about 50%. In fact, it was reported that the oncologist may have to change to another even more expensive HER-2 drug because the effects of Pertuzumab are “waning”.

As Dr Jeremy Lim implied in his letter in The Straits Times Forum on 24 April 22, in the age of precision medicine, (e.g. immunotherapy), some finesse is needed. In evidence-based medicine, all of us have been taught that the 95% confidence interval and p<0.05 are sacrosanct. But 95% is not 100% and what about the remaining 5%? What if somehow something that falls outside the 95% actually works for this individual, do we deny this person care? Especially when we are pretty sure that this denial will lead to a quick and premature death?

This hobbit would like to see if some IP providers will think out of the box to address these issues instead of drawing a line in the sand about on or off label use. For example, it could have covered the treatment for just two to three months to see if the treatment works. If the treatment doesn’t work then by all means withdraw cover. But if the treatment works then it should continue cover but the coverage would be subject to reimbursement caps that are stated upfront.

Personally speaking, I would have thought that the IP provider should have just paid out the $33,000 for a treatment that manifestly worked for their policyholder, a living human being. All IP providers profess to care about their policyholders in their marketing materials and public communications. But here again, this hobbit is reminded that insurance companies are business entities designed to maximise shareholders’ value. Bad press, public opinion or the almost certain prospect of an unnecessarily premature death matter little when their bottom line is hit by about $33,000.