Harmless remedy or dangerous pharmaceutical?

In Canada, melatonin is deemed to be a "nutritional supplement." It's sold in most pharmacies and health food stores as a natural and healthy way of overcoming jetlag or ensuring a good night's sleep.

In the UK, melatonin is a harder to come by. In 1995, its designation was changed from nutritional supplement to "medicinal product", which meant that it could no longer be sold alongside vitamins in the health food store. Yet - in a classic Catch-22 -  because melatonin was not licensed to be sold as a medicine, was hard to obtain on a prescription basis also (this article describes the late 1990s through to late 2000s system).

Things began to change in in 2008, when the prescription melatonin-based medication Circadin was approved. Other forms of melatonin have also been licenced by the European Medicines Agency, so can be sold in the UK on their European licences. It is also legal to import and sell unlicensed medications into the UK (see here for details) which explains why US-made melatonin products are readily available on-line through sites such as amazon.co.uk. Yet the NHS prescription guidelines still warn "Melatonin is not suitable for everyone and some people should never use it. Other people should only use it with special care...."

Melatonin shows how far medicine is from being an exact science. One might think that there would be some objective criteria for deciding whether a substance is a nutritional supplement or a medicinal product, that Canada and the UK would apply the same criteria, examine the same scientific evidence, and reach the same conclusion about melatonin's safety. One would be wrong.

A regulator risks making two types of mistakes. If controls are too tight, people who have a legitimate use for a drug may be unable to obtain it. If controls are too lax, people may misuse a drug and be harmed by it. Since it's extremely difficult to estimate the unmet needs for a drug or the amount of overuse, let alone the cost of each of these, pharmaceutical regulation is an inexact science.

In this context, history matters. I don't know why melatonin was not regulated when it first came on the market - perhaps because people had less knowledge of the power of hormones back then, perhaps because of the way pharmaceutical regulations were written there was no need to seek approval for a naturally-derived product such as melatonin. But once a substance is readily available, it's hard to take it off the market. There are many regular melatonin users in Canada, and they would demand a pretty good explanation of why they should be deprived of a product that appears to promote sleep without producing any readily detectable harmful side effects.

Melatonin illustrates the fact that the regulation of medicines is an economic choice, as well as a medical one. Some gain from tighter control of pharmaceuticals, some people lose. This is apparent by considering the various players in the pharmaceutical business: governments, private insurers, consumers, and pharmaceutical companies.

Tighter control imposes costs on governments. In Canada and the UK, the public health care system pays for doctors visits. Any time someone goes to see the doctor to get a prescription filled, that's a cost on the public purse.  The UK, as well as some Canadian provinces (e.g. BC and Quebec) have public pharmacare programs, covering the costs of some prescription drugs. Putting a medicine on the list of approved (and paid for) pharmaceuticals might increase health care costs (or decrease them, if the new treatment replaced another, more expensive treatment). (Though governments have an interest in the well-being of their citizens, and presumably take this into account also).

 Private health insurance, in Canada anyways, typically only pays for prescription medications. To the extent that private insurers aren't simply able to pass costs onto their customers, they have an interest in deregulating routine treatments. It's far cheaper (for the insurer) if people buy antibiotic cream, antifungal cream, cold medications or sleeping aids over the counter. Only when a low cost treatment has the potential to prevent high cost treatments down the road would a private insurer be interested in paying for it. 

Consumers' interests are a little bit harder to work out. When a medication is available over the counter, the consumer has to pay for it him or herself, which is a cost. At the same time, it is extremely convenient to be able to buy medications without a prescription. Moreover, even when governments and insurance companies pay, eventually the cost will be shifted back onto taxpayers and consumers. But consumers do not share equally in the costs of paying for public and private health insurance. A person who contributes more than average (pays a high amount of taxes, say) would have an interest in minimizing public costs; a person who pays little or no taxes would have an interest making government health insurance as generous as possible. So, even though consumers have a huge stake in this issue, their interests are hard to work out - see, for example, coverage of the recent US decision to change the allergy medication Allegra from prescription to over the counter here.  

The final group with a stake in pharmaceutical regulation is the drug companies themselves. For them, it's a gamble. Over the counter availability leads to higher sales. At the same time, competition from generics and the lack of a third-party payer puts downwards pressure on prices. For allergy medications such as Claritin, the switch from prescription to over the counter has been highly profitable. For the anti-cholesterol drug Lipitor, the jury is still out. 

It is worth noting, however, that drugs tend to move from prescription to over the counter status at around the time that their patent protection expires. Producers prefer low sales/high price, but when the lack of patent protection puts downwards pressure on prices, they prefer high sales/low price to low sales/low price.

Medicine has all of the trappings of science - the white coats, the degrees on the wall - but it's conditioned by history, custom, tradition and, of course, economics.

Comments

[RPLong]

Patients' access to medicine is the only thing that matters.

Worth noting that if a pharmaceutical product is patented, the PMPRB therefore controls its price, whether or not it is a prescription drug. This price regulation means that it is in the pharmaceutical industry's best interests to have the drug reimbursed, and that can only happen if it's a prescription medication.

So you can imagine how many prescription drugs ought really to be OTC, but thanks to Canada's archaic price-control system, everyone pays higher prices and faces reduced access to medicine.

[Frances Woolley]

RP Long "Patients' access to medicine is the only thing that matters"

Some medicines do more harm than good, either in general, or in specific cases. Given that it's incredibly costly for every person to gather the information that they need to be their own pharmacist, regulation is potentially beneficial. Whether the right drugs are restricted, and whether or not pharmacists should be able to write prescriptions, are entirely different questions.

Whether ir not it's in the pharmaceutical industry's interests to have the drug reimbursed is function of the way that the insurance provider operates - how effective is it at using monopsony power? Note that a number of prescription medications are not covered by private insurance, also.

To my mind, the #1 thing that matters in terms of the price of medications is patent protection. Take, e.g., a drug like thalidimide. Given its potentially deadly effects, there is no way it should be available OTC. At the same time, given that it was invented half a century or so ago, and costs pennies to make, there is no way it should be given patent protection, and sold at an incredibly high cost.

[RPLong]

Prof. Woolley, we are kind of saying the same thing. The PMPRB regulates all patented medicines. The patent comes with a price bump that goes right along with monopoly power. Then the PMPRB further increases the price by increasing regulatory burden and, in many cases, providing a mechanism by which the patent-holder can argue their case for *even higher* prices, using the veneer of health economics.

Some medicines do harm and some do good, and most do both harm and good. It is costly to gather information on an individual basis, but I have also been the one in the position of collecting that same information for the institutions that regulate, and I can tell you that it is equally as costly and susceptible to error. Regulation doesn't improve those kinds of results.

But what we do know is that a variety of countries offer a variety of medicines at varying levels of regulation. Omeprazole, for example, is OTC in the United States but not Canada. Synthetic insulin is OTC (actually "Schedule D") in Canada, but prescription-only in the United States. There aren't very many people killing themselves with omeprazole in the USA, nor with insulin in Canada.

But providing easy access to medicine is a humanitarian issue with economic implications, not an economic issue with humanitarian implications. Or so I see it. Others may differ.

[Wonks Anonymous]

I use it occasionally, what are the downsides?

[RPLong]

Oops, now my memory is failing. I can't remember if "ethical" items are Schedule D or E, but you get the picture...

[Frances Woolley]

RPLong - thanks for that response. The synthetic insulin example is fascinating. I wonder what the politics of keeping it behind a prescription wall in the US are? My guess would be that insulin is used by a lot of elderly and low income people, who might be unable to afford it if it was OTC because it would no longer be covered by medicare/medicaid. But really don't know. If that's right, it's a costly kind of income redistribution.

Wonks - if you click on the link in the post saying NHS prescription guidelines it will tell you the downsides. It makes you drowsy if you operate machinery, it shouldn't be combined with alcohol, and it shouldn't be used long term - my guess would be that artificial melatonin might interact with natural melatonin production. Also some melatonin is extracted from bovine pituitory glands, which may or may not bother you. But you can find that info (consult a doctor before giving to children, not for long term use) on Canadian bottles. I used it last night and feel fine today.

[Shangwen]

Melatonin is an interesting one, but as with many OTC treatment or those marketed more as "natural" aids, how people use them is influenced by their perception of the drug. If people see the OTC product as a drug (Claritin), most people use it with caution. If it is marketed as natural, more people will overuse it. In some situations (vitamin C) this is no big deal. In the case of melatonin (which exhibits a phase response curve correlating with dosage), patients need more information, confidence, and discipline to get the maximum benefit and minimize the downside. And of course price matters too.

One of the benefits of prescribing is that you are being monitored by someone who is focusing partly on getting the dosage right. We always talk as if liberalizing pharmaceutical access will lead to all kinds of dangerous overuse, but patients are just as likely to underuse OTC drugs as a precautionary measure too (e.g., parental reluctance to give kids tylenol).

It doesn't have to all-or-nothing. I would love to see a system where, for example, diabetics were intially prescribed their insulin, and then issued a licence to obtain it themselves once the doc was satisfied the condition was well-managed. This wouldn't work for all chronic diseases, but it would certainly reduce the burden on the patient and increase access.

[Frances Woolley]

Shangwen, fascinating.

I notice that the article you reference talks about 0.5 mg doses of melatonin as compared to 3 mg doses. The OTC bottle I have by my bed is 5.0 mg, which is consistent with the idea that people overdose on natural medications. Or that people have no idea how much to use, and figure that more mg = better value + more effectiveness, so manufacturers up the dosage to increase sales.

A friend is an anesthesiologist. She has been known to refer to the amount of the active ingredient in OTC formulations such as children's tylenol as "homeopathic". I've become much less cautious about popping tylenol (I was probably one of those underusing parents) as a result of her advice.

I agree absolutely with your observation that it doesn't have to be all-or-nothing.

[Determinant]

You asked about insulin. I have special knowledge of it, being a Type 1 Diabetic and have used the stuff for 30 years.

Though insulin is technically OTC in Canada, in practice it is prescription as insurers will not pay for OTC medications. They will however pay for insulin provided a physician has prescribed it. The diagnosis of Type 1 Diabetes or advanced Type 2 Diabetes is hard to argue with.

It doesn't have to all-or-nothing. I would love to see a system where, for example, diabetics were intially prescribed their insulin, and then issued a licence to obtain it themselves once the doc was satisfied the condition was well-managed. This wouldn't work for all chronic diseases, but it would certainly reduce the burden on the patient and increase access.

That's what happens now. I go to my family physician for a prescription renewal appointment once a year. She writes out my prescriptions for my chronic medications (insulin, blood pressure pill, a common as dirt combination for diabetics) with six repeats for a year. Off I go. Some doctors only do one repeat but they are being stupid.

Insulin is not like an antibiotic with a steady dose, you are trying to replicate the intricate regulation of a pancreas through syringe injections. It needs adjustment. For instance I am sensitive to 1 unit changes in my long acting insulin (levemir). Too little and I hit the roof at breakfast, too much and I crash low repeatedly at night and levemir lows are nasty.

On prescription drug access, Health Canada marks part of the Canada Health Transfer as being for "catastrophic prescription drug coverage" but there is no enforcement. All provinces have a catastrophic access program, e.g. Trillium Drug Benefits here in Ontario. But except for Quebec they are all means-tested and subject to classics like the spouse-in-the-house rule. Quebec mandates private coverage through the life insurers, Green Shield or Blue Cross for all employees and RAMQ for those without employer coverage.

Private employer coverage is the main lifter for working-age Canadians. All provinces have Blue Cross plans which offer private, personal drug coverage with varying degrees of underwriting, which means no coverage for people like me. Blue Cross plans in Canada are not-for-profit and act as utilities. Ontario Blue Cross only has "fair" coverage with extensive underwriting as they were financially gutted in a restructuring 15 years ago. Alberta Blue Cross is the only one that offers a no-underwriting plan for non-insured persons, at the province's initiative.

Drug coverage in Canada is decidedly patchwork and spotty.

[Shangwen]

Determinant--thanks for setting me straight on that. Re the CHT: I don't think there's much enforcement of anything there on the provinces. Would the feds really want to? They haven't really owned the Canada Health Act since the Chretien-Martin years.

Re coverage: there is always a lot of talk when a drug isn't "available", i.e., unlisted, not reimbursed, off the market, whatever. But the real issue is that you want people to have access not so much to the drug as to the therapy, that is, the drug plus some system for its prudent and beneficial use. That could be the directions on the bottle, or it could be access to a specialist who is practising wisely. The latter is much harder to guarantee.

[Determinant]

Drugs have been the ugly step-child of the Canadian health system for years. I wish we had the UK system, but we don't. That's why I joined the NDP. Frankly, I care about the availability of insulin and its cost, and would prefer covered insulin and uncovered doctor's visits, but we have the opposite in Canada.

Drugs coverage is where every province and the Feds *feel* they should do something but don't want to spend the money so they try to get the other level of government to spend it. The provinces want CHT money from the Feds (and yes, there is no supervision, they can and do blow it on paving roads), the Feds want to fob people off onto Blue Cross or the life insurers and then that group says they won't do any coverage in meaningful amounts without underwriting and exclusions. Nobody wants to face the hard truth and take ownership of the issue.

The hard truth is that the business of business is business, that is to make money, not to be a welfare organization to provide drug coverage to employees. Plus many company drug plans are so poorly structured that employees are ill-served. I have long realized that my diabetes will not go away when my job does and conversely that my diabetes should not be my employer's problem. If we want a flexible labour market where people find their niche in businesses of diverse size and we want/need people to move around, then moving drug coverage under the government banner is a good thing.

Conversely, disability coverage is well-served by the private market and should remain in private hands. The key to making that market work better is education as the products can be complicated and just like RRSP's and pensions, a personally satisfactory disability coverage package requires a round-out purchase on the private market. But little or no government money needs to be spent.

[steve]

"I've become much less cautious about popping tylenol (I was probably one of those underusing parents) as a result of her advice."

Larger loading doses are now common, especially for kids. However, I would still be careful about total daily dosing as the drug is hepatotoxic. Probably better to alternate with Motrin. (Also an anesthesiologist.)

Steve