Jacalyn Duffin

Canada currently lists 1748 actual drug shortages at its database right now, some of which it has labelled as Tier 3 — meaning they have a great impact on health care. Among those are five actual shortages of nitroglycerin sublingual medication–5 out of the total of 6 such products currently marketed in Canada.

The earliest of the current nitro shortages was announced in January 2023 by Mylan — and the cause was identified as “quality issues,” although media reports suggest that difficulty accessing the raw materials may be the real cause. By March and continuing into May, shortages were reported for other nitro products, and they were attributed to “increased demand.” This is scarcely surprising: if the most important product vanishes, supply of alternate sources will be stressed. Health Canada sent alerts ( (here).

Canada initially saw an increase in companies making nitroglycerin products, especially in the 1990s — and then from about the year 2000, it has seen a steady decrease in the number of products and the number of companies engaged in its production (source).

The graph below shows the timeline of nitro product launches and declines in Canada. The asterisk shows which products are still marketed. It also shows in blue the 43 reported shortages, documented from 2014, all of which have resolved except the most recent cluster since January 2023. Six of these shortages ended in the completed discontinuation of the product. (My source on the shortages is https://www.drugshortagescanada.ca and information gathered from its predecessor for our 2018 report.)

Since 1962, Canada has had a total of 38 nitro products made by 15 companies over the years. It now has only 19 products still on the market made by 8 companies (actually only 7 companies because BGP was bought by Mylan in 2015; Mylan itself is now part of the new Viatris formed from a merger with Pfizer’s Upjohn in 2020).

The pattern is similar to Tamoxifen and kids Tylenol (which I blogged about here and here) and to beta blockers (which I wrote about here), and it probably applies to many generic drugs in the Canadian pharmacopeia.

When suppliers pull out of a market, any drug will be more vulnerable to shortages because margins in the system have decreased — or vanished. That certainly is one reason for the current shortage of nitro.

But there may be other reasons. Of the 19 nitro products still on the market, 5 are sublingual spray or tablet; 11 are patches; and 3 are for IV use (usually in emergency rooms). Only the sublingual products are currently in short supply, although there have been a few shortages of patches and IV products in the past.

I have several questions about this current shortage

1. Why is it mostly in Canada and not elsewhere (yet)? Is it because our market is small and scant resources are directed to countries with a larger client base? American reports in late March of a shortage of the IV format appeared with little follow up.
2. What were the “quality issues” named in Mylan’s shortage report of January 2023?
3. Why is it only the sublingual products (spray or tablets) that are reported in short supply and not also the IV nitro products or the patches? A shortage of raw materials –especially the API (active pharmaceutical ingredient) –should result in shortages of all the formats. It should also affect other countries.
4. Given, #3, is it possible that the shortage has more to do with the shortage of the pump spray device, similar to what was seen during the Epipen shortage in the summer of 2019? I once suggested that those injectors be recycled. Indeed, Mylan once had a problem with its pump spray device that led to a recall back in 2014. The US FDA list of device shortages has no indication that nitro spray pumps are in short supply — but unfortunately, Canada has no such list.
5. Did changing practice guidelines for the management of angina chest pain play a role in the decline of nitro products as they did for beta blockers? Nitro used to be the mainstay of managing chest pain — but now a combination with ASA, or ASA alone is preferred. Decreasing numbers of prescriptions would translate into decreased demand and the incentive for manufacturing is less. It may have contributed to the loss of companies making nitro products.

As always — we need more transparency about the supply chains. We need Canada to measure the shortages year by year to understand the gravity of the problem and measure the impact of policies implemented to deal with them. We need Canada to lead an international discussion about the causes of drug shortages everywhere. This shortage — and all the others–did not originate in Canada; it cannot be solved by Canada alone.

In the fall of 2022, we saw severe shortages of acetaminophen and ibuprofen containing drugs, especially the preparations for children. I have been responding to numerous requests from journalists to explain it. Actually, reports had been surfacing since last spring. But we were told that this current crisis is owing to an increase in demand. The extraordinary increase in children’s respiratory infections is occurring earlier in the season and with greater intensity than usual. This may be because kids were sheltered by the COVID-19 rules. In other words, we have a double cohort of susceptible children as pandemic rules relaxed. What’s more, parents have been hoarding the meds during the pandemic to avoid being caught short should their kids fall ill.

It is important to remember that these shortages are occurring on top of an already fragile supply chain. Yes, COVID-19 unmasked these problems — drugs to help intubate patients in the ICU, drugs to control infection and help breathing. The border closures meant it was hard to ship the raw materials and the finished products; the pandemic meant factories were working with fewer staff and falling behind. But it has been since 2010 that we’ve been tracking drug shortages in vastly greater numbers than occurred in the past. Also at the time these shortages for kids’ medicines are appearing, we Canadians have more than 1800 OTHER drug products in short supply.

It is also important to know that shortages of the same drugs for adults as well as children–especially of paracetamol (another name for acetaminophen) –are reported in several other countries in Europe and in Asia. It is a GLOBAL problem.

Journalists call us about shortages of meds for kids because it is upsetting and frightening– AND especially because kids have motivated anxious and sometimes angry parents who fuss until they get attention. The same happened with a shortage of epilepsy drugs in 2012 and with a shortage of Epipens in the summer of 2019. Elderly adults with chronic illnesses and cancer rarely have the energy or the familial advocates to draw attention to their plight. Furthermore, in this case, it is over the counter remedies that are missing — so the empty shelves are glaringly obvious.

I have already explained how the decline in numbers of manufacturers leads to vulnerabilities in the supply chain– and I’ve shown how that works specifically for the prescription drugs, Tamoxifen and beta-blockers. Now it is time to apply the same historical analysis to over-the-counter ibuprofen and acetaminophen.

As before, I used the Health Products Database and the drugshortage.ca database (as well as its now defunct predecessor launched in 2012) to explore the number of products marketed or cancelled over time. Companies have been required to report shortages –preferably in advance– since 2017. Only some of them do so.

IBUPROFEN

Ibuprofen was discovered in the early 1960s by scientists looking for a drug that would work like aspirin against inflammation, but with fewer side effects. Aspirin can lead to bleeding in the GI tract; it also hampers clotting power in the blood and it can provoke hearing loss. These problems were regularly seen in people using the drug for arthritis and other chronic inflammatory problems. Aspirin was also associated with a dreadful neurological complication in children called Reyes syndrome.

By 1985 the global patent for ibuprofen, held by Boots pharmaceutical in the UK, had expired — and many other companies began making it in different formats: capsules, tablets, liquids and various doses; sometimes combined with other drugs. The drug was safe for use in kids and had fewer side effects. By 1996 companies began discontinuing some of these products. Discontinuations appeared regularly until they peaked in 2019 and 2021. Sure enough, shortages were reported as early as 2015.

During the 50 years since 1972, 15 companies dropped 42 different forms of ibuprofen in Canada. Eight companies are still marketing 68 different ibuprofen-containing compounds. Unfortunately only two companies (Apotex and Teva) have been reporting shortages at drugshortages.ca, although it is supposed to be mandatory to do so; however, over the counter meds are exempt from the mandatory rule. You have to ask ‘why?’ Since these too are essential drugs, they ought to be on an Essential Medicines List if only Canada bothered to have one. Shortages of any essential medicine should be reported.

NUMBER OF IBUPROFEN PRODUCTS IN CANADA 1972-2022 (by DIN)

LAUNCHED

DISCONTINUED

SHORTAGES

ACETAMINOPHEN

Unlike Ibuprofen, acetaminophen was discovered in the 19th century and has not been patented within the last 50 years, although considerable scientific work improved the safety and quality of the product. With the problems of aspirin use in children, the brand Tylenol (made by McNeil labs — now a division of Johnson & Johnson) became a popular best seller. Overdose was known to cause liver problems, but in general it was safer for treating pain and fever in kids.

Over the course of time, 91 different companies have cancelled 510 different products containing acetaminophen. At the moment 30 different companies are still marketing a total of 241 products containing acetaminophen in Canada. However, only 10 companies are reporting shortages at the moment. But we know that the shortages are so severe that replacement drugs are being imported from Australia and the United States. In fact, McNeil the brand-maker of Tylenol has not reported any shortages of acetaminophen, and has only ever reported 4 shortages of entirely different drugs — 2 of which were resolved; 2 of which were discontinued. Janssen, another Johnson & Johnson affiliate making prescription drugs, reported 3 shortages of Tylenol with codeine and 1 with tramadol, all of which ended in discontinuations. McNeil ignores Canada’s rules for mandatory reporting of shortages perhaps because it designates itself as an over-the-counter manufacturer (see above). You would think it would view its product as important and therefore it would be equally important to notify when it is unavailable and when supply will be restored.

To prepare a chart for acetaminophen like the one above for ibuprofen, I would have to click on and open every single one of the 741 files at the Health Products database. I’m not going to do it. I predict that it would look a lot like the chart above: a hey-day period of companies rushing in to produce various formats, a financial-crunch period of abandoning, and more-recent period when shortages appear. Health Canada could easily do it for us. Why don’t you ask them? Here’s the website.

In total there have been 202 shortages of products containing acetaminophen reported by 26 companies since at least 2014. Of these, 132 (65.4%) were resolved, 49 (24.3%) ended with discontinued products, and 21 (10.4 %) are still current. It is interesting that there were MORE acetaminophen shortages reported in 2020 at the height of the first wave of the COVID-19 pandemic than are being reported now. Perhaps they did not involve kids preparations to the same extent, or perhaps there were other even more pressing concerns at the time.

NUMBER OF SHORTAGES OF ACETAMINOPHEN PRODUCTS / YEAR, 2014-2022

This exercise shows–once again–that from once having a multiplicity of makers with a lot of margin in sources of drug supply, we have fewer makers. The change means that any cause of stress in the system–increased demand, shortage of raw materials, difficulty shipping, or factory slowdowns–will provoke shortages. It also shows that many drug companies who have the privilege of marketing in Canada ignore Canada’s rules about reporting their shortages and the reasons for them.

To fix the problem of drug shortages, we need more transparency in the system. We need Health Canada to provide annual reports measuring the shortages. We need an Essential Medicines List. And we need to engage in and lead an international conversation about this global problem.

First we diagnose, then we treat.

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Retired folk are supposed to volunteer. But I was not motivated to do so until the COVID-19 pandemic, when our local KFLA public health unit put out a call for help in contact tracing late in 2020. Apparently more than 200 people responded to the appeal — and about 20 of us were chosen, most retired health care professionals–nurses, doctors, and pharmacists.

We were required to follow an online course, and then attend two days of training before being unleashed on the telephones and computers to perform our tasks. My usual shift was all day Fridays. Sometimes I’d fill an extra shift in surges or when other workers were away. A massive database kept track of all the people who had been in contact with a “case” (i.e., someone who had tested positive). We would pick up the tasks each day, one by one. We had to inform the contact of their exposure (if they did not already know) and explain what to do: how to isolate, how to manage within the home with housemates and family members, when and where to get tested and how often. Then we charted our work in the computer database and made new tasks for follow up. When I started, the isolation period was 14 days from the exposure — it grew shorter over the year that I did the work. Vaccines came in the middle of the year and the rules changed accordingly.

The calls mostly went well. Sometimes they were contentious or upsetting as contacts could be frightened, angry, or overwhelmed. Often we supplied information about financial supports and how to obtain food or medicine during isolation. The information that we gathered was subject to privacy laws, which we all understood from our earlier employment. We spoke with essential workers, teachers, daycare workers, parents of school kids and hockey players, immigrant families, university students and professors, grandmothers, farmers, police officers, partygoers, and, sometimes, our neighbours.

Although we worked individually in separate booths, wearing masks, using lots of sanitizer and disinfectant wipes– there was a certain esprit de corps — we were a team. For most of us, it was the only outside human contact that we had during the lengthy lockdowns.

The regular staff were nice to us, explained what was happening, and they were excessively grateful for what seemed like a modest contribution. Sometimes we made calls to other parts of Ontario if their local services were overwhelmed. We learned that Kingston was the only region to use volunteers and that some health units had given up tracing contacts when case numbers were too large. We sometimes felt a bit smug.

Then omicron entered Canada through eastern Ontario — and we too were overwhelmed. From being the best in the province, Kingston briefly became the worst. And soon it was clear that vaccines did not prevent the infection, although they certainly made a difference to the severity of the illness. Case numbers exploded and the number of contacts spiralled beyond measure. A test was needed to come out of isolation, but appointments for tests were scarce because so many people needed them. People with symptoms were told to simply assume it was COVID and stay home. Without tests, positive cases went unrecognized, consequently, contacts could not be identified for tracing. Our shifts were cancelled at first week by week, then definitively. Ironically, the worse the pandemic became, the least we could do.

It had been a year of dedicated work, interesting, sincere, fulfilling…and yet, I wondered if we had accomplished anything at all. The tyranny of negative evidence: you cannot measure what did not happen.

Once the omicron situation came under better control, we were invited to a little lunchtime reunion. Here is some of our team… I am fourth from left. Our amazing leader at the top.

A potential treatment for COVID-19 exists but is unavailable in Canada, and the government won’t examine the evidence. Why? 

Having chased the drug shortage for more than a decade, I am used to being baffled. But the shortage of ivermectin has me more perplexed than usual. Coupled with what I’m observing as a volunteer contact tracer, this shortage is also alarming. Mounting evidence suggests that the Nobel Prize-winning drug, ivermectin, can also prevent and treat SARS-CoV-2 infection.

Since early January, Dr Kanji Nakatsu, retired Queen’s University pharmacologist, has attempted to alert public health, political leaders (provincial and federal), and the public of the potential value of ivermectin for COVID-19. He warns of the limitations of putting all our eggs in the vaccine basket. But he has received only “thank-you-for-your-message” replies. So, he has launched a petition urging the government to “urgently examine the evidence in favour of ivermection and give due consideration to making ivermectin available immediately to Canadians.” You can see and sign it here.

Dr Nakatsu’s rationale is based on our situation and on the evidence.

Situation: The pandemic will be with us for some time, during which we are all vulnerable. Vaccine protection takes weeks to develop, many won’t receive the shot for months, and we still have no plan for protecting children. Meanwhile, new more contagious and aggressive variants are spreading and may resist current vaccines. Yet as we enter a third wave, some provinces are opening up. More people will fall ill, and more variants arise. We should be interested in anything that might help manage this scourge.

Evidence:

• Ivermectin is safe. A third of the world’s population (2.5 billion) has taken it for parasitic infections. In almost thirty years from 1992, the World Health Organization and Uppsala University VigiAccess pharmacovigilance database report only 16 deaths and 4673 adverse effects.

• Ivermectin is readily available, sometimes without charge, in several countries, including Argentina, Bangladesh, Belize, Bolivia, Brazil, Bulgaria, Czechia, Dominican Republic, Egypt, El Salvador, Guatemala, Honduras, India, Iran, Japan, Lebanon, Mexico, Nicaragua, Panama, Peru, Portugal, Slovakia, South Africa, Venezuela, and Zimbabwe.

• Owing to this ubiquity of use and the reduced COVID-19 impact some of these same countries, multiple trials have examined ivermectin as prophylaxis and treatment (summarized here) Dr. Tess Lawrie founder of the British Ivermectin Recommendation Development Panel conducted a World Health Organization analysis of these trials concluding that ivermectin use corresponds to 86% fewer cases and 68% fewer deaths. She argues that future studies could refine dosing but should not use placebo control because it would be unethical not to offer everyone some of the active drug. 

• Ivermectin is already approved in Canada as an anti-parasitic; it is generic and inexpensive. 

But there is more. 

Merck, the single licensed producer of Canada’s human formulation has let it slip into shortage and does not expect re-supply before 31 December 2021. Numerous over-the-counter veterinary preparations are advertised online, tempting risky behavior.

While ivermectin carried Satoshi Omura and William Campbell to the 2015 Nobel, some say that the honour was conditioned not only by excellent science and effectiveness, but also by the remarkable way in which this drug was distributed. After all, the idea of extracting an antimicrobial from streptomyces bacteria was already well known and had garnered a Nobel in 1952. It was the generous distribution that was novel and effective: its maker, Merck, distributed it free or at low cost to nations plagued with the dreadful diseases of river blindness and elephantiasis. 

Now Merck is promoting a shiny new antiviral drug, molnupiravir, which is potentially more lucrative, although its trials are not especially convincing. Has Merck lost interest in its own reliable but less profitable ivermectin? Could it be that having no ivermectin makes us more likely to purchase the expensive new antivirals? Curiously, however, in the best scenario, the much-touted remdesivir appears to be far less effective than ivermectin.

What’s more, a bizarre coalition of naysayers, including the American FDA and Europe’s EMA, are throwing shade all over ivermectin, citing dangerous side effects and foolish overdosing, and casting aspersions on extant trials. Pressure may be coming from the pharma industry. JAMA recently published a notoriously underpowered trial and in an unusual, late move, Frontiers in Pharmacology rejected an ivermectin trial that it had originally accepted. Why?

It feels awkward to allude to conspiracy theory–and even worse to seemingly promote apparent snake oil. Nevertheless, I’ve got to ask: if the trials are not robust enough, why doesn’t Canada conduct a good trial and settle this matter once and for all?  We will soon have enough cases in the burgeoning third wave to provide a viable proving ground. 

Arguments that this innocuous drug may be lethal are derisory. Let’s get real people: one can overdose and die from over-the-counter Aspirin or Tylenol. We are grown up enough to read the labels. But to get ivermectin and have it sporting a proper label, we need Health Canada to study the evidence, alter the indication if justified, specify the dose, and above all explain the shortage and fix it. It’s COVID-19 that kills people and life as we knew it.

Update June 2021 to June 2022

Dr Nakatsu’s petition received almost 5000 signatures and by 1 June 2021 it was presented in the House of Commons with no change in its status or shortage in Canada. A reply was expected by mid-July, but when the September 2021 election was called, the petition died.

On 17 June 2021 a Cochrane-standard meta-analysis of ivermectin for COVID-19 supported its use (see here).

On 23 June 2021, Oxford University announced that it has launched a large-scale research study to assess ivermectin in COVID-19.

By July 2021 certain scientists were claiming that evidence in favour of ivermectin was either sloppy or fraudulent.

In September, to counter these criticisms, some pointed to the favorable outcomes in Kerala India after ivermectin use had been authorized, although no study was produced to document or confirm its role.

Disappointing results continued to come from trials held in the following months. In May 2022, a study of more than a thousand patients, published in the New England Journal of Medicine, showed that early treatment with ivermectin made no difference to the course of the disease.

By June 2022, a study reported (pre-publication in the New York Times) by Duke University and Vanderbilt University, tested more than 1,500 people with Covid, about half getting the drug and the others a placebo; ivermectin made no difference. However, the authors reported that 90 people with severe disease seemed to fare better than those on placebo–although the differences were not statistically significant. The authors promise to keep studying the drug at higher doses, given its “favorable safety profile and continued public interest.”

Others continue to either cite or criticize the reports by Tess Lawrie, Andrew Hill, Pierre Kory and Peter McCullough. Failing to advance the ivermectin concept, the latter has coupled his advocacy of the drug with misinformation about vaccines, provoking a lawsuit from his former employer, Baylor.

An organization in Canada tries to help people find supplies of ivermectin, at the same time, it discredits vaccines, which casts doubt upon its advocacy of ivemectin. Meanwhile, those desperate to have access to the drug have taken to using veterinary preparations, leading to dangerous overdosing and a shortage of the drug for its approved purposes for animals and caution from the FDA.

Ivermectin remained in short supply in Canada even for its original uses until 19 May 2022. Meanwhile molnupiravir reached completion and received FDA approval for emergency use in late 2021, despite slim to no evidence that it actually works. The UK, Bangladesh, and Israel followed suit. It is still under review by Health Canada.

27 November 2020

The spectre of Erin O’Toole and Michelle Rempel complaining that Canada will not be first in line for vaccines made in other countries is a rich example of political haymaking and hypocrisy. 

Canada used to have a vibrant pharma industry. But its decline can be traced to the actions and inactions of Conservative governments, beginning with Brian Mulroney’s Free Trade Agreement, continuing through to the Harper government’s utter failure to take any action at all on the chronic drug shortage problem that has plagued this country since 2010. Despite repeated warnings that we need to look to our drug security, Canada finds it more convenient to allow other nations to handle that task for us: countries with lower salaries, no benefits, and more lax environmental rules.

Justin Trudeau told it like it is. We have no ability to make vaccines, and only a shred of our former prowess in the drug-making domain. Notwithstanding Rempel’s stunning accusation that Health Minister Patty Hadju would be responsible for more deaths, neither she nor the PM caused this pandemic. 

It was caused by a naturally occurring virus that had long been predicted, and it is spread by politically distorted behaviors in response to controls, while the problems in managing it stem from politically motivated decisions in the past.

Our book on SARS is fully open-access online.

Thanks to McGill Queen’s University Press!

Jacalyn Duffin, as editor with Arthur Sweetman, SARS in Context: Memory, History, Policy, McGill Queen’s University Press and the Queen’s School of Policy Studies, 2006 Full text online here

This month the news has been full of tamoxifen shortages. The drug shortages continue, but Canada is doing nothing about it! Not even measuring it, in the manner that our little team demonstrated last year.

Since October, Canada, USA, England, and other countries are hearing about worrying shortages of tamoxifen. It is a trusty, old, reliable drug that helps to keep breast cancer under control for around half of the people diagnosed with the disease. Normally, they take the pills for 5 years after surgery and/or chemotherapy.

Unfortunately at the time of writing, no fewer than 1960 other drug products are also in shortage according to the government’s database (licensed to Bell Canada). This site is simply a list that is never analyzed or summarized. The shortages include other important cancer drugs, such as vincristine for childhood leukemia, BCG for bladder cancer, and etoposide.

I am often called upon by journalists to talk about this and other shortages. I always agree to do so because we need people and government to be aware. We need more openness and information. This week it was CBC.

Reporters always ask about the cause. Honestly after a decade of chasing the answer, I still don’t know why we have these shortages–or why they came after 2009 with its economic crisis. Seventeen robust potential causes are listed and explained at my website. Many of them have to do with the international market. To know which cause applies when, and to what drug, is beyond me.

Lately it is apparent that the prices of generics have fallen so low (simply by not being raised through time) that their manufacture is unprofitable. Companies simply drop out. The case of Tamoxifen seems to illustrate this point well. I published a similar study of beta-blockers in the CMAJ in September 2019, although changing practice guidelines may also have played a role in the case of beta-blockers. Not so, for tamoxifen which is and has been a mainstay of breast cancer care for more than three decades.

Since 1985 when the patented version of tamoxifen was released in Canada, a total of 11 companies have licensed and sold the drug in this country at one time or another. (This information is available at the Health Products database.)

Between 1996 and 2010 there were at least eight different suppliers. But gradually companies stopped making the drug; seven companies have dropped out since 2003. And of course, by 2014 we started seeing shortages (The shortage information is available at the current shortages site and its predecessor, no longer accessible, which we downloaded in 2017 for our 2018 report).

Sanofi, the first company to licence tamoxifen, dropped out in 2011 after 25 years. Now there are only 3 companies still marketing tamoxifen in Canada: Apotex, Teva, and Astra Zeneca. They have been in the tamoxifen business 30, 29 and 23 years, respectively. They make 10mg and 20 mg doses, but Astra Zeneca dropped its 10 mg dose back in 2003. See the graphs above.

As for the price of tamoxifen, it is difficult to obtain older information. The provincial formularies offer the best source for current prices, but most provinces do not keep old formularies on the web. Newfoundland is exceptional in that it has a digital archive back to 2010–not very far back when we want to know the price since 1985, but better than nothing. The price in Newfoundland has been similar to that elsewhere in the country. Right now generic tamoxifen is listed at 19 cents for 10 mg and 38 cents for 20mg tablets.

Recently Alberta has even seen a small decline in price in terms of real dollars between 2015 and 2019. But the cost of living has increased. So expressing this information in dollars of equal value (thanks to the Consumer Price Index) shows that the generic price has indeed been declining in constant dollars. See the graph above of recent prices in constant dollars.

Thanks to the help of Dr. Joel Lexchin, I have been able to get the price of Tamoxifen in Ontario since 1985. It was first released at $1.34 for a 10 mg tablet ($2.88 in 2019 dollars). It fell steadily to the current $0.1705 per 10 mg tablet. Remarkably the list price of generic tamoxifen has not budged since 1998. See below–graph of number of companies (same as above) with the price of tamoxifen in constant dollars. We can only assume that in the 20+ years since 1998, the cost of making it (raw materials and labour) must have risen at least somewhat. Doesn’t that mean the profit margin will decline?

Key: number of companies (orange); price (blue)

When there are only a few makers, the margin in the system is narrow. Any manufacturing problem will result in shortage. The remaining companies (if any) will encounter a big, unexpected increase in demand and they too will report shortages. Anger against the companies that are making the drug is somewhat unfair; at least they have not dropped out… yet, and we hope that they won’t.

Any normal commercial entity would want to supply and sell its product if it could. But we as a society accept the notion that drug marketing and drug development belongs in the private sector. We also regulate the price. These private companies are not charities; if they are losing money, they stop making the drug so that they can keep paying their employees and their stakeholders.

As for why we are hearing about Tamoxifen, in particular, when so many other equally life-saving drugs are missing is a very interesting question. Sure, it is used to treat a very scary cancer, but experts reassure us that missing doses for a few weeks is not as risky as many fear. So some of the explanation comes from the articulate, motivated, frightened, and basically healthy people who are affected– the vast majority being adult women. They are able to draw the attention of journalists and policy makers and (hopefully) industry and government. It would be wonderful if this energized and effective cohort would remember all the other patients who are coping with dreadful shortages–children, the mentally and physically disabled, those in poverty–when their own issue is resolved.

Florida plans to import drugs from Canada (with President Trump’s approval) and Senator Bernie Sanders will join a diabetic crusade looking for cheap insulin to highlight the evils of the pharma industry. And now a group of respectable Canadian associations is demanding that the government clarify how it will safeguard our already unstable drug supply.

A number of Americans states have introduced legislation to permit importing “cheap Canadian drugs” as a way of lowering costs, ensuring supply, and sending a message to “big pharma.” Some people believe that the so-called “cheap Canadian drugs” might be unsafe; when they point to internet sites, they might be right because many of those web-based sources are not Canadian at all. Other kindly and better informed folk have worried that this action could exacerbate the ongoing drug shortage in this country–as if there are no shortages in USA (there are! lots!).

Referring to our 2018 research on drug shortages, the 25 July 2019 warning letter to Canada’s minister of health is signed by representatives of 15 medical associations, pharmacy groups, and health-care distributors and advocates, led by the Canadian chapter of the Washington-based, international Alliance for Safe Online Pharmacies–Global. The alliance is non-profit, but its members are not, being pharmacies, distributors, and pharmaceutical companies. One cannot help but wonder if they perceive threats to their business model, as well as to the drug supply. Nevertheless, clarity and assurances are a good thing, and I have added import-export to the 16 other robust and (alas) hypothetical causes of drug shortages listed at my website.

But drug shortages are a much older problem than this import-export issue. I have been running my drug shortage website now for eight years, since August 2011. The problem continues unabated–media reporting is inconsistent and incomplete, and consequently, the solutions are merely stop-gap at best because the causes are still obscure. It is a global problem: the website features reports from more than 100 countries. But Canada has been dithering in brownian movement. Unlike the USA, it isn’t even measuring the problem.

One of the much-debated “causes” of shortages is the price of generic drugs — both too high, and too low. Health economists in Canada claim we pay too much for our medicines–but journalists in the United States are convinced that drugs in Canada are “cheap.” Bernie Sanders contends that our low drug prices are owing to medicare– but alas, drugs are not covered in our medicare system–at least not yet. The price differences must lie elsewhere.

But these recent American policy gestures miss the point. First, Canada has almost no drug manufacturing industry of its own. The biggest Canadian generic company– Apotex –manufactures most of its drugs in factories outside Canada. For the rest we buy from American, European and Asian firms — just like everyone else, just like Americans. So what exactly are the “Canadian” drugs?

Second, Canada regulates its industry, as does US FDA, for safety — but unlike the US, Canada does not allow drug companies to raise prices arbitrarily, for example, when shortages arise. Furthermore, firms obtaining a licence to sell medications in Canada have an associated “duty to supply” as part of the contract. While this obligation is seldom policed, it exists as a respected industry standard and can be enforced. Drug companies licensed to sell in Canada must abide by these rules. In exchange, Canada keeps its commitment to drug companies not to sell on the products that it agrees to purchase. In other words, except in individual cases, the drugs available in Canada are at a fixed price, supposedly promised in supply, and not for sale across the border.

So what should the USA and Canada be doing? First, rather than condemning the pharma industry, the USA should be negotiating lower prices– “better deals” (sound familiar?)– with the very same companies who supply Canadian drugs. Second, it should be “regulating” even if it means more of that odious government interference that right-wingers cite as the red-peril threat to free market enterprise: prices should be fixed and duty-to-supply respected. Essential medicines are not like commercial widgets — or at least they should not be treated that way. Third, if drugs are in short supply, why go poaching? Why not make more? And what does this current political babble have to do with the launch of the creative and growing American non-profit Civica Rx ? Rather than objecting to international trading, why doesn’t Canada likewise begin making the drugs that we need with generic companies of its own?

As for the political stunts– e.g, dozens of Minnesota patients coming to buy their drugs in London, Ontario, or Senator Sanders looking for insulin in Windsor–they are just that, stunts intended to grab the fickle media spotlight for personal advantage. And they are misguided. Busy and ethical Canadian physicians generally will not write prescriptions for anyone without an examination, and whatever the visitors can manage to acquire will not make a great deal of difference to our own already stretched supplies.

Instead, we should all be urging Canada, the United States, and other nations to manufacture more of the needed drugs at reasonable prices and to engage in an international project–perhaps through the OECD or the WHO or the WTO–to investigate the drug industry, the supply chains, the middle managers, and the outrageous variations in prices, and to thereby uncover the causes of the drug shortages. Only then can we hope to fix them.

UPDATE March 2020

Comment from Government of Canada on proposed FDA rule re importation of drugs [it is opposed], Canadian Embassy Washington DC, 10 March 2020.

Within five short days I was given two big awards — one from historians, and one from doctors. It is both gratifying and humbling to be recognized by peers for contributions to our shared endeavours–but it is also daunting. I don’t feel like I am done– I am not dead yet–and still have more to do and say; however, I am old now, four times a grandmother and far less time lies ahead of me than behind. Fortunately my husband came along to both events, as always keeping me grounded when nerves take over. I am so grateful to the people who nominated me for these awards, imagining that I might be a contender.

The first was the Genevieve Miller Lifetime Achievement Award from the American Association for the History of Medicine, an organization through which I have had the best of scholarly feedback on my research and where I have found fellow travellers and soulmates. I think it was the first time it had gone to a Canadian. My remarks of thanks and advice are here. They were little different (though shorter) from what I’d said in June 2017 when AMS gave me that fabulous potlatch dinner. Retirement for a historian means not only will you qualify for the Miller award, but you can also keep on working and create a job for young person. Apparently some old people did not like these words at all and were vocal about it on Twitter and elsewhere.

The second was the formal induction into the Canadian Medical Hall of Fame at a lavish, sit-down dinner for 500 people in Montreal. There were six of us inducted, including the late Brock Chisholm, a Canadian military psychiatrist who was the first head of the World Health Organization. His granddaughters were there to accept with eloquence. The organizers had prepared a professional video about me and my work, which is now up on youtube. Again my husband video’d my remarks of thanks and a confession, sincerely meant. We could choose the music that played as we walked to the stage — and I chose an orchestral piece from Handel’s opera Acis and Galatea, as produced and directed by my brother Ross Duffin with his students at Case Western Reserve University (listen here at 4 min 30 sec). We also heard snippets of Lara’s Theme from Dr Zhivago and John Lennon’s Imagine— chosen by the other laureates. 

In the aftermath of the celebrations, Dean Reznick and Andrew Willson made a blogpost picked up by the Queen’s Gazette and Lisa Xu did a write up for the Whig Standard newspaper.

Winning awards is on some level a lottery despite the best of intentions of any selection committee. And choosing one person out of dozens of worthy candidates is difficult. Many people collaborate to create new solutions — as all the laureates made clear in their remarks: they did not get there alone. After a couple decades of teaching my course History of the Nobel Prize: Who Won It? Who Didn’t? and Why? — I had come to see awards as highly political, contingent on context of times and place, and often recognized, in retrospect, as mistaken. I have also marvelled at and tried to understand the pervasive human proclivity to create and venerate heroes, saints, and leaders.

So when these two awards came to me, my former students were laughing. I was being punished for having been irreverent. Suitably chastened, I accepted on behalf of medical historians everywhere, who “get it” that history is important for current medical practice; it will not prevent future mistakes, but it helps us to understand the present, and why things that seem wrong now, were once seen as right. It is the first step to making credible scientific and policy change. It prepares the way for lifelong learning. Every medical school should have at least one historian to advocate for history as a medical research discipline in its own right and to make future doctors skeptical about the durability of everything else that they are being taught.

Me seated on right with the other 2019 laureates and the medical student winners of the CMHF awards. Note Hissan Butt standing 3rd from right Queen’s meds 2020.