Category: Blog

Why is tamoxifen in short supply?

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?

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.

Drug shortages, again! Politics and brownian movement

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.

A week of winnings

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.

 

 

Medical Humanities

When I retired, Meds 2020 launched a Humanities in Medicine symposium; the cheeky students put my name on it. Cheeky — because I had nothing to do with it. It featured presentations from history, music, poetry, and art, and it was an amazing success.

Even more cheekily they labelled it “Inaugural.” To my amazement a second iteration has just happened, organized by students in Meds 2021 with help from Meds 2022, led by Palika Kohli. I have never taught these people, scarcely know them. I am impressed that they would find time to take on the extra work of organizing a symposium and retain the name of someone unknown.

Dr Karen Yeates (Queen’s MD, 1997) and Palika Kohli Meds 2021 at the registration desk.

The keynote speaker was Ophira Calef who used music, humour, and narrative to describe health-care-system encounters for the disabled. All the presenters delivered their offerings with heart in a packed program. The audience was engaged and the atmosphere inspiring!

They say that it will happen again next year. We’ll see. Institutional memory is short and students are very busy. But in the meantime, lots remarkable encounters to remember. Thank you!


Audience and presentations in Panel 4 “On Being”

Hippochromatic Notes sing an a cappella
wrap up in the Walker Atrium

Students are the best

Queen’s University launched a new event, called Ignite, ostensibly designed to demystify academic life and research to a wide public (see also here). Though retired for a year, I was very flattered to be invited to speak about one of my projects, alongside enthusiastic young physics Professor Ken Clark, who arrived at Queen’s just as I left. To my great surprise, members of Meds 2020 and Meds 2021 showed up too, and we celebrated our little reunion together with this photo.

Thank you everyone!

With Lindsay Mainhood, Andrew Belyea, Hissan Butt, Yannay Khaikin, and Harry Chandrakumaran

A busy year

One year into retirement and it feels like permanent sabbatical–i.e., wonderful!

I completed the book manuscript on Easter Island and sent it off to the publisher, and with Dr. Brian White-Guay and two great students we published a research report measuring the drug shortage problem in Canada – -a spot of work that grabbed some media attention and an op ed, although no sign of anyone trying to solve it yet.

Looking forward to a summer that will entail seeing all four of my grandchildren — 3 boys and a tiny girl born June 19–and more time at the chalet at Lac Mégantic and morning coffee on my dock on Colonel By Lake near Kingston Ontario.

 

 

 

Welcome to my new site

I retired in 30 June 2017. In the last class, the medical students held a beautiful surprise party and presented an amazing video of tributes stretching way back in time, which they have posted online here. It has been a huge privilege to know them, and I learned more from them than they ever did from me.

My colleagues at AMS threw a big party in Toronto and there was a good representation from Queen’s students, former students and colleague Dr. Maxine Clarke.

Since retiring, I’ve been busy completing a book manuscript, working on articles and guest lectures, and enjoying time in Glenburnie, Lac-Mégantic, Switzerland, and the south of France. A commentary that I published in October 2017 CMAJ on bloody sweat (hematohidrosis) went slightly viral, thanks to Kas Roussy of CBC.

This new website is for my current projects now that I’ve moved on from Queen’s University.