Consequences?

The drug shortage is a creeping problem that is not noticed by the majority of patients and practitioners, even when they have been affected.

The biggest consequence, so far in Canada, is on the taxpayer. No one is measuring the extent or impact of the crisis. Death certificates require the cause of death to be a disease — not a shortage of treatment for that disease.

The problem is also hidden by silo-ing in disease categories of drugs. The Media pages show how a flurry of public attention has emerged when a certain category of drug disappears–antidepressants, anesthetics, anticonvulsants, antibiotics, insulin, and cancer chemotherapy. Those affected do not realize that their own painful shortage is part of a more serious problem affecting all drugs worldwide.

No substitutes

Sometimes no substitutes are available, especially in the realm of cancer treatment. Good intentioned people strive to devise formulae for rationing, for choosing who gets what. Inevitably, someone must go without.

The advent of COVID-19 strained supplies of drugs inappropriately touted to “work” against the new virus, but needed for people with other conditions, such as malaria and autoimmune diseases. With border closures, COVID also disrupted supply chains, aggravating access to sources– BCG in Mexico, insulin in Iran. Furthermore the harm reduction programs for IV drug users were increasingly underfunded and the lack of supplies and supports has resulted in an uptick of addictions and secondary infections such as HIV and Hepatitis C.

In 2022-23, a concerted run on diabetes medication for weight loss prompted by social media, provoked a crisis for diabetics who need the drugs to control their disease. By January 2024, WHO reported  that  a rise in dangerous fake weight-loss drugs was linked  to the shortage,

Substitutes

Problems with substitutes include increased expense (see below for specifics) and Danger–either through contamination or because the substitute is not equivalent.

Danger–contamination, disease, and deaths. In the United States, the outbreak of meningitis resulting in dozens of deaths was caused by a injectable made by compounding pharmacies and laced with fungus; it was a direct consequence of the drug shortage (see here). Indeed, compounding pharmacies cite the drug shortage as a business opportunity (for a 2017 example, see here).

A study released in December 2012 shows that children with leukemia treated with substitute drugs owing to the drug shortage have a higher rate of relapse (see here and here). In 2010 Dr. William Schubert in Utah died of a shortage of the enzyme used to treat his rare condition, Fabry’s disease (see here). That shortage, which had been produced by viral contamination, provoked many others to fall ill (see here) and it has resulted in research for new products that can cost up to $300,000 USD per patient per year. More recently, Jennifer Lacognata of Florida went partially blind, was unable to work and lost her home, when Hospira the only manufacturer of injectable Vitamin A stopped making it (see here).

In March 2017, a Canadian study published in JAMA revealed that a shortage of drugs to treat low blood pressure [norepinephrine] in 2011 was associated with an increase in deaths. See Emily Vail et al., or media reports, by Reuters, or here and here and here

In April 2017, two children died in Papua New Guinea for lack of malaria drugs. See here. In November 2017, a child died of thalassemia in Iraqi Kurdistan allegedly from a shortage of drugs created by Baghdad’s sanctions. In August 2019 a decline in survival from bladder cancer was linked to shortages of BCG (see also here). By September 2019, Mexican children with cancer were said to be dying due to drug shortages. In December 2019, 81 people were said to have died of influenza owing to a shortage of Tamiflu, itself a result of stopped production owing to too low price. In July 2021, in the midst of crushing shortages, Lebanon reported the death of a 10-month old girl (here), personalizing the ongoing problem that has affected thousands. During the surge of respiratory infections in the winter of 2022-2023, the UK began attributing numerous child deaths to lack of antibiotics against Strep A infections.

Substitute drugs also lead to errors–sometimes fatal– because concentrations, doses, and volumes change (see here and here). Also the following:

  • During the pandemic of 2020 a list of errors was published in Prescrire, urging the importance of reporting of the problems.
  • During the shortage of kids’ fever medications in Oct-November 2022, mislabelling occurred at a pharmacy in British Columbia.
  • Similarly, analysis of reported dosing errors revealed that they increased during the shortage of children’s medications in the winter of 2022-23 in both Canada and the US (see here, herehere, and here.)

In July 2016, a shortage of cancer drugs caused the American FDA to approve use of substances from a Chinese plant, the products of which had been banned a few months earlier (see here). It is an obscure lottery choosing between no chemotherapy — or potentially contaminated chemotherapy.

But beyond the fatal side effects, considerable suffering arises from the stress and anxiety of losing effective remedies or being given inadequate substitutes (see here and here). A nurse in a psychiatric hospital in Ghana was beaten by an agitated patient when a shortage of drugs arose in that hospital (see here).

A late 2018 study showed that the spread of Fentanyl and its associated mortality is likely due to a shortage of prescription painkillers and of heroin.

An op ed in the New York Times in May 2019 suggested that FDA vigilance over foreign made generics has decreased after a brief period of vigorous inspection–possibly as a consequence of the drug shortage and high prices in North America.

A shortage of oral contraceptives in UK in August 2019 led experts to predict a rise in unwanted pregnancies.

Shortages can also promote drug resistance (see here)

Danger–super-bugs. A report in 2018 explained how the repeated antibiotic shortages could allow the emergence of resistant organisms, compromising the ability to control infections.

Danger–non-equivalence. Substitute drugs are not always identical to each other even when they contain the same molecule. This fact leads to problems for people with chronic conditions — such as epilepsy or bipolar disease. If they have been stable on a certain version of a medication, a substitute can destablize this situation and provoke illness.

Danger – threatened democracy. The shortage has made drug supply a political tool. See this 2017 example from Liberia.

Expense. Drug substitutions often pass unnoticed. A newer, more expensive drug might actually be thought of as better. But that is not always true. See Story 15 at this site for an example. A New England Journal report in April 2017 confirmed that a shortage of BCG for bladder cancer provoked a hike in price for less suitable substitutes and by 2023 studies analyzing the COVID-19 pandemic found the same (see also here and here. Similarly global shortages of AHDA drugs in late 2023, led to price hikes in USA.  Canadian pharmaceutical companies cannot arbitrarily increase prices on their stock, but that is not the case everywhere else. Three 2018 reports on drug prices –one from Egypt, a much reported one from USA [see Media USA 2018]on 18 September and another American report on oxytocin on 6 December– explicitly linked a rise to shortages. The Martin Shrkeli case over raising Daraprim price by 5000 percent and the 2018 hike of nitrofurantoin by 400 percent are good examples. A June  2019 survey showed that the additional labor costs in USA hospitals was at least $359M per year and in October California’s new transparency laws revealed staggering hikes of generic prices.

Patients should always demand an explanation from doctors and pharmacists if their drugs are changed. By 2017, drug shortages were cited as a major factor in the spiralling costs of medications in the US, UK, and many other places around the world.

Seniors, people in hospital, and people on welfare, all have their drugs paid for by the Canadian taxpayer. As long as they are receiving necessary treatment, they are unlikely to complain about a more expensive substitute.

People fortunate enough to have drug plans through their employers will similarly not notice, although eventually their insurance premiums will rise. By 2016, this prediction became a reality for Canadians.

The working poor are most likely to be affected in terms of their health, because they may be unable to afford more they expensive substitutes. If they stop taking (for example) their blood pressure or diabetes or antidepressant medications, they will end up sick and in hospital. In Canada, that again means that the taxpayer and the economy will suffer.

An early 2012 report in the CMAJ shows that about 10 per cent of Canadians do not fill their prescriptions because they cannot afford the medications. Those most affected are people in poor health, the working poor, those without drug plans, and residents of British Columbia.

An acute crisis in February-March 2012, has led to a search for replacements and fast-tracking of approvals, but the replacement drugs will inevitably cost us more.

Some companies perceive shortages as a window of opportunity to introduce new and more profitable replacements. For example in late January 2018, Imprimis set up a vigorous ad campaign to announce that it was “dispensing glaucoma medications on the FDA shortage list.” While having a replacement is desirable, understanding what happened to the old drugs and why the new ones cost more is important.

Insurance. When Canadians travel, they often buy private insurance to cover the costs of unforeseen health-care needs in other countries. A recent change in medication can disqualify the traveller for coverage. The drug shortage — rather than illness– is frequently the cause of medication changes.

Saving Lives?

1. Treatment holidays

In 2011 an Australian shortage owing to viral contamination of an orphan drug for Gaucher’s disease resulted in the discovery that patients can actually benefit from treatment holidays. See here. The shortage produced a natural experiment that allowed deviation from treatment guidelines. It is important to remember that treatment guidelines may have pharmaceutical company influence. See here.

2. Death penalty effects

Since 2011, ethical objection to the death penalty has led to shortage of drugs used in execution cocktails used in the United States. These deliberately constructed shortages differ from the majority — and perversely they could save lives of condemned prisoners. The purpose is to pressure governments to abolish the death penalty. Instead some states (eg Arkansas) have retrenched, rushing to execute clusters of prisoners, and some have used inhumane methods. Others (eg Mississippi) are resorting to hiding their sources — possibily illegal–to maintain the death penalty. See Kendall Grove, here. Other reports are found on page Media-United States. In August 2017, Florida used a new anesthetic drug (etomidate) to execute a prisoner admidst controversy (see also here). Ohio is also changing its drug protocol and executions nation-wide may increase in 2017 after years of decreasing (see here). In January 2018, the South Carolina senate introduced 2 bills: one to bring back the electric chair, which passed in March 2018; the other to protect name of pharma suppliers. The electric chair bills were still being debated in February 2021. In March 2018, Nebraska was accused by American Civil Liberties Association of illegally obtaining lethal drug, while Oklahoma considered using inert [nitrogen] gas to kill condemned prisoners (see also here) and in February 2020 had found a source for reverting to lethal injection after a 3 year hiatus. In April 2019 South Carolina considered bringing back the firing squad and approved it in 2021. another person in July 2019 recommended fentanyl be used for the purpose  (see also here and here).The drug shortage is promoting a political discussion about executions (e.g., Louisiana in July 2018, also here, which continues in March 2019. A jurisdictional spat over FDA’s ability to control execution drugs erupted in May 2019 between it and the Justice Department. Do pharma companies withhold lethal drugs to protect their business reputations–or is it a matter of philosophy of which they might be proud? Canadian-born anesthesiologist, Joel Zivot, has been arguing since at least 2013 that if states insist on executing their prisoners, they should resort to methods other than anesthesia pharmaceuticals that are in short supply.  Repercussions from the EU and other regions that make the drugs mean that none will be available to save lives. Nevertheless in mid 2019, the Trump government moved to acquire lethal drugs banned in Europe for resuming executions that have not taken place since 2003. In late 2019, the Ohio governor deferred the planned Feb 2020 execution of a prisoner for a 1987 murder, to March 2021 because of the drug shortage and fears that the pharmaceutical companies would withhold other drug products from hospitals (also here and here). In September 2021 Ohio again deferred  four executions into 2025 (see also here and here) and again in May 2022. In 2020 someone in South Carolina suggested using opioids since they already kill so many Americans. But later that year reports suggest that it will switch to the electric chair; however, in March 2022 that state (and 3 others) turned to firing squads to kill convicted prisoners (see also here  and here). By  April 2023, South Carolina brought a law to shield identities of anyone supplying lethal injection drugs to kill the 34 people languishing on death row, as the firing squad and electric chair were considered cruel. Meanwhile, in August 2023, it emerged that three states have authorized execution by breathing pure nitrogen, although it has not yet been used.

For an excellent June 2021 opinion column on these matters from  click here.

Here is a brief history of lethal injection executions in USA

3. Artificial shortages of illicit drugs.

In 2017, it was suggested that constructing shortages of heroin or raising prices might reduce use. Two case studies were examined by Andrew Kolodny in JAMA (see also here) — one from UK and one from Australia. Neither study implied that drug use would decline and consequences included greater crime and a shift to other means of intoxication.

4. Beyond humans

In 2014, American veterinarians noticed shortages and price hikes of saline. In 2017 a shortage of tranquilizer –made in South Africa and used in India to manage rhino’s — fell into short supply for market chain reasons.

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While activity around solving access to certain types of drugs is important for individuals, it does not address the root causes of the problem and serves to perpetuate it. It raises further questions.

With its technology and its wealth, why is Canada not an attractive location for a new Canadian-owned manufacturer of generic drugs to replace those in chronic short supply? Why must we be buffeted about by shortages, mostly originating in other countries, within an industry that largely does not belong to Canadians, concerning products, the recipes for which are neither secret nor protected?

Perhaps rather than asking Health Canada, these questions should be addressed to ministries of Industry and Foreign Affairs.

Ask your MP.