Original authors: Amol Verma, Contributors: Jennifer Gibson & Fahad Razak
Published: May 5, 2021
COVID-19 is currently the most common reason people are hospitalized in Ontario and there only two medications that can reduce your chance of dying if you have a severe infection. One of those two medications is currently being rationed.
Tocilizumab is an anti-inflammatory medication that was previously used to treat a variety of immune conditions like rheumatoid arthritis or immune reactions in people undergoing a specific kind of cancer therapy. Tocilizumab was recently discovered to be effective in treating people who are hospitalized with severe COVID-19.
According to our estimates, for every 1,000 adults hospitalized with COVID-19, more than 400 would be eligible for tocilizumab and this could potentially prevent 17 people from dying and 12 people from needing a ventilator. Both the demand for the drug and its benefits might be even greater than this because the new virus variants are even more severe.
Tocilizumab is a specialized medication and has only one manufacturer globally, Roche. COVID-19 has suddenly increased the demand for tocilizumab, creating a global shortage. There are no generic alternatives to tocilizumab, although another similar medication, called sarilumab, may have similar benefits in COVID-19. Sarilumab is a similarly specialized medication and is also in short supply.
According to a survey of 20 Ontario hospitals during one week in early March, 15 patients did not receive treatment with the medication because of concerns with inadequate supply and nearly 30 per cent of centres reported needing additional access to tocilizumab. Importantly, the rules for use of tocilizumab and access to the drug varied across hospitals, creating the potential for inequities across the system.
Drug shortages were a common and increasing problem even before the pandemic. The tocilizumab shortage has highlighted several actions that can help us prepare for future drug shortages, which may be related to pandemics and other emergencies or which may arise for other reasons such as manufacturing disruptions. These reflections are based on our experience in Ontario but have relevance for all Canadian provinces and territories.
First, we have very limited system-level data about the supply and demand of specific medications. This is because drug procurement is not entirely centralized and there are no systems to track medication use in near real-time. A transparent drug inventory system that tracks the supply and use of essential medications is needed to predict, prevent, and manage drug shortages. Once a functional system exists for a core set of essential medications, new medications could be added when unexpected shortages occur.
Second, we should strengthen our ability to return and redistribute medications that are in high demand but may be unused in some hospital or community settings. As with tocilizumab, supply and demand for essential medications is often unevenly distributed. Legislative changes may be needed to permit the reuse of unused drugs and this will require a multi-stakeholder effort but could go a long way to reducing waste and mitigating drug shortages.
Finally, an ethical framework for managing drug shortages is essential. A 3-stage approach proposed by the Ontario COVID-19 Bioethics Table in response to Tocilizumab shortages may provide a way forward.
Stage 1 involves treating as many people as possible by conserving and sharing supply of the drug and increasing procurement and/or access.
Stage 2 involves preferentially directing supply to those most likely to benefit based on existing scientific evidence.
If Stage 1 and 2 efforts are insufficient to meet demand, Stage 3 involves using a fair procedure to choose between patients. In some cases, this could include a lottery system to ensure that the distribution of scarce resources does not exacerbate existing inequities.
The Ontario Critical Care COVID19 Command Centre is leading the response to the tocilizumab shortage in Ontario. They are working closely with federal government to secure additional supply and receiving input from the Ontario COVID-19 Science Advisory Table about optimizing the supply of tocilizumab. They are working closely with hospitals to match supply to need as much as possible.
This excellent example of system-wide leadership offers a road map for a more proactive strategy. Ensuring a stable supply of essential medications and equitable, evidence-based responses to drug shortages could be an important legacy of the COVID-19 pandemic.