Thread by @MPaiMD

News today of shortages of life-saving Covid drugs & HC approval of paxlovid (which will initially be in v short supply too). As a methodologist & a clinician, I wonder… how do you follow evidence-based guidance on drugs when you don’t have any drugs? 🧵 thestar.com/news/gta/2022/…

As Co-Chairs of @COVIDSciOntario’s clinical practice guideline working group, @ASPphysician and I have been thinking a lot about this. Here are our practical suggestions on how to treat COVID-19 patients during periods of drug shortage. 2/n

But first: a recap of how we use evidence to inform recommendations. Think of clinical decision making as a treacherous river. To take care of your patients you MUST cross that river. Clinical practice guidelines can help. 3/n

High certainty evidence (well designed studies at low risk of bias - meta-analyses, well done RCTs) can be used to issue strong recommendations. These recommendations use words like “should use…” Think of them as a sturdy, reliable bridge across that treacherous river. 4/n

Dance across that bridge! Cartwheel across it! Throw caution to the wind! Because for nearly all patients, strong recommendations (for or against a course of action) are a good choice. 5/n

Low certainty evidence (studies at high risk of bias, with methodologic concerns, that don't address outcomes of relevance) can be used to issue conditional recommendations. We say “may consider using…” when the bridge is a little shakier. 6/n

Listen, you’ve gotta cross the river. You have no choice. But watch your step on this bridge, think about the unique conditions you're facing, and be on guard as you cross. Conditional recommendations don't fit every patient. 7/n

Methodologists - and guideline panels - are measured when talking about drugs, careful not to stretch from evidence into speculation. We don’t want to misrepresent the strength of the bridge. It’s misleading, and it doesn’t serve patients/providers/policymakers well. 8/n

BUT what happens during a pandemic? Cases are spiralling, hospital wards are filling up, and there are too many sick and dying people. You still have to cross the river! You still have to care for your patient! What if the bridge is shaky… or there’s no bridge at all! 9/n

In times of extreme drug shortage, we may feel compelled to issue statements in the setting of very low certainty evidence – or no evidence. In the last week, @COVIDSciOntario’s guideline team has fielded important Qs from the front lines with no easy answers… 10/n

How do we prioritize different drugs or drug combos when no comparative studies or network meta-analyses exist? How do restrict use (e.g., through dose reduction, course reduction, or limiting use to certain patients) when no well designed subgroup analyses exist? 11/n

Here's what we DO know: there are clearly limitations to evidence - and to the methodologies we use to assess evidence - in times of crisis and extreme moral injury, in the raging rapids of a pandemic. So what can HCPs and hospitals do if faced with COVID-19 drug shortages? 12/n

We can’t give you a bridge where there is none. That’s intellectually dishonest. But we can talk about how to optimize the effectiveness and equity of scarce existing supply, guided by evidence-based and ethics-informed principles: 13/n

Tip 1: Adhere to guidelines strictly, esp the TIERS. These tiers outline who’s at highest risk of severe disease - who’ll have the most bang for the scarce drug buck. We'll be updating this doc soon, but the tiers will remain: 14/n covid19-sciencetable.ca/sciencebrief/c…

Tip 2: Communicate with each other and with the Ministry to acquire and redistribute supply. Sharing is caring! Healthcare professionals and hospitals are living this motto every day. Shoutout to pharmacists and pharmacy directors, who are driving it. 15/n

Tip 3: Make our guidance stricter by only following STRONG recommendations for scarce COVID-19 drugs. (e.g., Remdesivir won’t be used with HFNC, but will be used with low-flow oxygen) 16/n

Tip 4: Make our guidance stricter by rationing WITHIN TIERS. (e.g., instead of offering mAbs to all in Tier 1 / 2, only offer to Tier 1) 17/n

Tip 5: Make our guidance less strict (yes!) by following CONDITIONAL recommendations for non-scarce COVID-19 drugs. (e.g., Therapeutic anticoag for most moderately ill patients) Use what you’ve got! 18/n

Tip 6: With CAUTION, conserve drug by shortening Tx courses where supported by subgroup analyses within studies, or in indirectly applicable studies. Our panel isn’t comfortable making explicit recs poorly supported by evidence. But sometimes at the frontlines, needs must. 19/n

Tip 7: Use a logic-based mechanism to fairly ration COVID-19 drugs - for example, a simple unweighted lottery system. We talk about this more here: 20/n doi.org/10.47326/ocsat…

Tip 8: Always - ALWAYS - engage your ethics colleagues, engage patients, engage families, engage the principles of justice, equity, non-maleficence, and beneficence. Evidence is nothing without ethics. 21/n

We appreciate the anguish on the frontlines, as we have too many sick patients to care for, and not enough drugs for everyone. Our members understand the clinical realities - because they are clinicians, or because they are patients. 22/n

Talking about these strategies - and doing so in a public forum - is difficult. But we feel we must do so, to let the public know that our healthcare system is creaking under the weight of this wave. And to support our colleagues, who are trying so hard to hold it together. 23/n

If you’re not in healthcare, and wonder what YOU can do, I implore you: get vaccinated and boosted if eligible. More than any of the drugs, vaccines & boosters are the MOST powerful tool to keep you out of hospital with serious COVID. 24/n

And a postscript to the methodologists: I support, apply, and at times have even helped produce the knowledge that goes into systems like GRADE. I am grateful to the fine education I received at @HEI_mcmaster and the incredible mentorship of its faculty. 25/n

This pandemic hasn’t dulled my belief in rigorous guideline methods. It’s helped me understand what happens at the pragmatic intersection of guidelines and healthcare crisis. It’s deepened my love of methodology, medicine, ethics, and sheer clinical ingenuity! 26/n

TY to the knowledge creators and the knowledge users. TY to my colleagues at the frontlines who are stress-testing published evidence and making it work for their patients. I am learning so much, and am so humbled by all of you. Long thread. Time for bed. 27/fin