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If you participate in a #cancer phase 1 trial, what are the chances of receiving a drug, at the right dose, that will eventually be approved for your cancer? About 1 in 83. Latest from @STREAM_Research. More below: 1/ https://academic.oup.com/jnci/jnci/advance-article-abstract/doi/10.1093/jnci/djaa044/5814931#.Xuz7xWao7Zs.twitter">https://academic.oup.com/jnci/jnci...
Hotly debated issue in cancer research: can phase 1 trials be presented to patients as therapeutic opportunities? In oncology, it& #39;s almost ‘party line’ that the answer is ‘yes.’ I’ve argued that- on principled reasons- they should mostly not. See here: https://doi.org/10.1038/s41571-019-0264-7">https://doi.org/10.1038/s... 2/
Why does it matter? One reason is it relates to how we think of early phase cancer trials. Are we doing a favour to cancer patients by including them in our scientific projects? Or are they doing us a favour by volunteering their bodies? Also… 3/
it matters for consent. and bc it gets to how we think about medical evidence & the moral basis for medical action. The ‘epistemic-ethical’ juncture that makes allopathic medicine an undertaking distinct from, say, pre- or non-scientific medicine. Anyway… 4/
Most people who try to address risk/benefit in phase 1 cancer trials use meta-analysis. All sorts of problems w/ that approach. 1- phase 1 trials don’t use clinical outcomes. No matter what numbers you generate, there are debates about whether they matter clinically. Also: 5/
Also, a meta-analysis spits out a number. Like 5-10% overall response rate. Now you have to ask: is that a therapeutic response rate? Numbers are usually an entry point for debate, not a resolution. So... 6/
We took a different approach. It still involves numbers. But we counted what matters. 1st- we decided FDA approval represents a reasonable threshold by which we can benchmark social standards of therapeutic risk/benefit. 7/
2d, we noted that phase 1 trials often enroll patients with a mix of cancers. And they deliver a mix of doses. So we asked: if you go into a phase 1 cancer trial, what is the chance you will receive a drug *at a dose* that is eventually approved for *your cancer?* 8a/
Footnote: years before doing this study, we posited that if the number was 1 in 10, we could imagine a credible claim of therapeutic value See here: 8b/ https://ascopubs.org/doi/10.1200/JCO.2016.67.9902#.Xuz992AZXk0.twitter">https://ascopubs.org/doi/10.12...
Answer: 1 in 83. Using a far more permissive standard (recommendations in @NCCN) the number is more like 1 in 28. 9/
So let’s think about this. 10-15% chance of life threatening toxicity, ~1 in 200 chance of drug-related death for a 1 in 83 shot at getting a treatment that society deems to present a therapeutic risk/benefit balance. 10/
You might say “but cancer phase 1 trials are different now then before.” Maybe. But we were unable to detect any time trend toward improving therapeutic proportions 11/
Some patients with refractory disease might view these odds as favorable ones. That is fine. Provided the patients understand the odds, I respect that. 12/
But to me, no physician committed to a common allopathic epistemology/ethics nexus could endorse odds that slanted in favour of toxicity and against clinical benefit. That is exactly WHY we do phase 1 trials. To kill 82 regimens to find the 83d that is actually useful! 12/
Caution!! Some limitations to our methods and analysis. example: our study was longitudinal. We can’t rule out that proportions for our cohort are different than they would be for today’s phase 1 trials. 13/
This work was led by my awesome, thoughtful, gentle Chopin-playing Master’s student, Sean Zhang. Worked really hard. One of my best Master’s theses supervised. Proud of him. Power of @McGillBioethics students 14/
Thanks to: @CIHR_IRSC for funding this work. To referees for suggestions. To @JNCI_Now for publishing. Cancer journals often resist stories that question consensus. Thanks to them for having the independence and courage to send out for review. END/
