Please note I am speaking only for the world of oncology as that's my practice focus and what I know best.
> But I'd like to hear your thoughts on the broader argument of being more aggressive with trials in general. What sticks with me each time this argument comes up, regardless of the particular situation, is this idea that despite some mechanisms for accelerated approvals, we are still far slower than we could be, if we take into account the number of people saved by bringing therapies sooner.
Everything in medicine is trade-off. On the extremes we can practice with no regulation and have immediate access to treatments without evidence accepting that many patients will be harmed as many new treatments are inferior or require phase IIIs on the other end and minimize harms but accept that delayed care will itself cause harm.
Current practice is somewhere in the middle, depending on various factors like efficacy, risks/harms, and alternatives many treatments enter practice after phase I/II or used off-label for close indications.
I like where we're currently at for oncology and don't think we need to change much in the process. The bigger hurdle is funneling those R&D $ into high yield research and perhaps making the cost of trials easier (e.g. research alliances, IT infrastructure to simplify multi-center studies and patient recruitment, ?active government involvement).
There's always fine tuning of that balance that can be done and some cases will prove things wrong on either side of the argument but generally speaking I think we're close to where we need to be. Definitely better than when we didn't have the current approval process.
> It's the counterfactual that makes the argument, the people who do not receive treatment due to delay seems to vastly outnumber the people harmed by experimental treatments.
I don't think this is true and I have not seen evidence to support this claim. There is ample evidence of failed treatment options or treatment causing more harm than good. An example I'm well-versed in is HIPEC for advanced ovarian/peritoneal cancers (we've been doing this for years and it turns out it doesn't do much other than excessive morbidity) or Y-90 for HCC/colorectal metastases to the liver (first trials negative and we recently found out "oops we've been underdosing this and measuring non-target dosing to the lungs incorrectly") both of which are for palliative patients with no good alternatives.
Going back to osimertinib as the example, the main criticism of earlier TKIs (same class of drug, and even osimertinib for that matter) was that the promise of limited data (progression free survival rather than overall) led some patients to get TKI therapy rather than platinum based chemo which was standard of care and has proven OS benefit. Except when the OS data came out it was an "oops, OS didn't pan out like PFS" and people were harmed.
That these happen in the current system strongly suggest patients have access to experimental therapies and that we're not being overly stringent, or this data wouldn't exist.
I would also say that a large proportion of the patients I've interacted with that have disseminated disease are on some trial for experimental therapy with the caveat that I've only worked at tertiary care cancer centers. It's really not that hard to get enrolled if you meet criteria. I believe the stories we read of access challenges are largely a vocal minority with challenging circumstances or a misunderstanding of treatment options.
No problem. I appreciate the discussion, it's good for me (and medicine in general) to be challenged on held beliefs as things tend to devolve insidiously in this field.
> But I'd like to hear your thoughts on the broader argument of being more aggressive with trials in general. What sticks with me each time this argument comes up, regardless of the particular situation, is this idea that despite some mechanisms for accelerated approvals, we are still far slower than we could be, if we take into account the number of people saved by bringing therapies sooner.
Everything in medicine is trade-off. On the extremes we can practice with no regulation and have immediate access to treatments without evidence accepting that many patients will be harmed as many new treatments are inferior or require phase IIIs on the other end and minimize harms but accept that delayed care will itself cause harm.
Current practice is somewhere in the middle, depending on various factors like efficacy, risks/harms, and alternatives many treatments enter practice after phase I/II or used off-label for close indications.
I like where we're currently at for oncology and don't think we need to change much in the process. The bigger hurdle is funneling those R&D $ into high yield research and perhaps making the cost of trials easier (e.g. research alliances, IT infrastructure to simplify multi-center studies and patient recruitment, ?active government involvement).
There's always fine tuning of that balance that can be done and some cases will prove things wrong on either side of the argument but generally speaking I think we're close to where we need to be. Definitely better than when we didn't have the current approval process.
> It's the counterfactual that makes the argument, the people who do not receive treatment due to delay seems to vastly outnumber the people harmed by experimental treatments.
I don't think this is true and I have not seen evidence to support this claim. There is ample evidence of failed treatment options or treatment causing more harm than good. An example I'm well-versed in is HIPEC for advanced ovarian/peritoneal cancers (we've been doing this for years and it turns out it doesn't do much other than excessive morbidity) or Y-90 for HCC/colorectal metastases to the liver (first trials negative and we recently found out "oops we've been underdosing this and measuring non-target dosing to the lungs incorrectly") both of which are for palliative patients with no good alternatives.
Going back to osimertinib as the example, the main criticism of earlier TKIs (same class of drug, and even osimertinib for that matter) was that the promise of limited data (progression free survival rather than overall) led some patients to get TKI therapy rather than platinum based chemo which was standard of care and has proven OS benefit. Except when the OS data came out it was an "oops, OS didn't pan out like PFS" and people were harmed.
That these happen in the current system strongly suggest patients have access to experimental therapies and that we're not being overly stringent, or this data wouldn't exist.
I would also say that a large proportion of the patients I've interacted with that have disseminated disease are on some trial for experimental therapy with the caveat that I've only worked at tertiary care cancer centers. It's really not that hard to get enrolled if you meet criteria. I believe the stories we read of access challenges are largely a vocal minority with challenging circumstances or a misunderstanding of treatment options.