
Thoughts on AbbVie’s Rova-T Implosion - aaavl2821
http://blogs.sciencemag.org/pipeline/archives/2018/06/05/more-thoughts-on-abbvies-rova-t-implosion
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djrogers
Most (all?) current right to try legislation involves drugs that have already
passed safety protocols, but are not approved for treatment of a specific
condition, or drugs currently approved in other countries for treatments.

To deny a terminally ill patient a drug that may save her life and is unlikely
to cause further harm is the height of regulatory hubris.

~~~
olliej
This is literally exactly the scenario you're talking about: The drug looked
like it would work, so much so that someone decides to spend $6 billion to buy
it before it completed stage 3 trials.

Now it turns out that not only does it not work, it also actively made things
_worse_. So your "terminally ill patient" and the "drug that may save her
life" turns out not to be "unlikely to cause further harm".

The existing regulatory regimes allow for the patient to end up in a trial for
a drug like this, but the "right to try" law now means the subject can be 1)
charged for it and 2) not provide useful information for other patients
because they're no longer in a blinded trial environment.

~~~
djrogers
Ending up in a trial != getting the treatment, and fewer than 3 percent of
terminally ill patients gain access to investigational treatments through
clinical trials.

Current 'compassionate use' exceptions are even worse - only 1,200 of those
are granted each year to the lucky few, out of hundreds of thousands of people
who could use them.

Also, don't you think it's rather hypocritical to imply that being in a trial
(if you win that lottery) is safe, while getting the drugs unfer RTT is not?

Yes, there will no doubt be failures, but to deny a terminally ill patient the
right to choose what to do with their own body seems rather crazy to me.

~~~
olliej
No i don't think it's hypocritical.

Right to try laws allow companies to monetise desperate terminally ill
patients. That's been shown repeatedly throughout history (and these days in
the 'supplements' industry) to result in abuse of dying patients. And you get
things like [https://www.statnews.com/2017/11/21/herpes-vaccine-hotel-
roo...](https://www.statnews.com/2017/11/21/herpes-vaccine-hotel-rooms/) which
was clearly a great plan - and yeah that's not "terminal", but the exact same
kind of thing can happen for terminal diseases as well.

The trial methodology removes the financial incentive, so that now you can't
just take all of a dying persons money.

By keeping the treatment in the trial model you also mean that we get data
that can actually help -- maybe find out that the drug does not in fact work,
or maybe finding out that it does! A patient who is not being treated under
trial conditions is much less useful as a data point (if at all) because the
placebo effect, and a bunch of other related ones, have repeatedly been found
to lead to incorrect feedback - the person says that the drug makes them more
comfortable, even though they didn't live any longer, is that because it
actually made them feel better? Or was it placebo? Or was it a desire to be
"helpful"? If you use them as a data point you may end up with a drug that
doesn't actually help, and that drug gets sold. for money. to people who it
doesn't help. Cool.

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mercurialshark
As a counterpoint: New Immunotherapy Treatment Removes All Tumors In Woman
With Advanced Metastatic Breast Cancer

[https://www.cancer.gov/news-events/press-
releases/2018/immun...](https://www.cancer.gov/news-events/press-
releases/2018/immunotherapy-targets-breast-cancer-case-report)

[https://clinicaltrials.gov/ct2/show/NCT01174121](https://clinicaltrials.gov/ct2/show/NCT01174121)

[https://www.forbes.com/sites/victoriaforster/2018/06/04/new-...](https://www.forbes.com/sites/victoriaforster/2018/06/04/new-
immunotherapy-treatment-removes-all-tumors-in-woman-with-advanced-metastatic-
breast-cancer/#963363100550)

[https://www.cbsnews.com/news/immunotherapy-treatment-
saves-l...](https://www.cbsnews.com/news/immunotherapy-treatment-saves-life-
of-woman-with-late-stage-breast-cancer/)

~~~
dwyerm
How is this different than the existing Compassionate Use [1], program? Under
this program my dad had access to try treatments for his terminal cancer. What
does Right To Try offer over that?

[1]
[https://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAcc...](https://www.fda.gov/NewsEvents/PublicHealthFocus/ExpandedAccessCompassionateUse/default.htm)

~~~
nordsieck
Having just skimmed the text, it seems like the difference is similar to the
difference between "shall issue" and "may issue".

Fundamentally the FDA is very against right to try because they believe,
correctly, that it reduces the incentive for patients to participate in
medical trials - why risk being in the control group if you don't have to? My
(perhaps flawed) understanding is that the FDA doesn't not approve
Compassionate Use very often for this reason, although they probably use
safety as the official excuse.

~~~
aaavl2821
The null hypothesis in clinical studies is that the investigational drug
doesnt work. Most of the time it doesnt and patients are better off getting
standard of care

There are also ethics guidelines that deal with control group selection. If an
effective approved drug exists, usually that has to be the control arm, not a
placebo. So a patient will get a drug that works in the control arm, though
maybe not in the active arm

~~~
nordsieck
> Most of the time it doesnt and patients are better off getting standard of
> care

The context for "right to try" is a person with a terminal condition that does
not respond to any conventional therapies. In essence, the choice is between
experimental treatments and hospice.

> If an effective approved drug exists, usually that has to be the control
> arm, not a placebo.

There will always be a placebo in a stage 3 trial.

~~~
aaavl2821
There is not always a placebo in Phase 3 studies. You can have an active
control. Here's an example [0]: active arm is upadacitinib, control is
methotrexate (the standard of care)

FDA guidelines are you need "at least two adequate and well-controlled
studies, each convincing on its own, to establish effectiveness" [1]. Well
controlled can be placebo controlled or active control

[0]: [https://www.prnewswire.com/news-releases/upadacitinib-
monoth...](https://www.prnewswire.com/news-releases/upadacitinib-monotherapy-
meets-all-primary-and-ranked-secondary-endpoints-versus-methotrexate-in-a-
phase-3-study-in-rheumatoid-arthritis-300659605.html)

[1]:
[https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegula...](https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm072008.pdf)

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Shivetya
Can we please change the title to match the article instead of being
sensationalized/ politicized ?

~~~
asdsa5325
^ This.

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aaavl2821
Another pretty harmful potential downside of "right to try" is that while FDA
may no longer hold as much sway, payers will still be gatekeepers. Payers will
decide what to pay based on evidence and will not pay for drugs with little
evidence to support their effectiveness. So patients will be stuck with the
costs, and end up paying more than they do now

There is precedent for this in the world of molecular diagnostics. Certain
tests can be marketed without FDA approval. However few companies are
successful because insurers wont pay and patients wont pay enough

------
oh_sigh
Derek's argument seems to be that some drugs may actually harm patients, and
so Right to Try is bad.

Isn't that known, and just something terminal patients need to balance with
their doctors? If I had 6 months to live, I would probably roll the dice for a
cure even if 50% of the time the drug would actually only give me 3 months to
live.

I doubt anyone believes that trying experimental drugs can only help, and
never hurt the patient. If that was the case we'd have been allowing
experimental drug usage for a long time.

~~~
jcranmer
The problem with right-to-try is that it's framed as "Big Bad Pharma (and/or
FDA's onerous regulations) is preventing these life-saving cures from getting
to people, we need to get them sooner." Yet the experimental evidence is most
drug candidates fail because _they don 't work._ Even the big, expensive phase
III trials have about a 50% failure rate. If you're pushing for access much
earlier (concurrent with phase I), that means you're pushing for access before
there's data on how lethal the drug is.

Derek's big concern with right-to-try is that it's basically a way to advocate
for taking the science out of drug approval. Data outside of a well-controlled
study is hard to use, but the public _will_ lobby for it to be used. And the
concern isn't idle: when the FDA's response to the bill was "we're going to
look into how to do this safely," the reply form a key Senator was "no, no,
no, you don't understand, we're trying to tell you to get out of the way." The
end goal would be to eliminate the FDA as useless bureaucracy, but we already
have an example of what unregulated drug industry looks like: it's called the
health supplements industry, which is so sleazy that many companies don't even
bother to include the active ingredients they claim to include.

~~~
olliej
Don't forget Thalidomide, etc.

People seem to forget that there was a time where the FDA and trials didn't
exist. And that the reason the FDA has to exist is because otherwise you get
very expensive "drugs" that frequent, at best, do nothing, and oftentimes do
harm.

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masterleep
The idea that bureaucrats and scientists should be able to decide what
experiments a terminally ill patient should be allowed to participate in is a
deeply evil one.

~~~
eesmith
"Deeply evil"? Is this based on ideological considerations which reject any
sort of government oversight?

We have experience of what sort of quack "medicine" appears when unscrupulous
people take advantage of the hopes of the terminally ill for personal gain.

Is that what you want us to return to? Or do you have a way to prevent it?

~~~
masterleep
If I am dying, what right have you to tell me what experimental treatment I
can take or not, if I otherwise have no hope to live? You would condemn me to
no hope at all in order to save me from what you consider to be unproven or
possible quackery.

~~~
eesmith
We are all dying. We are all condemned. So if you're going to use such
emotional words, at least ground it in real-world examples.

Here's a real-world example - [https://www.livescience.com/4040-dying-
desperate-lure-quack-...](https://www.livescience.com/4040-dying-desperate-
lure-quack-medical-clinics.html) .

People in the US in the last months of their lives, in desperation, go to
Mexico for "treatment" by methods which have never ever worked.

> One hospital we visited offered homeopathic treatments. (Homeopathy is a
> form of quack medicine essentially based on the mystical principle of "like
> cures like.")

> Another, respectable-looking hospital offered such "alternative" treatments
> for cancer as shark cartilage, mega-doses of vitamins, and "prayer therapy."
> The hospital also offered Laetrile, a notorious cancer treatment discredited
> by repeated scientific studies.

> ... Donsbach's clinic had a reputation for providing questionable medical
> procedures, including "ultraviolet blood purification," colonics (a
> potentially dangerous colon-irrigation therapy), and the use of microwaves
> to "heat" cancer cells.

This is what you want, everywhere, yes?

~~~
masterleep
I believe in the right of individual self determination in matters of life and
death, even to the point of foolishness, yes.

~~~
eesmith
It would have been easier if you had said that my first statement was
essentially correct - your belief is based on an ideological consideration
which rejects government oversight on the broad topic of "life and death."

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2RTZZSro
In some sense we are all terminally ill so I'm interested to see how far they
will push the definition of a terminal illness.

