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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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June 16, 2014

A "Right to Try" Debate

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Posted by Derek

For those interested in the "Right to Try" debate, BioCentury TV has a program that includes both the pro and the con sides of the debate. Worth a look to see how sharply opinions divide on this issue - and I don't see them converging any time soon.

Comments (22) + TrackBacks (0) | Category: Clinical Trials | Drug Development


COMMENTS

1. Anonymous on June 16, 2014 7:32 AM writes...

Why is there even a debate on this: As long as patients (properly informed of the risks) and companies both agree to go ahead with this, then what business is it of anyone else to make this decision for them? It's no different from the debate on gay marriage - too many people trying to enforce their own views on others, on matters that don't concern them.

Live and let live, is what I say.

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2. John on June 16, 2014 10:11 AM writes...

Phase 1 drug is just as dirty as a rat.

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3. Anonymous on June 16, 2014 11:26 AM writes...

>then what business is it of anyone else to make this decision for them?

The same business of the FDA and the doctors that give prescriptions for drugs in general.

There's already complaints about how some people force (or constantly switch) their doctors to go for expensive scans and to prescribe SOMETHING regardless of the doctors opinion.

And this is without concerning the safety of the untested drugs and possible exploitation/abuse from shady drug companies.

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4. Anonymous on June 16, 2014 11:27 AM writes...

@ #1,

Many problems would be solved if we had perfectly informed customers and unwaveringly honest businesses.

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5. hypnos on June 16, 2014 12:15 PM writes...

There may certainly be cases where access to a (potentially) life-saving drug is not easily possible for a patient (e.g. because he or she does not fit into the pre-defined inclusion criteria). In such cases, a program like this might help - but I guess that there are only few of such cases and there is no reason not to put this under the supervision and monitoring of some independent ethics & experts committee.

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6. dearieme on June 16, 2014 12:21 PM writes...

The lawyers must be salivating.

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7. Anchor on June 16, 2014 12:23 PM writes...

@1, Not a good ides. This will open up the flood gate for the so called approval of "garage" drugs! The American family members will still have a right to sue, after agreeing to all and then die! A policy such as the one you are proposing will make trial lawyers day.

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8. Anonymous on June 16, 2014 12:52 PM writes...

@3,4,7: And why is it any of your business, either? Are you dying? Why should you (or I) have the right to choose whether those who are dying have the right to try? See the hypocrisy?

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9. david e. young md on June 16, 2014 1:39 PM writes...

#5 Are there cases where a patient could be aided by an investigational drug but could not get the drug because they don't meet the inclusion criteria? Yes, it happens all the time. It would be this cohort of patients, who can't get the investigational drug for their deadly glioblastoma because they are on Lupron for their well-controlled prostate cancer (for example) where expanded access programs would help. Happens all the time. Those patient could really use access.

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10. david e young md on June 16, 2014 1:47 PM writes...

Although I would like programs for expanded access for investigational drugs, I can see the standpoint of the drug sponsor, the manufacturer. First of all, they may have a limited supply of their investigational drug and must pool their resources in getting the drug through clincal studies and the registration trials. Second, having an expanded access program requires tons of paper work. Third, if the investigational drug is made access to really sick patients off trial, there is the risk of really bad sounding side effects being added to the paper insert list of side effects. Remember, everthing bad that happens to a patient is listed as a side effect, without much regard as to the cause. And if two patient die of brain infection only because they were super sick when they got the investigational drug, the studies could be put on hold by the FDA.... which is a nightmare to the sponsor. Fourth, even letting some super elite university specialist get the drug on companssionate use requires by law that everyone else, including the lone oncologist in rural Montana to have a right to get the drug on compassionate care. I can certainly understand a company's reluctance to offer their early stage drug outside of a study.

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11. aa3 on June 16, 2014 3:02 PM writes...

Even in an extreme example where a revolutionary treatment was curing people in early stage trials... if I was the owner of the company behind the treatment, I would not open it up for compassionate care. It falls into the 'no good deed goes unpunished' category. It is just begging for lawsuits and as #10 said, FDA halt on the official studies when very weak people die of one thing or another.

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12. Dr. Mark on June 16, 2014 3:45 PM writes...

It is not possible to be informed about a drug until the trials have been done. Lots of times there are toxicities that show up that are unanticipated. Typically, phase I trials establish a reasonably not too toxic dose for the presumptive medication. Before those trials are done no one knows what the dose should be. Compounds then undergo further testing to see if they are of any use. The vast majority of compounds turn out to be ineffectual. Even drugs that complete this gauntlet can turn out to have unacceptable toxicity when they are given to enough people; remember the NSAID's that turned out to have fatal cardiac toxicity.
Very, very rarely something shows a lot of promise in early trials. Imatinib had such an exceptional history, but it must be remembered that big Pharma dragged its heels because the CML market appeared too small.
A new drug, ceritinib, which was designed after a very sophisticated analysis of the target has apparently scored a home run in the phase I trials, and is headed for approval in record time.
In the past, the chances of a incompletely tested drug being useful was very tiny, and it would have been a cruel hoax to allow desperate people to use it. However, science is advancing, and the ceritinib design paradigm may really change the balance and resolve this problem.

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13. Anonymous on June 16, 2014 4:43 PM writes...

To say that "It is not possible to be informed about a drug until the trials have been done" is rubbish. One can easily measure the risk based on what *is* known and say, for example, "there is maybe no more than 5% chance the drug has any positive effect, and maybe over 50% chance that it has some negative side effect, which may be very serious and may even accelerate terminal illness. Then let people decide if they are happy to take that chance, while giving up any right to sue. If I was terminally ill I may well consider it. But my point is that nobody here who is not terminally ill has the right to decide for those who are, because an individual's risk appetite will be so different in such circumstances.

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14. Bagnar on June 17, 2014 2:21 AM writes...

#10 Aka "david e young md"

"Third, if the investigational drug is made access to really sick patients off trial, there is the risk of really bad sounding side effects being added to the paper insert list of side effects. Remember, everthing bad that happens to a patient is listed as a side effect, without much regard as to the cause. And if two patient die of brain infection only because they were super sick when they got the investigational drug, the studies could be put on hold by the FDA.... which is a nightmare to the sponsor. "

I though, and I may be wrong, that these people, as volunteers, were not part of the trial program. Are their data / feedback, recorded and are they taking part of the FDA approvement process ?
If yes, you're absolutely high risk took by the company. If not... I let you guess what could happened.

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15. Anonymous on June 17, 2014 6:37 AM writes...

Looks like most of the people who comment here are drug discoverers rather than developers.

In my view there are enough ways to get to promising therapies before they are approved. I also agree with the statement in the video that RCTs has a design from the 20th century. We are being ruled by rigorous statistics. On the flip side, we do know about wonderful "proven" effects of homeopathic medicine. The mind can be so powerful in healing

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16. david e young md on June 17, 2014 10:47 AM writes...

#14 When a patient is able to receive an investational drug as part of an expanded access program or compassionate use program, the side effects experienced by the patient are still reported to the FDA. In fact, any negative thing that happens to the patient is reported to the FDA as a possible side effect of the drug. If a patient receiving an immunsuppressant drug as part of compassionate use and that patient dies of Progressive Multifocal Leukoencephalopathy while on (or soon after) the course of the investigational drug, that serious adverse effect is reported to the FDA. As a consequence the registration trial may be stopped temporarily or the drug may get a black box warning because of this experiencd outside of the registration trial.... even if there is reason to believe that the patient receiving the drug by compassionate care use was much more ill (previously immunocompromized) than patients allowed in the registration study. This is among the pitfalls of allowing an investigational drug available outside of the registration study (or phase II studies for that matter). Reported serious adverse effects can have a detrimental effect on the developement of the drug, even though the serious events happened in people much more prone to them (or not due to the drug iteself).

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17. asb on June 18, 2014 4:11 PM writes...

I'm not a scientist, but as the relative of someone with stage 4 lung cancer, I think the access criteria could definitely stand to be loosened. I don't quite understand the purpose of control groups in clinical trials for terminal patients. I'm pretty sure that the results of standard-of-care treatment, i.e. death, are quite well documented by now.

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18. david young md on June 19, 2014 10:44 AM writes...

#17 asb Not so sure what you mean by that. Everyone dies eventually, so if ever dying is the means for comparing treatment, then nothing would be found to be better than anything else. If the average time death after treatment "A" is 8 months and the average time of death after treatment "B" is 24 months, I think that everyone would agree that treatment "B" is superior to treatment "A" even though everyone ultimately dies of the disease. For registration studies you must have a comparetor "standard of care arm" so that you can tell if the investigational arm is in fact better than what is currently available. All the same, an investigational drug would be considered highly promising if it was able to make cancer regress (in the setting of treating cancer patients, for instance) without much adverse effects. But yes, for registration, you need a control arm. How else are you going to tell if the experimental treatment is superior?

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19. asb on June 19, 2014 5:19 PM writes...

18: I mean I think people have a pretty clear idea of how much time is given by standard treatment. Maybe I am overestimating the amount of knowledge already available to researchers.

Let's say there are several clinical trials that are all attacking a certain kind of lung cancer. One is using pill a, one is using pill b, one pill c. Do studies a to c all need their own unique control group or is one enough for the whole group?

Don't researchers collect statistics on cancer patients whether they participate in trials or not? Can't they use the set of people (ie most patients) not participating in trials as the de facto control group? Is it to weed out environmental factors (as in this test was performed in San Diego at the time of an alien invasion so the patients turning purple was due to outside interference)?

Obviously I'm not a scientist so I should probably stop talking. I understand the purpose of a control group. I just think perhaps that data is available elsewhere and patients who volunteer for trials in order to get access to new treatments should be given that access.

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20. Anonymous on June 20, 2014 12:41 PM writes...

13- Yes, and that is what clinical trials are! Which is exactly what hasn't been done for these drugs.

asb- that assumes that your testing population has the same biases those of the other control groups or no bias in terms of comparing it to the population.

Generally, I'd not assume the people that would participation in testing are the same as those that do not. Though reusing them for separate tests of the same or similar drugs is probably not unheard of.

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21. david young md on June 23, 2014 12:10 PM writes...

#19 asb

"I mean I think people have a pretty clear idea of how much time is given by standard treatment"

No they don't because it depends greatly on how ill the cohort of patient are, and that cohort changes everytime.

You think that every metastatic breast cancer patient has so many months to live without treatment and you can put a number on it. Instead, it depends upon many factors; burden of disease, pattern of metastases, presence or absences of HER2 overexpression, hormone receptors and probably another 4 or 5 molecular characteristics that we don't know about. A particular cohort of patients on study may have a bad form of cancer or not so bad, so you can't say ahead of time that they would live 6 months or 6 years on the average. That is why you must have a control arm (who get the standard of care treatment) and the experimental arm and the patients are randomized to one or the other arm. You can't get around it.

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22. Avoir Skin on July 16, 2014 5:55 PM writes...

I enjoy reading a post that can make people think.
Also, thanks for allowing for me to comment!

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