Right To Try law has a big loophole that’s an opening for bad actors

Young man rides piggyback on an old man

Young man rides piggyback on an old manThere appears to be a big, risky loophole in the relatively new national Right To Try law.

Some folks apparently anticipated this problem long ago, but I think most of us weren’t aware of it. Update: More specifically, some law and policy experts were writing about this and other potential loopholes in 2018. I recommend this piece from Beth Roxland and Elisa A. Hurley on the The PRIM&R blog.

What’s the deal?

It seems to be a case of what I would call piggybacking that could be a big opening for what the FDA has labelled “bad actors” including certain unproven stem cell clinics.

Keep in mind that the apparent core safety mechanism of this national Right to Try law is the requirement for an existing FDA-cleared investigational new drug (IND) and Phase I data.

That means that the national Right to Try law includes a strict requirement for the treating physician or team to have such a cleared IND and Phase I trial data, right?

Actually, it doesn’t.

The reality of this law instead seems to be that the treating physicians doing a RTT program actually do not need a cleared IND or Phase I data. It is the drug that they propose to use that has to have a cleared IND and have Phase I data.

This isn’t a trivial distinction.

It means that while one specific research team may have done all the work to get the cleared IND and run a Phase I trial, someone entirely different, perhaps in some cases even an individual doctor with no experience in using the investigational drug or even in the general area of the clinical research or the type of medicine needed for the specific patients, could then in theory use the same drug themselves on patients in a RTT context.

So, for example, if a Chicago research team has developed “Drug X” (a kind of autologous stem cells, let’s say) that is part of an IND cleared program and has Phase I data, then an entirely different group that we’ll call the New York team may be eligible for RTT use of Drug X.

And that New York team or doctor could be just about anybody.

As long as the New York doctor is licensed and in good standing in their state, from a national RTT perspective it doesn’t seem to matter who they are, their training, or anything else. Apparently the national RTT law defines eligible patients and eligible drugs, but has little to say about what it means to be an eligible doctor or research program. (State RTT laws are somewhat different.)

This is the big risky loophole in the law, perhaps an intentional one.

I asked FDA and biologics regulatory oversight expert Professor Patti Zettler from The Ohio State University Moritz College of Law for her thoughts on this potential loophole and gave her the hypothetical example of an investigational bone marrow drug product being used in RTT:

“In general, it is correct that, under the federal law, to be eligible for “right to try,” an investigational drug must be one for which a Phase 1 trial is complete and one that is subject to an active IND and is actively under development. The law does not say that the person or entity providing the drug for right to try must be the same as the person or entity holding the IND or conducting the clinical trials.
You raise an interesting question as to whether this creates a loophole of sorts, where someone not involved with the IND could manufacture the “same” drug—and escape the IND requirement in that way. With a small molecule drug, I think the answer should clearly be “no.” If manufacturer A produces Drug A, and only manufacturer A’s drug A is subject to its IND—that is the only drug eligible for “right to try.” If manufacturer B makes a separate version of Drug A, that would be a separate drug, not subject to manufacturer A’s IND and not eligible for “right to try” (until and unless it satisfied the criteria in the statute). In other words, the “right to try” law, as I read it, is not permission for manufacturers to make and distribute copies of products their competitors are researching, simply because their competitor has an IND. With something like a bone marrow derived autologous product, perhaps the question is a bit trickier, because manufacturing isn’t the same as with traditional small molecule drugs. But I think the same logic should apply—that is, only those products covered by the IND would be eligible for “right to try.”
Of course, only time will tell as to whether FDA would enforce in such scenarios, but it seems to me that it could.”

So there is an opening here for RTT programs that are often not in patients’ best interests.

It also perhaps means that, for instance, our hypothetical New York doctor could administer what they see as their version of the biological Drug X to patients under the auspices of national RTT even though it’s possible it might not be exactly the same thing as what the Chicago team has in their IND-cleared program. But let’s say the New York doctor calls it the same drug. Would the FDA view that as acceptable? Like Zettler, I doubt it, but even if we’re right then what happens?  Can the agency try to pull things back after a specific RTT program already got going? Even if it could do that, would it? Would politics come into play?

Also, who decides if it is the “same drug”? The doctor proposing the RTT use of it? The FDA? Remember that FDA doesn’t necessarily get much of a chance to vet RTT arrangements.

One can also imagine some unproven stem cell clinic doctors, maybe even some who have had problems with the FDA and that again the FDA calls “bad actors” trying to take advantage of this loophole to piggyback on a different firm or university’s IND/Phase I data to claim RTT-based use of what they call “the same drug” in their for-profit clinic. That can’t be good for patients. To be clear I’m not questioning patient autonomy when facing a fatal illness, but rather I’m concerned they will be used for profit in some cases. Not all of the risk from this RTT law comes from “bad actors”. Some others may accidentally put patients at risk via the law’s loophole.

Some of this is likely already happening right now. Check out this new piece in Cell Stem Cell by Doug Sipp, Leigh Turner, and John Rasko, which documents some concerning instances of marketing related to RTT already.

The financial side of this is also potentially problematic. While in a RTT context legally a firm can only charge patients the cost of the drug product (again in our hypothetical scenario we’re using the example of some experimental stem cell product), it seems perhaps they can try to add on other costs too. For example, while a patient may “only” pay $3,000 for the investigational stem cells in such a RTT scenario, the clinic could require another $13,500 in supposed essential costs to boost profits.

Overall, I believe the national RTT law has the potential to harm many patients, perhaps far more than it might help. Patients with fatal illnesses such as ALS and Huntington’s need options. The FDA’s current expanded access/compassionate use program isn’t perfect, but it has improved and it gives patients options. If some folks still feel we need a mechanism beyond compassionate use, I don’t see this national RTT law as being the wise option in part because of the big loophole.

14 Comments

  1. In your sensario you write: “But let’s say the New York doctor calls it the same drug.” Well, that’s called fraud. The FTC would be very interested in that kind on false advertisement with perhaps bigger teeth than the FDA !

    • It seems some firms (without INDs) that are already pursuing Right to Try-based stem cell interventions are led to believe that if they follow the same protocol as a totally different group that has an IND/Phase I data, that they can call it “the same drug” and have RTT eligibility. So they are going forward based on that assumption. It seems to me to be at best a huge gamble and in my opinion it’s not the same drug. It would sure help if FDA could clarify how same drug is supposed to be defined.

      As to the FTC, if the firm in question is not marketing the RTT Intervention then the FTC wouldn’t do anything. It’s unclear how the FDA will deal with this kind of thing and when.

  2. Paul , why are you ignoring Mesoblast s achievements is it because you don’t believe in what they are doing …Thanks Vin

  3. Dear Dr. Knoepfler,

    I’m curious to know your opinion on patients paying for legitimate RTT programs. You seem to be against patients paying for legitimate, FDA-approved, clinical trials so are you also against patients paying for RTT?

    • Hi StemCellLady,
      If a RTT program is legit and the treating physician has done a Phase I clinical trial themselves already and has a cleared IND, given the urgent circumstances of a fatal illness, I think there may be circumstances where it is reasonable for patients to pay just “at-cost” for something if they are properly consented.

      The same goes for the FDA’s expanded access/compassionate use program. I don’t know off hand the charging rules for compassionate use though.

      However, there are risks here too and sometimes I think it could go wrong. I’d recommend patients also discuss this kind of thing and the potential risks/benefits with their primary care doctors too, who to me seem to be very common sense oriented and logical.

      Also, depending on the cost some very sick people may be excluded and is that fair? In other cases, patients may be given a false sense of the chance of benefit or even be convinced by the sponsors that they may be cured.

      As to more standard, legit FDA-cleared clinical trials outside the scope of RTT, yes I’m generally not a fan of the idea of charging patients just to enroll.

      • I guess I’m confused. So you are OK with patients paying for (all legitimate) expanded access and RTT but not in a clinical trial? The expanded access is a clinical trial with an n=1. In EA and RTT there is probably more in question with regards to whether the drug is safe or has any effect. Passing a phase I trial means that the drug is safe for a particular condition. EA and RTT can be used (sponsor provided) in populations where the drug has not been tested so the patient needs to be properly informed and make that decision. How is this different than patients enrolling in clinical trials? You say that clinical trial patients shouldn’t pay for something that might not even be safe but shouldn’t the same argument hold true for EA and RTT?

        Note: Under FDA’s expanded access program, with FDA authorization, a sponsor can charge a patient for direct drug manufacturing costs, monitoring the protocol, complying with IND reporting requirements and other administrative costs directly associated with EA. Without authorization, they can recover the costs of administration, followup testing, site/hospital fees etc.

        • It’s not that simple. Note various potential caveats and risks I mentioned in the comment (and there are even more I could list) and there are other risks too so it’s not black and white that I’m “OK” with it. It’s very gray and hard to generalize. It makes sense to me that patients with fatal illnesses should be able to, if they and their physician think it’s reasonable, to try things that are higher risk than potential participants in a “regular” clinical trial, and if they can get the sponsor to be on board. But the charging component in either case really makes it all a lot more complicated.
          What’s your view?

      • Primary care physician know very little about this area of treatment. Asking for their input adds very little.

  4. I wholeheartedly agree with your statement that “It’s very gray and hard to generalize”.
    But unlike you, I would stop there.

  5. Worth noting that Sec. 561B(b) provides remedies to try and deal with some of these loopholes you’ve identified. I don’t doubt bad actors will try to bend this law using the broadest interpretation possible, but I can think of several strong lawsuits that could be brought to cut off abusive use of this law. Worth noting that consumer protection attorneys like myself are keeping a close eye on this.

  6. Also, IRB review or approval is not required for Individual Right to Try Act requests. Physicians in practice are usually not aware of the federal regulations governing research, and most physicians will not have received training in clinical research or human subjects protections. Further, given few restrictions on these procedures, and an incentive to make money because the patient can be required to pay for the unproven treatment, unscrupulous physicians, such as Farid Fata, can move-in using this law. Mr. Fata is the Michigan oncologist who gave $35 million in needless chemotherapy to patients — some of whom didn’t even have cancer. “Physicians are more likely to perform unnecessary procedures when they profit from them,” and “20.6% of overall medical care was unnecessary” (Lyu et al, 2017, PloSOne, 12(9): e0181970). Unregulated healthcare, especially when monetized, is an oxymoron.

Leave a Reply