Last week, Pres. Trump signed the federal right to try law. So what happens next? Meaning, who is it going to affect and how big of a difference is it going to make in the lives of the terminally ill and those without any other therapeutic option.
Why a federal law was needed?
As most of you know, a majority of states have already passed a right to try law. The problem with just having the law on a state level is that the state laws were inconsistent with federal law, in the same way as state medical marijuana laws are inconsistent with the federal DEA drug laws.
But the inconsistency was much more impactful in the prescription drug context, because as I and others in the field have said, the drug companies wouldn’t want to anger the FDA by providing their investigational drugs in violation of federal law, even it was supposedly legal under a state’s law.
A good rule to follow for a drug company seeking FDA approval is not to piss-off the agency which has all but unreviewable power to grant, deny or delay marketing approval. A federal right to try law technically obviates the inconsistency. So for drug companies which wanted to provide investigational drugs beyond clinical trials and expanded access, an important impediment has been removed, in theory at least. (And as discussed later, it’s not clear to me why any drug company wants this law or will use it.)
What are the requirements?
Patient eligibility: the law applies to a person with a “life-threatening disease or condition,” which the FDA defines narrowly as “where the likelihood of death is high unless the course of the disease is interrupted and “where the end point of clinical trial analysis is survival.” (21 CFR 312.82). It is interesting to note that this regulation also defines “severely debilitating” as a disease or condition that causes major irreversible morbidity.” But the law doesn’t apply to people with conditions like MS or any other severely debilitating diseases or conditions, since the likely result of MS and other seriously debilitating diseases is not death, and the purpose or clinical trial analysis is not survival in these types of clinical trials.
The bottom line is that the law does really only apply to patients who have a terminal illness and who have no other treatment options. Think metastatic cancer and maybe ALS (and I’m sure there are other diseases, but I’ll leave that to the docs to figure that out.)
The law also prohibits the doc certifying the terminal condition from receiving direct compensation for the drug manufacturer. And of course, proper informed consent is required, but that always a requirement with investigational drugs.
Requirements for the drug
Most importantly: the drug has to have gone through an FDA approved Phase I clinical trial. Phase 1 is usually a small toxicity study, the goal of which is to make sure that the drug isn’t too toxic to administer to patients at the expected therapeutic dosage.
Phase 1 studies do not have to show efficacy; however, a drug which shows zero efficacy might not create much enthusiasm from the sponsoring drug company to justify the cost of further study. And I would think that most people might want to see at least some benefit, however small, from a study, or at least some anecdotal evidence of some positive result. My sense is that many drugs which have passed through phase 1 can show at least some marginal improvement in some subjects. This is the case despite the fact that the overwhelming majority of post phase 1 drugs don’t get approved. (And there are a lot of reasons for that, including the obvious that the drug doesn’t work, or doesn’t work in a high enough percentage of subjects).
The post phase 1 drug must also be in active development and not be on a clinical hold.
Requirements of the drug sponsor/manufacturer
There are three requirements imposed on the sponsor, two are simple: the drugs have to be properly labeled as investigational, which is easy because the drug was already given in a phase 1 study and the drug label had already been approved by the FDA. (A small change in the label might be required.)
Second, the sponsor can’t promote the safety or efficacy of the drug, but a sponsor is not allowed to do that in clinical trials either. So the sponsor doesn’t have to do anything different from its actions (non-actions) in the clinical trial.
Third, the sponsor at most can recover the direct costs of the drug provided to the patient, but that’s a narrow and parsimonious amount of money. I read the statute as not requiring an accountant’s certified statement supporting the cost recovery which is the case when a sponsor wants to cost recover for patients in clinical trials. The bad news (for the drug company) is that the direct costs for each patient is likely to be an insignificant number as it doesn’t include the drug’s development costs. So I don’t see many drug companies charging for the investigational drug.
Protections for the sponsor/prescriber
If the sponsor and prescriber follows the law, they can’t be sued for simple negligence, but they can be sued for alleged reckless or willful misconduct, gross negligence or an intentional tort under state law. Practically speaking, that’s not all that much protection since it’s easy to allege facts which show more than simple negligence. But it’s something.
Reporting results of the right to try use
The manufacturer or sponsor has to provide an annual summary of the use and serious adverse events. (Adverse events don’t require a causal connection to the drug, just a temporal association.)
Can the FDA use the serious adverse in evaluating the sponsor’s new drug application?
Yes, but only if the FDA determines that the use of the data is critical in determining the safety of the drug. That’s pretty broad. I would expect that if the drug is producing many serious adverse events, beyond what was reported in the results of the regular clinical trials, these data will be carefully looked at by the FDA.
The good news for sponsors
The statute specifically states that drug manufacturers do not have to provide investigational drugs pursuant to the law, and can’t be liable for not doing so.
Why is that good news for them?
I am hard pressed to think why any manufacturer involved in clinical trials would agree to provide its drug under this law. All I see is downside. The patients likely to want its drug are probably a lot sicker than the subjects it selected via entry criteria to get the drug on the study. The sicker the patient, the more serious adverse events which may or may not have been caused by the study drug, but as indicated, adverse events aren’t about causation, just a temporal association. Drug sponsors try to stack the deck in their favor by treating the healthiest patients than can with the condition. Why stack the deck the other way?
I can only think of two circumstances where that would make sense.
First, the results of the phase 1 study are so spectacular and the company lacks the funds to do further clinical studies. It might make sense to push a lot of people onto the treatment to amass more spectacular data.
Second, a sponsor/manufacturer is a physician and the business model involves providing an investigational drug to patients. But that’s a very rare model in the U.S.
The bottom line is that I don’t think many drug companies will voluntarily use this law. Frankly, if I was asked to advise a company about it, I’d tell them not to do so other than the two above circumstances because I just see downside. I know that sounds harsh, but the main job of a drug company developing a new drug is getting it approved. Anything that helps that process should be pursued. Anything that doesn’t, could hurt, or distracts from approval shouldn’t.
The law ends with something I’ve never seen before, a section entitled “Sense of the Senate.”
It’s so strange, I’ll let it speak for itself:
“SEC. 3. SENSE OF THE SENATE.
It is the sense of the Senate that section 561B of the Federal Food, Drug, and Cosmetic Act, as added by section 2—
(1) does not establish a new entitlement or modify an existing entitlement, or otherwise establish a positive right to any party or individual;
(2) does not establish any new mandates, directives, or additional regulations;
(3) only expands the scope of individual liberty and agency among patients, in limited circumstances;
(4) is consistent with, and will act as an alternative pathway alongside, existing expanded access policies of the Food and Drug Administration;
(5) will not, and cannot, create a cure or effective therapy where none exists;
(6) recognizes that the eligible terminally ill patient population often consists of those patients with the highest risk of mortality, and use of experimental treatments under the criteria and procedure described in such section 561A involves an informed assumption of risk; and
(7) establishes national standards and rules by which investigational drugs may be provided to terminally ill patients.”
I’m not sure what it means or why its in the bill, but I like.
Congrats to the Goldwater Institute and all the supporters who made it happen. Hope it helps, and from my perspective, it’s moving in the right direction.
In case you folks are looking for the next thing. Maybe access to some foreign approved drugs for terminal or severely debilitating conditions.
Rick Jaffe, Esq.
A long time ago as a first semester law student, I took the “Legal Method” course on how to read cases, the rules of statutory construction, and generally the analytic tools which lawyers use to analyze the law.
I still remember the professor explaining how sometimes a law is created which makes sense when created, but the reason for the law is later eliminated, but the law continues. He gave the example of the old English common law rule barring civil wrongful death causes of action. Meaning, if one person negligently killed another, the family of the decedent could not sue the wrongdoer/tortfeasor in civil court for damages. The rule made sense when created because in England back then, the property of the wrongdoer would escheat to the state. (Lawyer or neutral phrase for the government taking your property for no good reason). Since the state confiscated the person’s property, there was no point of a civil damage remedy for the surviving spouse or family. Eventually, the escheat law was eliminated for wrongful death tortfeasors, but the wrongful death civil action prohibition continued for a very long time.
Eventually, some anti-authoritarian oddball realized that the wrongful death prohibition no longer made any sense. I have to assume that the-powers-that-be back then had a knee-jerk reaction against the oddball, perhaps trying to invent new rationales for keeping the law, probably something about protecting the general public. But eventually a wrongful death right of action was created.
I think there’s a lot of that going on nowadays in the freedom-inhibiting health care regulatory framework. Meaning and specifically, there are some laws which over-protect us based on an outdated model of the relative access to information by the parties to a health care transaction. If you’re scratching your head about what I mean, here is a more recent and closer example.
But first, a micro course on medical malpractice: There are three elements to a medical malpractice claim; a departure from the standard of care, causation and damages. Unconventional care (alternative medical treatments/integrative medicine. or however you want to call it) is by definition a departure from the standard of care. So even if the patient sought out and consented to unconventional care, the patient can still sue the unconventional care provider for malpractice if the treatment caused injury or harm (including the harm of not undergoing a conventional “effective treatment.”) Although there is a common law defense called “assumption of risk,” it didn’t apply to the doctor/patient transaction because of the perceived imbalance of knowledge between the parties.
This was the law up until the early 1980’s. Let’s try to image what it was like back then where there was no internet, there were just three networks and we listened to disc jockeys who didn’t curse or rant about politics; they just played music. The only medical news we got was from newspapers and the medical sections of the weekly news magazines. (For those of you too young to remember, and as hard as it is for you gen xers to believe, tens of millions of people used to purchase little booklets each week to read about the news, entertainment, science and other public interest matters, all in one glossy booklet/magazine. Quaint stuff for sure).
People who didn’t read the specialized medical literature or go to the medical conferences experienced a relative imbalance of information. And that imbalance was the rationale for not allowing assumption of risk as a defense to a medical malpractice claim. But even in the dark pre-internet era, things changed in terms of our assessment of the imbalance of information between the doctor and patient and assumption of risk. Here’s how it happened.
A woman was diagnosed with early stage breast cancer. Let’s call her Eidth. Her Oby-Gyn and three other doctors told her to have a mastectomy and if she did, she was told she would mostly likely live a normal life. She refused and wanted to go the “natural way.” So she found an alternative cancer doctor in New York. Maybe he told her to get a lumpectomy, which she refused, but he still treated her with some trace mineral elements including selenium which he had been using on cancer patients for decades.
She got much worse despite the treatment and eventually was forced to have a bi-lateral mastectomy. She lived, but she sued the unconventional doctor for malpractice. It was my firm’s first case in the health care field. Because of our lack of experience, we couldn’t understand why assumption of risk wasn’t a viable defense, but all the experienced malpractice attorneys kept talking about the imbalance of information.
As luck would have it, before the trial, the New York Court of Appeals had issued a ruling that a teacher who voluntarily participated in a donkey race in a school gym might not be able to recover for his injuries from falling off the donkey, if he “expressly assumed the risk” of racing on a jack-ass in a gym. Well, our doctor/client wasn’t a jack-ass, but why couldn’t the patient assume the same risk as the teacher. Wasn’t it just an issue of fact whether the patient had all the material information, just like the teacher, and expressly agreed to assume the risk? We thought this whole imbalance metaphor had gone on too long, given the new world of color TV, and high tech glossy magazines. Hell, people had recently begun sending each other pieces of paper and even complete documents over the phone lines with something called a facsimile machine. It was a new world of information and we thought it was time for a change.
We tried to get the federal judge to give an assumption of risk jury instruction, citing the donkey case, but she refused, citing the fact that no New York state case had ever applied the assumption of risk affirmative defense in a medical malpractice case. She was right about that, but someone has to change the law.
The trial resulted in our first million dollar verdict, but of course, since we were defense counsel, it wasn’t such a noteworthy accomplishment. We took the case up on appeal, and in what might be considered a landmark decision, the Second Circuit Court of Appeals created an assumption of risk affirmative defense to a medical malpractice case. The judges felt that if the patient was provided with enough information about the potential risks and benefits, and expressly assumed the risk of the treatment which she knew was technically a departure from the standard of care, then she couldn’t recover against the doctor. Then and now, it seemed like the right result. So my first million dollar verdict was reversed (a good thing for defense counsel).
Because it was clear that the patient really did expressly assume the risk, and maybe because of some good lawyering on our part after the case was sent back for retrial on the sole issue of assumption of risk, the plaintiff’s counsel walked away from the verdict and dismissed the case. (More details about the case in Chapter 1 of Galileo’s Lawyer which will be released in about a week on Kindle, Nook and other eBook places)
So even in the dark ages of the pre-internet, glossy magazines and new-fangled inventions like the fax machine, patients could assume the risk of non-standard treatment. Thirty years later, there is an abundance of medical information available to every human being with a mobile device and access to the internet. You can join web sites where members will diagnose you. Many medical journal articles are available on-line for free and there are hundreds if not thousands of web sites offering advice and medical information. You can go on-line and find every single clinical trial for every single disease. Despite all of the information at the consumer/patient’s fingertips, the government still feels the need to protect a patient from treatment which is literally taken from the patient’s body and put back the very same day. How can that be?
The point is that times have changed. We live in the era of information abundance and google doctoring. Patients have a quantum level more information than was available to previous generations. As a result, patients can and should be given more responsibility for their treatment decisions, or at least for those patients who are willing to assume the risk of less than fully “proven” treatment (which always works). That applies with ever greater force to terminal patients or patients with incurable progressive diseases like MS and ALS. And it applies with even greater force when the so called treatment is just removing some fat from the person’s body, separating the fat from the stem cells and reinjecting the stem cells during the same procedure. These overprotective laws and guidelines seem like the continued prohibition of wrongful death actions after the escheat law was changed.
Because the Kirk/Alexander/Collins/regrow/ replant/explant/exlax, bill reaffirms the FDA’s jurisdiction over some same day autologous stem cell procedures, and particularly adipose to mesychemal transplants, this bill is just as backward as any other effort to come-up with new justifications for laws which don’t make sense anymore.
It is ironic that the FDA’s original interpretation of the key phases –more than minimal manipulation, same surgical procedure and homologous – which led the FDA to decline jurisdiction over basically any same day autologous transplant, gave physicians and patients the ability to make these decisions rather than the FDA. Those were the good old days (pre-2012). Hmmm, so maybe my Legal Method recitation isn’t precisely on point since the FDA’s original interpretation was correct. Oh well, I have always found it to be a lesson worth remembering, and so might you.
Richard Jaffe, Esq.
Galileo’s Lawyer is coming out in EBook next week, Kindle, Nook and apple iBook. Chapter 9 is about the first FDA criminal investigation of a cord blood stem cell transplant clinic.
Recently, a federal right to try bill was introduced in the senate, which is a companion to a bill introduced in the house last summer, HR 3012. I want so bad to feel hopeful and even excited. I’m trying, I really am, but I was deeply involved in similar past efforts, including the bill championed by the heavy weight senators, “the Toms” (Senate Majority leader Tom Daschle and Tom Harkin) along with Congressman Peter DeFazio. I was also around when Dan Burton tried on the Republican side to pass similar legislation. The prior bills generated a lot of excitement from the health activist community, but little from the rank and file congress folk, and relatedly, little excitement or interest from pharma. My recollection is that none of those bill ever made it out of committee, which is where HR 3012 currently resides. Maybe this time it will be different because of the impressive efforts of the Goldwater Institute’s legislative achievement of passing right to try in 28 states (so far). I hope so.
The federal bill is simple. https://www.congress.gov/bill/114th-congress/house-bill/3012/text The FDA can’t interfere with a physician or drug company providing a post phase 1 investigational drug to terminal patients. Sure, there is vagueness in the bill about whether any aspects of current IND law might apply. However, for sure, if passed, the bill would do at least one important thing which is necessary to open up access to pipeline drugs: Me and my fellow health care attorneys will stop advising drug companies that shipping an investigational drug outside of a clinical trial or expanded access is a violation of federal law.
The other really good news is that presumably under this law, the physician no longer has to fill out a lengthy IND application or even the new streamlined two-page expanded access SPP form. The physician can just administer the drug, right? Does the physician have to report adverse events? What obligations does the manufacturer have once it releases the drug to the physician? The same as in an IND or expanded access? Can the sponsor charge the patient for the drug? If so how much? Cost recovery like under current FDA law? Or a greater amount? How long does the drug manufacturer have to keep on supplying the drug to the patient under right to try?
Apart from these technical questions, there is still the one overarching question/problem in the right to try universe: why would drug manufacturer agree to provide their investigational drugs outside of clinical trials or FDA expanded access? Manufacturers haven’t been pushing their drugs into the expanded access program, and there is no reason to think that right to try would change that. The most off-cited reasons for pharma’s past disinterest are: 1. Fear that open access would slow enrollment in clinical trials which would delay drug approval. 2. Fear that negative data from patients who are sicker with more co-morbidities would lessen the chance of, or slow drug approval, and 3. Limited supplies of investigational agents, which could slow approval. It is already ridiculously slow and costly to have a drug approved in this country, and pharma is worried (and rightly so, I might add) that open access will make the process even slower and more expensive.
Pharma’s past and anticipated future reluctance to embrace expanded access of any kind is for me the big head scratcher, and the reason why I’m just not feeling that federal right to try will have a major impact on the large number of cancer patients who might benefit from pipeline drugs. Under current law, and even under federal right to try, there is no incentive for drug manufacturers to provide investigational drugs outside of clinical trials. Sometimes drug companies can be embarrassed to provide access to their investigational drugs, as has happened in the past with some Facebook shaming campaigns. But that’s not the way to get pipeline drugs to large numbers of desperate patients.
So the obvious answer is to give pharma incentives to provide open access to post phase 1 drugs. Most of the time when drug manufacturers provide drugs in expanded access, they do not charge for the drugs, even though theoretically they could seek permission to do so. The main reason is probably that manufacturers can only recover the actual costs, and drug companies don’t want the FDA or the public to know how cheap the drugs are to manufacture.
Some drugs are early-stage developed by relatively small drug companies, some of whom are cash-strapped, and such companies answer to investors. Taking these two facts together suggest one possible incentive: let manufacturers charge a reasonable price above cost recovery. This might provide an incentive to some drug companies to offer their investigational products post phase 1.
The talking-head ethicists and professional policy folk might decry the fact that drug companies are charging for unapproved drugs, but again the population is terminal patients. Some of these patients might believe that the lack of efficacy data and the financial risk of using an unproven or ineffective treatment are worth taking. And let’s remember that essentially all of the almost 600,000 people who die each year of cancer had treatment which didn’t cure their disease. So by the actual measure of treatment success, which is cure, all of these people took treatment or many treatments which were unsuccessful. Someone has to decide when a dying patient should have access to an investigational drug outside of a clinical trial, either a government bureaucrat for the dying patient. Why shouldn’t it be the patient?
Is charging for the investigational drug enough of an incentive to dramatically increase pipeline drug access? Proably not. To get big pharma on board might require big-time additional incentives. Here are a couple possibilities: Give some kind of priority review to companies which provide open access to their drugs. Give consideration to any positive results achieved under expanded access/right to try, but continue the FDA stated policy of not considering negative data because the population is sicker with more co-morbidities than the patients in clinical trials.
You want to really get pharma’s attention? Throw in an extra year or two of patent protection if a drug is made widely available by the manufacturer under federal right to try. Orphan drugs already have this kind of incentive, and that program has greatly helped the development of drugs for rare conditions. The point is that we need to think creatively about incentivizing the drug companies to participate in right to try, both to assist in getting it passed in Congress, and to make it effective in providing pipeline drugs to large numbers of dying patients. The law itself as it is written simply won’t do the job.
Richard Jaffe, Esq.
For almost 40 years, terminal patients have been trying to obtain access to unapproved new drugs. The latest effort has come from the Goldwater Institute (“GI”) which has made the strategic decision to bypass Congress and the federal courts and go directly to the state legislatures. GI’s legislative efforts have been wildly successful, having passed its “right to try” law in more than half of the states. That’s an almost unbelievable accomplishment and everyone should laud and support it, but it won’t do much practically until Congress is forced to act, and act in a big way. Before I go into why the state legislative angle won’t do the job, let’s review how we got to where we aren’t, namely open access to pipeline (and other) drugs for very sick people who can’t be helped by FDA approved drugs. The history is instructive.
It started with laetrile in the 1970’s when terminal cancer patients sued the FDA for access to the apricot pit based cancer remedy. A compassionate and brave Oklahoma federal district court judge held in part that the FDA’s attempt to keep laetrile from terminal patients violated their constitutional privacy rights. https://www.courtlistener.com/opinion/1554980/rutherford-v-united-states/.
The court of appeals affirmed the result, but on a different ground, holding that as a matter of statutory interpretation, the FDA’s safety and efficacy requirements do not apply to terminally ill patients. The appellate court created this non application of safety and efficacy requirements because it wanted to give the patients laetrile but like most federal appellate courts, it wanted to reach the result without making a constitutional ruling. So the court decided that the statute didn’t apply to terminal patients.
In 1979, the liberal Supreme Court unanimously reversed the court of appeals. Ironically, Thurgood Marshall, – the man who argued Brown v Board of Education (“separate is not equal”) as a lawyer – wrote the opinion that there was no statutory exception to FDA law for terminal patients. Marshall ducked the district court’s right of privacy holding because the court of appeals hadn’t addressed it. The Supreme Court remanded the case to the court of appeals to decide the constitutional privacy issue. http://caselaw.findlaw.com/us-supreme-court/442/544.html. The appeals court decided that terminal patients do not have a right of privacy to take medicine of their choosing.
And so ended the right of privacy for terminal patients. The right has stayed dead or nonexistent until this day, despite efforts by lawyers (including me) to revive it.
Interestingly, even though the federal government denied dying patients’ access to laetrile, many states stepped-up to the plate and passed laetrile access laws. Technically, these laws were in conflict with federal law, in the same way as the state laws legalizing marijuana are in violation of federal law. However, then as now, the feds basically let people have access in the states in which it is legal, or at least the feds didn’t go after the patients. The state laetrile laws in the 70’s may have been an inspiration to the right to try movement, but ultimately it is a false analogy, as I will explain later.
Access to unapproved drug was raised indirectly in Texas in the Burzynski cases in the 80’s and 90’s. In the early 80’s, a Texas judge held that although Burzynski couldn’t ship his unapproved drugs across state lines, he could provide them to patients in Texas since it appeared to be legal there. In response, the Texas legislature closed the loophole by passing a “mini-FDA act” which made the treatment illegal in Texas.
The issue came up again in Burzynski’s criminal case in the mid 1990’s when a Texas district court held that under Burzynski’s conditions of bail, he was not permitted to give his unapproved new drug to patients. We ended up going to Congress for help. Congressman Joe Barton and some the Burzynski patients forced the FDA to back down, and the FDA provided a legal way for Burzynski’s patients to get the unapproved drug. (The FDA put all of his patients on a clinical trial protocol. See chapter 2 of my book, Galileo’s Lawyer for a more detailed discussion. http://www.amazon.com/Galileos-Lawyer-Alternative-Complementary-Experimental/dp/0980118301. The book’s discussion about how that took place and my characterization of this one clinical trial protocol as a “joke” has become an oft repeated blog and media topic, much to my dismay. But more about another time.). The Burzynski access issue relating to his bail conditions also prompted congressional hearings on access in general, but nothing came of it.
In the late 1990’s, and early 2000’s, there were other efforts to legislatively open up access to unapproved drugs. One was the Thomas Navarro house bill submitted by former Congressman Dan Burton. Thomas was a young terminal brain tumor patient who was initially refused access to Burzynski’s treatment. Thomas and his right to get treatment was discussed in a 2000 Republican presidential debate. However the bill went nowhere.
In the 2000’s there was another serious litigation effort in the form of the Abigail Alliance case based on a heart-wrenching story like Thomas Navarro’s. Like the laetrile case, a brave district court judge opened-up access to unapproved drugs on a constitutional basis. However, the DC circuit court overturned the lower court, holding that only the all-knowing FDA has the right to determine what drugs dying patient can take. https://en.wikipedia.org/wiki/Abigail_Alliance_for_Better_Access_to_Developmental_Drugs_v._von_Eschenbach.
Patient access to investigational drugs hasn’t gone completely unnoticed by the FDA. Because of the AIDS epidemic, since 1987, there has been some form of expanded access, i.e., access to investigational drugs beyond enrollment in clinical trials. Originally called “compassionate use” or “special exception” access. More recently expanded access has, well expanded somewhat, and is now called single patient protocols. There are other larger programs as well (e.g. Treatment INDs for bigger groups). The FDA has even recently streamlined the SPP approval process with the introduction of a two page form instead of a formal IND. (more about that another time) However the FDA’s program is still woefully inadequate. Less than two thousands patients a year are treated under SPP’s, which is a miniscule amount compared to the amount of patients who could benefit from access to investigational drugs.
Which leads us back to the Goldwater Institute’s right to try state legislative efforts. I think it’s now law in 28 states. Although there are some differences in the laws, the basic state law provides that medical doctors cannot be charged with a medical board violation for providing seriously ill patients with an investigational drug which has completed phase 1 (safety) clinical trials. Many of the laws purport to make it legal for drug manufacturers to provide the investigational drugs to patients. Some states disallow charging for the drugs, others allow it. Proper informed consent is required.
Of course, the physician and the patient have to obtain the investigational drug from the drug manufacturer, and therein lies the problem. There is and cannot be any way a state can compel a manufacturer of an investigational drug to give or sell it to a patient outside of clinical trials or expanded access. And from there, it just gets worse.
Suppose the drug manufacturer is in a different state from the doc? Can the manufacturer ship an investigations drug across state lines to a physician to administer to a patient in a right to try state? I don’t see how. The right to try law does not and cannot immunize a manufacturer from the federal law violation of shipping an unapproved new drug across state lines. The “law” just doesn’t work that way. While the federal government may not go after Colorado marijuana sellers who sell product to people in Colorado, if any of those sellers start shipping weed out of state, I guaranty the feds would shut them done very quickly.
Similarly, I don’t see how it would be legal for a drug manufacturer to ship an investigational drug across state lines without violating the FDA criminal statutory trifecta (introducing into interstate commerce an unapproved new drug, misbranding and adulteration). What interest would the FDA have in allowing that? None that I can think of. Depending on your perspective, for better or worse, the FDA is intent on controlling the use of investigational drugs and I don’t see it ceding any part of that power to the states.
Furthermore, I don’t see how any competent FDA attorney could advise a drug manufacturer to ship an investigational drug across state lines for use outside of a clinical trial or under formal FDA expanded access.
But even if a manufacturer is in the same state as the administering doctor, based on past precedent (the Regenerative Sciences case discussed in my first stem cell post), dollars-to-donuts the FDA would take the position that if the drug manufacturer buys a test tube or a pencil from an out-of-state source, that’s enough interstate commence for the FDA to assert jurisdiction over the intra state distribution of the investigational drug. But even without the out-of-state purchase of a pencil, the FDA, backed up by federal jurisprudence, has a jurisdictional predicate of “affecting interstate commerce.” Basically, everything affects interstate commence in some way. So lawyers should be telling drug manufacturers that it is not FDA legal to ship unapproved drugs out of state or even within a state, for anything other than an FDA clinical trial or FDA expanded access. And on this I speak from professional experience.
But there is a bigger problem based on the naked realities of self-interest. There is only one reason a drug manufacturer tests an investigational drug; to get the FDA to approve it for marketing (so the executives can get their bonuses and/or cash-in their stock options after approval).
Why would pharma execs risk the FDA’s wraith to provide their investigational agents outside of FDA sanctioned expanded access programs? To save patients’ lives? Oh please, you’re listening to too many pharma commercials. Pharma hasn’t even provided wide access to investigational drugs under FDA expanded access, so it’s completely unrealistic to think it will do so in technical violation of federal law.
Going back to laetrile: The state laws legalizing it were effective in allowing access to the drug, but only because the suppliers of laetrile were not pharma beholden to the FDA for drug approval. They were mom-and-pop, cottage industry folks from the herb and supplement field who didn’t give a whit about the FDA or drug approval. Pharma lives and dies in its relationship with the FDA, which is why there is the obscene revolving door between senior FDA regulators and pharma companies.
There is another hard reality. The right to try target group consists of patients who are likely sicker or much sicker than patients who could get the drug in a clinical trial. Why? Because right to try covers terminal patients, and mostly very sick terminal patients who have tried and failed other treatments. These patients usually have many co-morbidities. Drug companies prefer to test their investigational agents on the healthiest people they can find for the drug’s indication. That’s what the entry criteria in the clinical trial protocol are all about. Why? Healthier people have fewer co-morbidities and will experience fewer side effects which could be attributed to the study drug. Side effects have to be reported or at least recorded. Although the FDA says that side effects (adverse events “AE’s” or serious adverse events “SAE’s”) for SPP’s and compassionate use do not negatively impact a drug approval decision, drug companies don’t believe it. And they are worried that after approval, evil plaintiffs’ attorneys will use these SAE’s against the company in products liability cases. For these reasons, the drug companies are not and will not buy into the whole bypassing of federal law, state right to try thing.
So what’s the point of right to try? For starters, it is a direct and impressive manifestation of the will of the people. It is very important for federal legislators to hear what people want, to give them the impetus to reign in the FDA. If all or most states pass right to try, I think Congress will have to act.
What kind of new federal law? Maybe there needs to be a new business model for drug approval. I would propose patient funded access to early stage investigational drugs, as a choice for patients. That might entice some smaller drug companies to open up access.
At its core, the issue is who has the right to decide on treatment for dying patients? Is it government bureaucrats, talking heads in the cancer establishment, professional ethicists, mentally disturbed bloggers (more about that another time), or the dying patient and his or her family. Guess where I stand?
This is a bigger issue than right to try, or federal expanded access, both of which require that a drug be in a formal clinical trial before it is available to a patient. I go the next step, and re-ask the question I asked in the title. Why can’t dying patients have ANY drug they can get their hands on? I do not think the federal government should be in the business of overseeing or limiting the kinds of drugs or remedies which a terminal patient can take. I think a dying patient should be able to get any drug he/she can get their hands on, and let them weigh the risk and make the decision.
Let’s circle back to the laetrile case. I think the court of appeals got it right when it said that the FDA’s safety and efficacy requirements should not apply to terminal cancer patients. These patients should be able to make their own decisions and take whatever treatment they want. Those terminal patients who want the full and glorious protection of the federal government and the mainstream cancer establishment can limit their treatments to FDA approved drugs and drugs in clinical trials or expanded access. But what right does the federal government or so-called cancer experts have to limit options for people who have no potentially life-saving options?
Each year almost 600,000 people a year die of cancer. I would venture to say that every one of them had some kind of treatment and died on it, as a result of it, or at the very least, the treatment they received obviously did not prevent their death. And the same is true with other diseases. This is a liberty issue. Either the patient or the government makes these decisions. Right now it’s the government. I think it should be the individual patient.
So the “go big or go home” solution is simple. Remove the FDA’s jurisdiction over terminal patients. That’s what the Tenth Circuit Court of Appeals did in the laetrile case, and 40 years later, it’s still the best solution I’ve ever heard. I think many people would agree.
Richard Jaffe, Esq.