There are times when supporting science-based health policy and opposing health policies that sound compassionate but are not are easily portrayed as though I’m opposing mom, apple pie, and the American flag. One such type of misguided policy that I’ve opposed is a category of bills that have been finding their way into state legislatures lately known as “right to try” bills. Jann Bellamy over at SBM and I have both written about them before. With the passage of the first such bill into law in Colorado in May, followed by Missouri and Louisiana, and its heading to the voters of Arizona as a referendum in November, I had been meaning to revisit the topic. Although “right-to-try” laws are a bad policy idea that’s not new, versions of such bills having been championed by, for example, the Abigail Alliance for at least a decade, the recent popularity of the movie Dallas Buyers Club appears to have given them a new boost, such that Colorado state Senator Irene Aguilar even frequently referred to her state’s right-to-try bill as the “Dallas Buyers Club” bill. It’s a topic I’ve been meaning to revisit at least since the news out of Colorado in May, but apparently I needed a nudge, given that it’s two months later now.
Unfortunately, that nudge came in the form of a right-to-try bill (Senate Bill 991) introduced into the legislature in Michigan by Senator John Pappageorge. It was unanimously passed, almost without comment, by the Michigan Senate Health Policy Committee, and certainly there was minimal news coverage. Moreover, I just learned that it was being taken up by the Senate yesterday. In parallel, the same legislation (House Bill 5651) has been introduced into the Michigan House of Representatives.
I joke (somewhat grimly) about seeming to be opposing mom, apple pie, and the American flag (not to mention apparently also about wanting to disembowel puppies) when I discuss right-to-try bills, but there’s a reason for that. These bills tend to have not just broad bipartisan support in the legislature, because opposing such laws seems on the surface to be the equivalent of denying dying patients a last ditch chance at life, but broad support among the public because of the seemingly reasonable question, “What’s the harm?” Unfortunately, disaster can result when normal human compassion for fellow suffering humans is yoked to misinformation and misunderstanding of science (in this case how clinical trials work), who really controls drug development and regulation in the US, and the real harm that using such drugs prematurely can cause. For right-to-try, the result is perniciously popular legislation that provides lots of false hope and virtually no benefit to terminally ill patients. In the face of this, even politicians with a reasonable understanding of the science, why such laws represent nothing but false hope, and why, even if they go into effect without objection by the FDA, would be far more likely to harm patients than help them, hesitate.
Right-to-try in Colorado
Before I get to my own state, let’s look at Colorado’s right-to-try law, since it was the first to pass. One thing that I feel obligated to point out again is that virtually all the recent “right-to-try” bills introduced into state legislature have been based on model legislation designed by the Goldwater Institute, a libertarian think tank whose specious and misleading arguments for such legislation I’ve discussed before . In her previous post on right-to-try bills, Jann Bellamy mentioned that there is “nothing like a touching anecdote to spur a politician into action,” and she’s right. That’s why the Goldwater Institute’s web page on its right-to-try initiatives is populated with intentionally emotionally manipulative heart-wrenching testimonials of (mostly) cancer patients arguing that, if only they had had access to experimental drugs, they might survive or of dead patients whose family or friends tearfully argue that “if only”—if only—right to try had been passed before their loved one died that loved one might still be alive. In the wake of the passage of Colorado’s right-to-try law in May, anecdotes ruled, heart-wrenching anecdotes such as this one about Nick Auden, a Colorado man with stage IV melanoma who died six months before the legislation passed:
Who isn’t moved by the struggles of a father who wants to survive for his children? Who wouldn’t want to help this man? What kind of monster am I to oppose a law that would provide brave suffering patients like Nick Auden another shot at life, no matter how slim the chance? Such is the level of discourse directed at those who have the temerity to point out that right-to-try laws are a sham, false hope, and far more likely to harm terminally ill patients than help them; that is, if they have any effect whatsoever, which is unlikely. They are what I like to call placebo laws in that they make the body politic feel better but have no real effect on the underlying problem that they are meant to address. Indeed, as Jann Bellamy pointed out, a much less emotion-driven analysis of these so-called “right-to-try” bills currently before several state legislatures reveals disturbing truths about the false promises behind these bills, promises which in some cases appear to be driven more by political ideology than genuine concern for patients.
This can be seen by a simple comparison of the text of the Goldwater Institute model legislation and the final text of the Colorado right-to-try law as enacted. The Colorado law, in fact, bears a very close similarity to the Goldwater Institute model legislation. Some differences between the Goldwater Institute template and the actual Colorado law that leapt out at me included that the Colorado law:
- Adds a mention that the drug approval process in the US “protects future patients from premature, ineffective, and unsafe medications and treatments over the long run, but the process” (not in the Goldwater template text) and “often takes many years” (in the Goldwater text)
- Alters eligibility to include patients who have “been unable to participate in a clinical trial for the terminal illness within one hundred miles of the patient's home address for the terminal illness, or not been accepted to the clinical trial within one week of completion of the clinical trial application process”
- States that “an insurer may deny coverage to an eligible patient from the time the eligible patient begins use of the investigational drug, biologic product, or device through a period not to exceed six months from the time the investigational drug, biologic product, or device is no longer used by the eligible patient; except that coverage may not be denied for a preexisting condition and for coverage for benefits which commenced prior to the time the eligible patient begins use of such drug, biologic product or device”
There are other differences, of course, but they’re mostly wording and Colorado-specific language about state statutes effected. I tend to interpret #1 as having been added to make it sound less as though the FDA approval process is useless, as the Goldwater text does. My guess about #2 is that it was undoubtedly added in order to exclude patients who just want experimental drugs but aren’t interested in enrolling in a clinical trial. Finally, I’m not completely sure how to interpret #3 and would welcome a lawyer’s input (particularly if it’s a health lawyer), but it sounds rather ominous in that it allows insurers to deny new coverage to a patient for a six month period from the time the patient starts use of an investigational drug, but can’t deny coverage for a preexisting condition (i.e., the condition that led the patient to be terminally ill, and any other preexisting conditions) or any benefits that commenced prior to the time the patient starts using an experimental drug or device. On the other hand, to me the language implies that insurance companies can deny coverage for any complications that arise from the use of experimental therapy under right-to-try, whether caused by that therapy or not. So if the patient develops a complication from the treatment, he’s out of luck. If he happens to be hit by a car, he might be out of luck. Thus, a bill that sounds compassionate appears to have a cruel, punishing twist embedded in it.
That is not in the least bit surprising. This law is very “libertarian” in that it says that patients can try an experimental therapy that’s passed phase I trials to phase II or beyond, but anything that happens after that is all on the patient. (Indeed, my interpretation of right-to-try is that it would allow access to a drug that's only passed phase I, even if the phase II trial hasn't accrued a single patient yet, as long as there's a phase II trial open.) The doctor recommending the treatment is off the hook, no matter how bad his decision to recommend the experimental therapy was. The drug company is off the hook, no matter how many problems the drug might have. The insurance companies appear to be off the hook, complete with a potential loophole to let them refuse to cover various treatments in terminally ill patients. Basically, if you’re rich, you can bypass clinical trials (if the company is willing) and buy up experimental drug for yourself. If you’re poor, or even just not rich (remember, these drugs will cost big time), you’re, as they say, SOL. You can have the hope dangled in front of you and just die. No wonder the Goldwater Institute flew a flack to Lansing last month to testify about the bill, as it appears to be doing for every state considering right-to-try legislation.
At this point, I think it’s a good idea for me to remind my readers once again that that these right-to-try laws cover any drug, treatment, or experimental device that has passed phase I clinical trials. Indeed, in the video above, the reporter made a highly misleading statement when she stated that the Colorado “right-to-try” law “only applies to drugs that have been deemed safe by the FDA.” That statement is so wrong it’s not even wrong, as skeptics sometimes like to say. Just because a drug has passed phase I clinical trials does not—I repeat, does not—mean that the drug has been “deemed safe by the FDA.” Phase I trials, also known as “first in human” trials, don’t enroll very many patients. Sometimes it’s as few as 20 patients, sometimes even less. That is not enough to adequately determine safety, nor is it intended to. That’s because phase I trials are designed primarily to identify major side effects and to use a process known as dose escalation to determine what is commonly referred to as the “maximum tolerated dose” (MTD). It is utterly impossible for such a small clinical trial to adequately assess the safety of a drug. All it can do is to make sure there are no unexpected major adverse events, that the expected side effects are tolerable, and that the drug has a side effect profile that isn’t grossly more unsafe than the disease itself. Phase II and phase III trials are needed to confirm safety. That’s why the premature diffusion of unapproved drugs has the potential to increase morbidity from adverse events and even hasten death. One example is amonifide for treating breast cancer. The drug made it through phase I trials, but serious life-threatening hematologic toxicity emerged during phase II trials.
Think of phase I trials as a screening test looking for the most obvious toxicities, with phase II and III studies confirming them. Indeed, even phase III trials can’t always adequately demonstrate that a drug is safe; it’s not uncommon for less common adverse effects not to show up until post-marketing surveillance, when much larger numbers of patients receive the drug. Moreover, only 5% of all cancer drugs that enter clinical testing are ultimately approved for patient use. Among drugs tested in phase II trials, only 30% go on to phase III. So, to equate having passed phase I clinical trials with having been “deemed safe by the FDA” betrays a profound misunderstanding at the heart of the bill of what a phase I trial is and what passing it means. The potential for disaster is there.
The false hope of right-to-try metastasizes to Michigan
I’ll discuss more of what’s wrong with right-to-try laws and how misguided they are, but first I want to take look at the right-to try bills currently under consideration in the Michigan legislature. Oddly enough, I was completely unaware that a right-to-try bill had been introduced into the Michigan legislature until last month, when I got a message from a concerned person. It had basically already passed committee. Before that contact, as hard as it is to believe right now, I had heard absolutely nothing about these bills, but I’m a fast learner. I didn’t have much help, though, because there was very little media notice taken of the Senate hearing about this bill other than a Detroit Free Press article that I found days after the hearing and self-serving articles on John Pappageorge’s website touting mistakenly how this bill would allow “access to potentially life-saving treatments.” Either that, or I missed it because I was out of town at TAM in the days leading up to the hearing. Now, I hear that the bill is being debated in the Senate, but yesterday I couldn’t find a single news article about it. It was sneaked in, apparently, and I only heard about it because an interested activist let me know.
Now, going back to look over the coverage, I found that the Freep article bought in the same compassionate but incorrect framing as was the case in the other states considering such laws:
Arlene Kalley has lived with terminal cancer for years — and with each new drug she uses to keep the disease at bay, her options dwindle.
Earlier today, the Michigan Senate’s health policy committee approved a bill that would offer Kalley and other terminally ill patients in Michigan better access to experimental medication.
It doesn’t require manufacturers to provide the drug nor does it require insurers to cover the costs. But it gives patients a “right to try,” said Sen. John Pappageorge, R-Troy, whose first wife died of cancer in 1993.
He introduced the bill earlier this year after speaking with Terry Kalley, a partner with Global Logistics Strategies in Bloomfield Hills.
And this is how the idea for introducing bill came about:
His wife, Arlene, was taking Avastin in 2011 to keep metastatic breast cancer at bay when the U.S. Food and Drug Administration yanked its approval of the drug, questioning its safety and efficacy.
Ultimately, Arlene Kalley was able to keep taking Avastin because it still was being used to treat other cancers, but the experience got the Kalleys thinking about what could happen if Arlene Kalley’s current treatment is no longer effective one day.
While I can understand why this case might have led the Kalleys to wonder about right to try, I must point out here that Avastin was a very different case than situations envisioned in right-to-try legislation. Specifically, Avastin had undergone randomized clinical trials (RCTs) beyond phase I and had already been approved for other cancers before being approved by the “fast track” approval process for advanced breast cancer. Its approval for advanced breast cancer was based on two RCTs that showed a modest increase in progression-free survival (PFS) when Avastin was added to chemotherapy, but no effect on overall survival (OS). In 2008, based on a program to “fast track” promising drugs that was developed in 1990s, the FDA gave provisional approval to Genentech to market Avastin for metastatic breast cancer with the condition that Genentech had to perform additional studies to verify the results upon which the original approval had been based. At the time, there was a great deal of argument over whether this was a wise decision, particularly given how expensive Avastin is and the lack of evidence that it improved quality of life or overall survival. Unfortunately, the results of those additional clinical trials were very disappointing to all of us who take care of breast cancer patients. The AVADO trial only found an increase in PFS of less than a month when Avastin was added to docetaxel with no increase in OS, while the RIBBON-1 trial found an improvement in PFS of 2.9 months when added to capecitabine, and 1.2 months when added to anthracycline-based chemotherapy. That’s why in July 2010 the FDA advisory committee revoked the fast track approval.
In other words, although I realize that Arlene Kalley was simply worried about what her options would be if her current treatment regimen ceases to keep her cancer in check, in a manner of speaking she is inadvertently comparing apples and oranges in a way that could lead those unfamiliar with the Avastin saga to believe that Avastin and right-to-try are related by anything other than the fact that she has done well on Avastin thus far. I bring this up because the saga of Avastin for breast cancer is relevant to right-to-try bills, but not in the manner implied. Contrary to the arguments made in favor of right-to-try laws that a single phase I trial is enough for a treatment to be deemed "safe," even though Avastin was FDA-approved for other cancers and provisionally approved for breast cancer, in the subsequent clinical trials for advanced breast cancer there was evidence of harm due to Avastin. That harm likely accounted for why the increase in PFS did not translate into an improvement in OS. Specifically, the drug’s toxicity likely “took back” those gains in PFS. As Fran Visco of the National Breast Cancer Coalition put it, “The FDA should never have approved Avastin for breast cancer to begin with. We don’t see evidence of benefit, but we do see evidence of harm.” And that was just Avastin, not a drug with much less extensive testing, such as the experimental therapies right-to-try bills propose releasing “into the wild,” so to speak.
So what do the Michigan bills SB 991 (Senate) and HB 5651 (House) propose? It’s basically very similar to the Colorado law and the Goldwater Institute boilerplate, with a couple of notable exceptions. For example, SB 991 requires:
- A statement in the “written informed consent” for using the experimental drug that informs the patient that “the patient's eligibility for hospice care may be withdrawn if the patient begins curative treatment and that care may be reinstated if the curative treatment ends and the patient meets hospice eligibility requirements.”
- A statement in the “written informed consent” for using the experimental drug that attests that the “patient understands that he or she is liable for all expenses consequent to the use of the investigational drug, biological product, or device and that this liability extends to the patient's estate, unless a contract between the patient and the manufacturer of the drug, biological product, or device states otherwise.”
The first of these is odd and unnecessary in that hospices tell patients up front that if they undertake curative treatment again they are no longer eligible to be in hospice while undergoing the treatment. Including such a provision in SB 991 strikes me as redundant, a duplication of law and policy that already exists for hospices. The second of these is to me quite objectionable. Not only does it put the patient on the hook for any expenses or debt that he incurs using experimental treatments, but it seems custom-made for drug companies, to make sure that they get their money for experimental therapies administered under “right-to-try,” no matter what, even letting them go after a deceased patient’s estate, something that will frequently be necessary because patients eligible for "right-to-try" by definition have a terminal illness. The vast majority of even the most promising drugs will likely only prolong their life at best, not save it. Either way, both of these Michigan provisions make a bad bill even worse.
In fairness, though, there is also a provision that explicitly states that a patient’s heirs are not liable for outstanding debt related to the treatment or lack of insurance and specifies that this act “does not affect any mandatory health care coverage for participation in clinical trials under the insurance code of 1956, 1956 PA 218, MCL 500.100 to 500.8302,” which, unlike the truly vile language in Colorado’s law, means that insurance companies must continue to cover all treatments not related to the experimental treatment. Also in fairness, SB 991 does add a provision to the usual Goldwater Institute boilerplate that states that “an official, employee, or agent of this state shall not block or attempt to block an eligible patient's access to an investigational drug, biological product, or device” by adding that “counseling, advice, or a recommendation consistent with medical standards of care from a licensed health care provider is not a violation of this section.” As faculty at a state institution, I would have been very worried about the part about not blocking access as a provision that might get me in trouble if I were simply to voice my medical opinion.
There was also a curious substitution resulting in a “substituted bill” for SB 991 that stops referring to “terminal illnesses” and instead refers to such illnesses as “advanced illnesses”:
(a) "Advanced illness" means a disease or medical or surgical condition with significant functional impairment that is not reversible even with administration of current federal drug administration approved and available treatments that is expected to result in death or a state of unconsciousness from which recovery is not expected. For purposes of this act only, advanced illness has the same general meaning as terminal illness has in the medical community.
For the life of me, I can’t figure out why this change was made, when the substituted bill states that for the purposes of this bill “advanced illness has the same general meaning as terminal illness has in the medical field.” I can’t help but get a sneaking suspicion, which could be wrong, that perhaps the bill’s sponsors are already thinking ahead to eventually expand eligibility for right-to-try to patients who are not terminally ill by laying the groundwork to have “advanced illness” associated with right-to-try rather than just terminal illness. That would fit in with the general anti-FDA tenor of the Goldwater Institute and much of the movement pushing these bills. Remember, the Goldwater Institute wants to turn back the clock at least 50 years, stripping the FDA of its powers gained after the thalidomide tragedy. I could be wrong, of course, but I don’t think so. Alternatively maybe there’s some regulatory or political reason for the substitution. Either way, the Michigan right-to-try bills are in some ways worse and in some ways not as bad as the Colorado right-to-try law. That doesn’t change how much these laws are flawed in their very conception.
The problem with right to try
I can understand the desperation of families, at least, facing the loss of a loved one to a terminal disease, be it cancer or something just as bad or even worse, such as amyotropic lateral sclerosis (ALS), more commonly known to the public as Lou Gehrig’s disease. After all, it was only five years ago that my wife and I faced the death of her mother from metastatic triple negative breast cancer, including brain metastases. Knowing, as all cancer doctors do, that it could happen to me (particularly now that I’m on the wrong side of 50), I can’t even guarantee that I wouldn’t be tempted by the siren call of right-to-try were one of these bills, or some variant thereof, to be passed into law in Michigan and I later was diagnosed with a terminal illness.
Even so, when people ask, “What’s the harm? and “How can it get worse?” I know that there is harm and it can get worse. If there’s anything worse than dying prematurely of a terminal illness, it’s accelerating your demise, suffering unnecessarily during the little time you have left, and/or emptying your bank account while doing either or both of these things. Compassion impels us to want to help terminally ill people in any way we can, but a less emotional analysis of right-to-try bills, coupled with a knowledge of the science and conduct of clinical trials reveals that these laws, as currently constituted, are almost universally a bad idea. Indeed, with such a low bar for a drug or device to qualify for right-to-try (a single phase I trial), it’s almost guaranteed that such laws are highly unlikely to help, at the cost of a not-insignificant risk of causing harm. These laws would be less odious if the bar had been raised a bit, for instance requiring that at least a phase II trial before a drug is eligible, but that's not what any of these bills propose, including Michigan’s.
Right-to-try laws also provide false hope. For one thing, these laws rest on a faulty assumption that there are all sorts of “miracle drugs” out there that can save the lives of terminally ill patients if only the FDA would get out of the way and let the patients have them. This assumption becomes rapidly apparent perusing the Goldwater Institute’s pages on right to try, which is packed with loaded language about the FDA and terminally ill patients, with every experimental drug apparently “potentially life-saving” and patients dying because they can’t get these drugs. Besides the greater likelihood of resulting in patient harm than help, contrary to what their advocates promise, right-to-try laws won’t deliver increased access to experimental drugs. The reason, as Jann and I have both explained at more length before, is because the federal government, through the FDA, controls drug approval, and federal law trumps state law. State right-to-try laws have no power over the FDA, and nothing states can do can compel the FDA to abide by their right-to-try laws. Moreover, drug companies are understandably reluctant to allow just anyone the use of investigational drugs still in clinical trials, because if something bad happens it could very well affect their application for approval:
However, companies and regulators alike have expressed some hesitancies about the program. For companies, expanded access means letting products out of tightly controlled and heavily monitored environments, potentially subjecting the product to incorrect use and previously-unknown adverse events, which would still need to be reported to FDA. Such incidents could potentially raise questions for regulators, thereby harming the chance of a product getting to market. Further, some companies have expressed their fears about expanded access programs robbing their clinical trials of some patients, which could reduce the statistical validity of a trial and potentially harm other patients by delaying a drug's path to market.
Another issue is a practical one. Manufacturing a new drug for the first time is expensive, which is why, quite often, only enough is manufactured to supply approved clinical trials to be used to support an application for FDA approval. “On-demand” manufacturing would not be easy to implement, particularly if enough patients asked for the drug under right-to-try. This could be a particular problem for small biotechnology companies, which often can barely scrape together the capital to do the necessary clinical trials to support FDA approval. Given that these small biotech companies are often the most innovative and least likely to be seeking approval for “me-too” drugs, the effect of right-to-try on the pharmaceutical industry’s already weak innovation could be significant.
It’s also important to note that right-to-try laws are more about ideology than science. Proponents and supporters of right-to-try tend to use arguments very similar to those used by the “health freedom movement” that rely on questions like, “Who owns you?” and appeals to the belief that the government shouldn’t tell people how they should manage their health. For instance, the Alliance for Natural Health USA, a key “health freedom” organization that advocates relaxing laws regulating the practice of medicine, the better to let quackery (particularly “natural treatments” flourish, is very much in favor of a federal version of “right-to-try,” which is every bit as much a bad idea as the state right-to-try laws, given that it would actually do something. As I alluded to above but did not explain, the Goldwater Institute, in an article promoting right-to-try, gives itself away by bemoaning the expansion of FDA authority in the 1960s by the Kefauver-Harris Amendments that required that the FDA not just require demonstration of safety but of efficacy as well before approving new drugs. This expansion of FDA power was in reaction to the thalidomide debacle, leading the Goldwater Institute to make the bizarre argument that because the issue with thalidomide was a safety problem, not an efficacy problem and because thalidomide was never approved in the US (mainly due to the FDA, let’s not forget), the expansion of FDA power in response to the thalidomide debacle was “unwarranted.”
Unfortunately, right-to-try bills and laws are nothing but feel-good measures that provide the illusion of actually doing something without actually doing anything substantive to help desperately ill patients, particularly given that the FDA already has an expanded access program to allow patients to use drugs outside of clinical trials. There are estimated to be 1,000 requests per year now, and it is uncommon for the FDA to deny a request for expanded access. Indeed, in FY2013, only three such requests were denied; in 2012, four; in 2011, one; and in 2010, sixteen. If, as proponents of these bills believe, expanded access programs aren’t easy enough to access, the answer is not to pass state right-to-try laws. It’s to reform the FDA’s expanded use program, something that’s occurred before and is ongoing, just as the FDA has developed a “fast-track” approval program, the same one under which Avastin was approved.
As David Kroll pointed out, true compassionate use reform will require that we as a society come to an agreement about the balance between access and scientific rigor, realizing that unapproved drugs, particularly the biologicals, such as monoclonal antibodies (which are very tricky to manufacture), are often in short supply. It doesn’t help terminally ill patients if patients demanding right-to-try put companies in a dilemma in which they either surrender some of their precious stock of investigational drug for “right-to-try” requests, thus endangering the company’s ability to conduct proper clinical trials, nor does it help patients to spend their life’s savings on investigational drugs that are unlikely to help them and could hurt them. Although their supporters are well-meaning and sincerely think they are helping the most desperate of their fellow human beings, right-to-try laws are a cruel sham perpetrated on terminally ill patients and should be opposed wherever they metastasize.
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Maurice Saatchi (see http://en.wikipedia.org/wiki/Maurice_Saatchi,_Baron_Saatchi), A former advertising executive, given a seat in the UK House of Lords in recognition of his support for the Conservative party, has submitted a bill along these lines in the UK. The bill has been promoted with the full weight of an advertising company behind it - including an editorial article written by the promoters of the bill (but without declaring the COI, so it would appear they were written by an independent journalist).
Fortunately, there has been a considerable reaction on twitter as well as in the medical press (e.g. http://www.bmj.com/content/348/bmj.g3464) and the mainstream media (e.g. http://www.theguardian.com/science/brain-flapping/2014/may/21/saatchi-m…).
Yeah, the last time I discussed right to try, I included a section on the Saatchi bill, which is clearly cut from the same cloth as American right to try bills:
The main difference in the US is that right to try is clearly intended as a step towards neutering the FDA and bringing us back to a libertarian paradise in which the FDA has minimal power over drugs and drug companies will, through the power of the market, magically make sure their drugs are safe and effective, because, you know, the market. They also say that the tort system will keep drug companies in line, which is hilarious, because the Goldwater Institute also does its best to neuter consumer protection laws that would let people harmed by drugs sue the manufacturer. I also note that the Goldwater Institute template for right to try laws explicitly eliminates liability for drug companies and doctors for almost anything associated with the use of experimental therapeutics.
One point I'm missing....would the drug companies be required to provide the drugs...even if they are still unapproved and in short supply? Couldn't companies just say they are not available? I'm not sure I'm seeing how this bill would transfer the drugs from clinical trials to "me to" patients.
Other than that point, I'm so glad you are addressing these "feel-good" bills. Thanks.
Regarding item 2 in the Colorado law, the 100 mile radius provision isn't facially absurd, because people who are seriously ill often can't travel long distances. Except that the people who live in those places are overwhelmingly likely to be poor, so the "caveat emptor" wording of item 3 is a major problem. I'm assuming that trial sites would tend to be hospitals or clinics in big cities and/or affiliated with major universities, which in Colorado basically means the Front Range region (Pueblo to Fort Collins, including metro Denver)--most of the money in the state is either there or in the mountain resort towns, and the latter have a high concentration of second homes. As for enrolling within one week, that depends on how long it typically takes to enroll a patient (on which point I have no knowledge), but if the paperwork normally takes more than a few days, yes, that's a problem.
As for these John Galt wannabes who think we should do an end run around the FDA: The FDA exists for a reason, and the reason has to do with the outcomes of the last time we had the sort of regulatory regime they advocate.
I have familiarity with some research protocols. I'm not sure I get the one week thing.
Usually they know right away if you meet the eligibility criteria or not and consent you right away (although depending on the trial it may take more than a week from consent to your first study visit as it depends on the schedule of the doctors/clinics involved as they usually see regular patients as well so only have so many study visits per week). Although sometimes you do get what is called a deferred status if you are waiting for medical records from a facility or a visit with one of your other doctors before they can know if you are eligible or not.
Most of the time patients aren't spontaneously registering for your trial on a website or mailing in an application then waiting for weeks or months to find out if they are in or out. Most of the time it is the study staff spending a lot of time tracking down individuals who are on lists of possibly eligible people (like a cancer registry list or a list given to the study by a doctor or clinic), as well as hanging out in the clinic in case someone eligible comes in that day.
Like I said sometimes there is a delay between when you say yes you want to be in it and they have all the medical test results needed to confirm you are eligible. One study I was a guinea pig for took awhile because one medical test they wanted the results for was done at an outside clinic and not the main hospital and especially in the paper record days it took awhile for them to get the record sent as it wasn't needed immediately and the people with stat requests always go first when copying/ faxing/mailing
Thanks, KayMarie. It sounds like a one week delay in enrolling in a study would be commonplace, depending on details, so allowing a patient to skip the process on those grounds is unreasonable.
Can you blame people for being somewhat skeptical of the FDA, when stuff like the MelaFind debacle happens?
I don't think the FDA should relinquish any role in determining safety, although I think they should take a looser role in determining efficacy.
Are there not Federal laws (FDA) that would nullify or take precedent over these state measures? Certainly a company in New Jersey has no obligation to offer an investigational new drug to a Colorado citizen. These laws if they can be applied will only affect companies within the state borders but again I would think they would be superseded by federal law.
"State right-to-try laws have no power over the FDA, and nothing states can do can compel the FDA to abide by their right-to-try laws." Never mind. Should have read more carefully.
A Right to Try bill has been introduced into both the Senate and Assembly in NJ in June and referred to their respective Health, Human and Senior Services Committees.
I plan on writing some strongly worded letters. Future schedules for each committee have not been posted yet but in the case of the senate both sponsors are on the committee, one of whom is the chair, so I don't have high hopes.
It is fine line between encouraging innovation & letting dangerous products on to the market....
I'm sorry, but I'm not seeing a 'debacle' documented at the site you linked to. The device was narrowly approved, due to real concerns--principally the high rate of false positives which would result in unnecesary biopsies and the fact that it's not designed to detect large melanomas, colorless melanomas, and other types of skin cancer (such as basal and squamous cell carcinomas) all of which are detecatble by standard dermatoscope examination.
I think a very good lesson in Right To Try comes from the experience with AZT. It's a great case study in the difficulties faced by FDA to do their due diligence to ensure that a product is safe enough to release to the public while moving fast enough to keep good products from being unduly delayed.
The short story is this: word got out about a possible AIDS drug that was being studied, but had not yet completed clinical trials. AIDS patient advocacy groups became very vocal, pressuring FDA to allow this drug to be used immediately. The FDA ended up caving to pressure and approved AZT before trials were completed and adequate safety and dosing information was in. Lots of AIDS patients began taking the drug, and lots suffered very serious side effects. Over the following years, as more data came in, the dosing was adjusted down to the point that it was finally tolerable and still effective. The advocacy groups admitted that they were wrong to pressure for AZT's immediate approval and acknowledged that the FDA (surprise, surprise) was actually useful and not simply being obstructionist.
The switch from "terminal" to "advanced" is curious. The two are not only not interchangeable, but they don't mean the same thing at all. My husband is terminal, but not advanced - I.e. there is no cure for his cancer, and it will eventually kill him (unless one of the new drugs coming down the pike does the trick - he's in a phase 2 trial right now), but he's not advanced - he has a single known metastasis, which currently has little-to-no effect on his daily life or ability to function. Push comes to shove, his brother is sicker than he is - except for the fact that his brother can expect to live for about 30 more years, while his life expectancy is about 3-5 years.
Brett, I agree with JGC, that is kind of a non-story. Plus it was about detection, and there is an issue with misleading diagnostic tests.
Plus it has nothing to do with "right to try." What they want the "right to try" are experimental pharmaceuticals may not help, and could cause further harm... plus hamper real research into actual effective treatments. As noted by Todd W. and AZT.
More like "Right to Die" as opposed to "Right to Try"
Rob says "One point I’m missing….would the drug companies be required to provide the drugs…even if they are still unapproved and in short supply? Couldn’t companies just say they are not available? I’m not sure I’m seeing how this bill would transfer the drugs from clinical trials to “me to” patients."
Imagine you're an ethical pharmaCEO. A member of the public petitions you for access to an investigational drug per this type of law. Your company says 'no'. Good luck pleading restricted supply, safety concerns or anything else when the s*** hits the public relations fan. You may have no politically-digestible means to avoid releasing the drug for these cases. That is, while still a bad idea it becomes the lesser evil.
And the way the law is written, if said drug causes the person to die, there is no recourse for the family to sue.....
Good luck pleading restricted supply, safety concerns or anything else when the s*** hits the public relations fan.
In this scenario, you have a public relations firm available to fight fire with fire. Have them ask among your clinical patient trials for a few cases who would be willing to go public (privacy laws require this step). Point out that these patients, who unlike the petitioner were willing and able to play by FDA's rules, need the drug too, and because they are playing by the rules, they get priority. Everybody else can join the queue.
No, this is not going to persuade narcissistic libertarian kooks (pardon the redundancy). But normal people (who we hope are most of the population) will understand that limited resources must be distributed according to some rules, and as long as those rules are clear and fair, most people will accept the results.
Sounds like we are already seeing how that issue with supply plays out with the potential Ebola drugs. Sure we can let the companies give it out (and it isn't like we really can let them infect people with Ebola for clinical trials and who knows when the next outbreak will hit).
For a lot of these more unique compounds they are made by small start up type companies that don't have the resources to make huge vats of the stuff.
Of course the Ebola companies are damned if they do damned if they don't. If the give them only to Africans then we are just being colonial and using them for our own ends. If we give them to Americans we don't care about anyone but our own.
I can't agree with you on this one. Your primary argument is that the likelihood that an as-yet-unapproved drug will help a patient is small, and thus giving them access to those drugs is a "false hope". It seems to me that the patients would very likely know this, however, and are willing to gamble. You say that degrading the time they have left and emptying their bank accounts is a worse outcome -- but that's strictly a matter of opinion. And frankly, it smacks of paternalism. As long as all parties are going into this with their eyes open, they should be allowed to.
Your point about the FDA being federally run and thus not beholden to state law is certainly valid. But all that does is make me think that we need a federal right-to-try law.
(1) it seems from what I've read that giving the zMapp product to four people has exhausted the world supply of it; and
(2) the FDA didn't seem to have any problem with allowing it to be used.
But, more generally, it's one thing for physicians to prescribe approved drugs "off-label" for a condition for which they are not approved - the Kalley situation, as Orac notes - it's both legal and I understand widely accepted under appropriate circumstances; but it's quite another to take anything that's been through Phase 1 and remove all state-level restrictions on its prescription. It's an invitation to the Burzynskis of the world, and we surely don't need more of them.
The patients consent means little; these patients won't have their eyes wide open because the risks are UNKNOWN.
As far as the financial liability, many of these patients will also not likely realize the impact of what they are agreeing to. They are desperate and under tremendous emotional stress, and they rarely [probably never] take an attorney along with them to a clinic. These situations are not the same as applying for an adjustible rate mortgage.
In circumventing hospital review boards, this law removes the advocate for the patient. Not only are patients under great stress, they absolutely cannot do their due diligence because they have no data. The laboratory studies are proprietary.
It isn't paternalistic to require that a drug have an adequate safety profile, its responsible government.
Orac, except for the substitution of "advanced illness," the Michigan bill wording is the same as the final Colorado bill--you may have been looking at a version of the Co. bill before it was amended.
Perhaps Jann is the person to ask--is there any one who would have standing to challenge these laws and get them thrown out?
" it seems custom-made for drug companies, to make sure that they get their money for experimental therapies administered under “right-to-try,” no matter what, even letting them go after a deceased patient’s estate."
IMHO, the political-economy argument in Orac's post is right on the, er, money. At the beginning of the article I was thinking, 'yeah, this is bad science, but not that harmful, so maybe not a priority.' But then, as Orac unpacked the Libertarian Kool-Aid behind all this, I changed my mind. What we have here is pseudo-science performing it's typical economic function: letting greedhead scum fill their pockets with profits by sucking dry people facing pain and death. Except this is WORSE in an way than the lies of the NAM-scammers because it writes some very scary things into law, establishing precedent that can be more widely applied, and so on.
The recurring theme of my posts here is that the fight against pseudo-science will not be won by applying the methods of science. It's a political problem, a persuasion problem, and thus rhetorical strategy is key to the outcome. From the standpoint of rhetorical analysis, the question is not whether a given claim is true in any absolute sense, but how well it works in terms of the audience in question. The whole "SBMers are just shills for Big Pharma," schtick has a lot of purchase, for reasons that 'make sense' I shan't detail here. So when Orac makes statements like the one quoted above, the rhetorical value is immense, as they provide effective ammunition to counter an effective discursive tool used by the bad-guys. This ammo is all the more useful as the issue of profiteering is especially a concern to people who are more-or-less on-the-fence on some of these questions, and politics typically swing on whether and where the 'uncommited' may fall.
In short: Bravo, Orac! Good stuff.
This notion didn't exactly pan out for Chimerix.
For what it's worth, my Michigan House representative is on the Committee on Health Policy and was not one of the cosponsors of the legislation. I actually passed your writeup on the problems with right-to-try legislation along to one of his staffers, so if' we're lucky that might slow things down a bit.
Thanks. I'm under no illusions about our ability to stop this awful bill. As I morbidly joked in the post, to most people opposing this law is akin to advocating a law mandating puppy disembowelment. You're viewed as the killjoy, the cruel, insensitive guy so uncaring about real patients that he doesn't care that he's "taking hope away from dying patients," rather than as the person trying to protect dying patients from abuse. I spoke with one of the only people who testified against this bill when it went before the Senate health committee. He said the looks he got from supporters of the law were vicious.
That the bill will pass the Senate is already pretty much a foregone conclusion, particularly the way they're sneaking it through without any fanfare. (I still haven't seen any new news accounts since last month.) If it's going to be stopped, the House is where the stand will have to be made. My representative gave me a respectful hearing. He is a cosponsor of the House version, but it is clear to me from his comments that he really didn't know what he was signing on to, which is probably true of most of the cosponsors.
While there are surely issues with the bills, I personally disagree with the extreme opposition argued here. Clean data is good but too many people don't have an option to wait for clean data.
Most such patients would realize it's a 'hail Mary' situation but that's all they have. They don't have time to see scientific verification proceed at its necessarily measured pace.
People are entitled to take their own risks, especially when it's their life on the line. "I'm sorry, we are not ready to be sure this drug is safe enough for you" doesn't cut it. Waiting patiently for scientific rigor is not an option.
@Jay - and when these "untested" treatments start killing people - because we don't know proper dosing or all of the potential side-effects, what will you say then?
How about a potentially life-saving treatment that is rushed through (via this bill) and kills a bunch of people, but it turns out that if testing had been done, those effects could have been avoided (but now the drug is blacklisted in the public's mind, because of the first series of incidents).
Just because people can make an emotional appeal does not mean the government needs to be party to what may be, in effect, assisted-suicide.
I am the wife/caregiver of a terminally ill patient. My husband has stage IV lung cancer. For the most part, I disagree with your argument.
Assigning a big picture secret libertarian motive to the bill is no worse than CAM people insisting that 'Big Pharma doesn't want to find the cure so they can continue to make money on chemo." The intent of the bill is not a libertarian takeover, but rather a means to provide terminally ill patients access to medication that could help them extend their lives.
Your false hope argument is offensive for a couple of reasons. First of all terminally ill people aren't stupid. They are acutely aware of their limited time to be alive. Even though my husband had a complete response to chemo, we understand the cancer is lurking and will come back and kill him. False hope is for the rest of you who don't have to face your mortality. Have you made a will, bought cemetery plots, checked into your life insurance, bought a suit to be buried in, asked a friend to sing "Amazing Grace" at your funeral? Probably not. There's no denial or false hope here. That being said, we can't live our lives in death mode all the time. It's all about quality of life--and good news and hope improve quality of life. When you are terminally ill, the idea that something can extend your life is comforting. Thank God there's always someone like you ready and eager to pull that pillow out from under dying patients' heads. God forbid they may actually think there's hope.
The approval process takes too long. For example, Nivolumab, an immunotherapy drug, still isn't approved for use. Phase 3 trials are done and the results demonstrate that it works in a certain percentage of patients. It's still not available. I think it's finally been approved in Japan, but not here. The rumor mill predicts Nivolumab will be approved in late 2015. That's 160K LC deaths from now.
You argued allowing terminally ill patients access to meds isn't equitable due to wealth and other factors. I agree. But please remember that these same inequities already apply in the trial process. Although the medications are free, the trial process is only available to those who either live near a trial or can afford to travel to one. Also, certain hospitals participate in more trials and it's usually hospitals that accept a variety of insurances. If you're at an HMO that isn't at a comprehensive cancer center or University, chances are your doctor may not have access or knowledge of all available trials. People in most poor countries don't have access at all. Does that mean we should stop doing trials? Of course not. We shouldn't fight to exclude the wealthy, we should fight to include the poor.
Finally, people with certain preexisting conditions are precluded from participating in trials. Drug companies want their drugs to succeed (rightly) so they set very specific guidelines for whom can participate. If you have an autoimmune disease, you probably aren't going to be accepted into a trial. Loosening the noose around these restrictions would give access to potentially life extending drugs to those who were excluded from trials due to somewhat arbitrary guidelines. And unlike chemo, many of the new drugs have fewer side effects and therefore improve quality of life.
I don't disagree with you entirely. We need restrictions and guidelines. Perhaps Phase 1 is too early. Maybe we could up it to stage 2 and insist the decision to try a medication be made with the approval of a doctor.
The likelihood that this bill will allow someone to get access to a lifesaving drug is vanishingly small. The vast majority of drugs that go into clinical testing will never come to market, and of the ones that do only a tiny, tiny minority will be drugs capable of providing a cure to a terminally ill person. The majority of people who get access to a drug through this kind of legislation will end up wasting their time and money on drugs that, at best, do nothing and at worst make them sicker or even kill them sooner. This is why Orac calls it a cruel sham. The law should protect people from harm, not encourage it.
The reason why it's not been approved? Bristol Meyers hasn't yet submitted it to the FDA for approval. BM expects to do so later this quarter, which will still be months ahead of the predicted timeline. Hard to see how you can blame the regulatory process for a decision made by the company developing the drug.
I'll also note that Merck's pembrolizumab, a competing anti PD-1 antibody, is about 8 months ahead of Nivolumab in teh approval process, so it's not like Nivolumab is the only game in town.
Does this mean I can dust off the drugs we've thrown in the trash the last 20 years, open phase II's on them that I secretly plan to recruit 1 patient per year (at most) for, and start pushing them on patients at astronomical prices and without any risk to myself. Will it make a garden where a thousand Burzynskis can bloom?
How about if my friends open the phase II more than 100 miles away - I forgot about that part.
I’m terribly sorry for you and your husband. Lest you think I don’t have any personal experience with this sort of situation, my wife quit her job just under six years ago to take care of her mother, who was dying with stage IV breast cancer, complete with liver, lung, bone, skin, and brain metastases. She observed first hand on a daily basis what happened, and I observed less frequently (but as frequently as I could) because my wife actually moved in with her mother for a few months to do this. It was not an easy time for either of us. So I am not entirely unfamiliar with the personal issues you bring up, although fortunately not (yet) personally or with my wife.
That being said, it is not a “conspiracy theory.” As someone who is knowledgeable about the “health freedom” movement, I recognize in the Goldwater Institute a lot of the same code words that are more about neutering the FDA and allowing the free market to determine what drugs are sold, particularly the part where they discuss having the FDA only assure safety and not efficacy (the Kefauver-Harris Amendments). The arguments made by the Goldwater Institute are also riddled with misrepresentations of the clinical trial process, the law, and the likelihood that patients will be helped by drugs administered off of clinical trial. Note that all of the current right-to-try laws and all of the right-to-try bills being considered by legislatures (such as in Michigan and New Jersey) were written, sometimes word-for-word, from a template produced by the Goldwater Institute. Certainly, the Michigan and Colorado laws are, with only slight variations. Also, if the Goldwater Institute isn’t such a driving force, why is it that it’s flying its representatives to every state legislature considering such bills to testify in their favor. That’s what happened in Michigan.
My analysis of the situation, taken in context with my long time study of “health freedom” advocates, leads me to conclude that the Goldwater Institute and “health freedom” advocates are using terminally ill patients to further their antigovernment agenda, holding out the false hope of “right to try” laws out to attract terminally ill patients to endorse it and to portray opponents who point out that there’s nothing in such bills that is likely to help terminally ill patients as cruel, cold, uncaring monsters who want to deny hope to the terminally ill. Certainly, I’ve been portrayed that way on Twitter by a Missouri right-to-try advocate and by Christine Sandefur of the Goldwater Institute herself. Nothing could be further from the truth. It is because I don’t want to see such patients taken advantage of that I do what I do, even as I know I’m likely to be attacked, perhaps viciously, in social media and elsewhere, for bringing a science-based, rather than Goldwater Institute misinformation-based view to the issue. A particularly good example of Goldwater Institute misinformation is its claim that only drugs “deemed safe” by the FDA would be eligible. Sorry, Ms. Sandefur. Phase I is not an adequate standard for “safety,” even for terminally ill patients, for the reasons I explained in the post.
No one said that terminally ill people are stupid, least of all me.
Whether you realize it or not, you have just very eloquently described why even the most rational and intelligent person who is terminally ill can still be very much prone to pitches that provide false hope, like right-to-try. As I said in this very post, I can’t even 100% guarantee that I wouldn’t be tempted by such a hope if I were to be diagnosed with a terminal illness. I would hope, however, that someone with a more objective perspective would try to stop me, if it were ever to come to that.
I’m aware of the issues with clinical trials, working, as I have, in two different NCI-designated comprehensive cancer centers for my entire post-training career. Several years ago, when I worked in NJ, it was a big deal that the state came to an agreement with insurers that they would pay for clinical trial care. I would also agree that access to clinical trials should be expanded. Here’s the difference. Given our limited resources, where should we as a society spend our money? On expanding access to clinical trials that are likely to produce generalizable knowledge validating new treatments? Or on using untested, potentially dangerous drugs in a far less controlled manner, in a way that is likely to be very expensive and even less likely to help patients than the most longshot clinical trial? Expand access to clinical trials, yes. Right-to-try is the wrong way to go about it, particularly given the hidden agenda to weaken the FDA that is clearly part of the reason for these right-to-try bills and the observation that such programs are far more likely to harm patients than to help.
Finally, there already is an expanded access program. We can discuss whether it’s too difficult (and, yes, the paperwork load is onerous for a doctor who wants to put a patient on an investigational drug through expanded access), although it is rare for an expanded access request to be turned down by the FDA if the company is willing. If there is to be reform, that is where it should be, not in state right-to-try laws, which will only serve to make such issues even more difficult to resolve than they are. It also needs to be understood that clinical trials are always an uneasy tug of war between scientific rigor and ethics. We want to include as many patients as possible, but being too liberal often decreases the odds that a meaningful result will come out of the trial. It’s a question clinical trialists wrestle with every time they design a clinical trial. There’s a reason why I called right-to-try laws “placebo” laws. They don’t actually do much of anything (other than confuse things) but make legislators feel good that they think they’ve done something to help the terminally ill.
The answer is yes, as far as I've been able to ascertain. Right-to-try basically legalizes that. Its only requirements are that the drug has to have passed phase I and still be in clinical trials. However, you might run afoul of the FDA. That shouldn't be a major concern, though, as we all know from the history of the FDA's dealings with Burzynski. You could certainly get away with it for a decade at least before the FDA makes even a half-hearted attempt to shut you down. And you could go after the estates of your victims patients to collect. The Michigan bill explicitly allows that. You and any doctor helping you couldn't be sued, either.
Its basically a license to print money on the backs of terminally-ill patients....
The reason why it’s not been approved? Bristol Meyers hasn’t yet submitted it to the FDA for approval. BM expects to do so later this quarter, which will still be months ahead of the predicted timeline. Hard to see how you can blame the regulatory process for a decision made by the company developing the drug.
I’ll also note that Merck’s pembrolizumab, a competing anti PD-1 antibody, is about 8 months ahead of Nivolumab in teh approval process, so it’s not like Nivolumab is the only game in town.
There's no game in town right now. They aren't available. That's the big point and the unfortunate truth. Why hasn't BM submitted their data for approval? I don't want to believe it's for financial reasons. I don't buy the 'big pharma' crap for a second, but something is keeping it from being released. What is it? And whether or not it's Merck or BM, doesn't matter. There are drugs that can extend the life of certain lung cancer patients (160K dead a year) but for whatever reason, be it bureaucratic red tape or corporate sludginess, they aren't available. Lung cancer, the deadliest cancer, is one of the least funded due to stigma. Lung cancer patients rely on gains made for more "deserving" cancer. Sad but true.
I apologize if my comments came across as a slight to the FDA. That wasn't the intention. My intention was to highlight how there are effective drugs that aren't available to people.
You're missing my points, perhaps deliberately.
First, as Bristol meyers has not yet applied to the FDA for approval of Nivolumab, I don't see how one can reasonably argue its failure to have reached the market is a function of a failed approval process.
Second, Nivolumab is is not the only anti PD-1 antibody in development and on track toward approval. At least one other that I'm aware of is also in development and is actually several months ahead in the approval process.
Nivolumab is also not unique in targeting the PI 3 Kinase
T-cell activation pathway: FDA approved Yervoy (Ipilimumab), an anti CTLA-4 antibody, targets the same pathway.
While I agree it would be great if the Nivolumab had demonstrated safety and efficacy and was aready approved, I don't see how the approval process is to balme for its failure to already be approved.
You say that the approval process takes too long: how exactly would you change it to reduce the time required< while still ensuring tht potential new drugs demonstrated sufficiently that they were both safe and efficacious?
The approval process always takes time - whether it be one week or several months....time is time.
If the drug is approved on Tuesday, then people will have died on Monday waiting for it - you're never going to satisfy everyone.
I got your point. Did you read my response? My point is this: It doesn't matter why it takes so long, whether it's due to "bureaucratic red tape or corporate sludginess". I'm not looking to blame anyone or anything only to inspire change. The point is that life-saving or life-extending drugs exist but are not available. There's a lengthy space of time after a medication is proven effective until it actually hits the market. In the case of Nivolumab, we're talking a couple of years. Considering the median survival for lung cancer with treatment is 8 months, that's too long, whatever the reason. There should be a way to make the meds available in that space between. (actually there is, but it's very limited)
As for Yervoy, last I read it was in clinical trials for NSCLC and not fda approved for anything other than melanoma.
Believe it or not, these drugs, at this point most likely won't help my situation. My dh is a chemo-responder and I've spent most of the summer enjoying the hell out of his company. :) Chemo responders are LESS likely to respond to immunotherapy. I'm hoping future research shows why.
And finally, I am not asking for false hope, but actual real hope. Immunotherapy drugs have evidence behind them. They aren't Gerson or homeopathy or chiropractors, which are sadly (ironically?) easily available and not restricted by law.
"That being said, it is not a “conspiracy theory.” As someone who is knowledgeable about the “health freedom” movement, I recognize in the Goldwater Institute a lot of the same code words that are more about neutering the FDA and allowing the free market to determine what drugs are sold, particularly the part where they discuss having the FDA only assure safety and not efficacy (the Kefauver-Harris Amendments)."
I have to give you this point. I don't know enough about it. For my demographic, it's not about politics. It's about access.
When Joe was first diagnosed with cancer I was repeatedly given two bits of really bad medical advice. The first was to banish all sugar from his diet. The second was to consider not "poisoning" Joe's body with chemo. I researched both issues and discovered the sugar advice was unfounded but basically harmless. For the chemo issue I found this article: http://scienceblogs.com/insolence/2009/05/20/chemotherapy-versus-death-… And from then on, your blog became one of the voices I counted on with " a more objective perspective". I totally appreciate your blog for this reason. Anytime I hear about a new treatment, I look it up on your blog.
However, I believe that making access easier to SOME drugs could extend the lives of many nsclc stage iv patients. (and probably other patients I don't know anything about). It's not false hope if they actually work. If the bill is bad, can it be rewritten so it makes sense?
<blockquote. I’m not looking to blame anyone or anything only to inspire change.
Inspire what type of change, however--what changes do you believe could be enacted that would accelerate drug approval without compromising safety and ensuring efficacy with respect to identified indications?
I’d argue that until the developer has submitted all required documents to the FDA, detailing all results from all pre-clinical and Phase I, II and III clinical trials, and the FDA has the time to not only perform an independent audit and review of the evidence but also to respond the developer and request additional information or direct additional studies be completed, and they finally actually approve the drug for sale, it hasn’t been proven safe and effective.
If the basis for concluding that it’s too long is that people who might be saved if it were available now will not survive, surely any regulatory process that goes beyond a simple rubber-stamp procedure must be considered ‘too long’.
I cannot at this point think of changes to the regulatory system that would have shortened the approval process with respect to Novimulab. Bristol Meyers cannot submit the drug for approval until they’ve prepared and validated their documents (a long, detailed and highly technical undertaking) and the study was completed quite recently (results were announced in June 2014). The FDA certainly can’t act until they receive the completed submission package. It seems to me both BM and the FDA are moving with all appropriate haste (and, it’s important to recall, are actually months ahead of schedule.)
The Phase III clinical trial showing Novimulab to be effective was also with respect to melanoma, and if approved at this time it also would be approved only for melanoma.
There probably are some who may be helped by the few drugs that are well into phase III so we may have enough data to know if there is more hope than false hope.
Unfortunately that isn't the way the people pushing for these bills want and sadly in today's political climate I don't think we can get a common sense bill.
It is either going to be all or none, and all is really bad, especially when we don't yet know with much certainty what kind of dosing regime may be effective and safe enough you don't cause way too much damage to the person. While we try to make drugs specific to tumors, you usually kill some healthy cells along the way and not knowing at all what kind of dose may be effective (just what didn't kill a dozen or so healthy people) it is really scary.
Especially with way too many doctors promising cures with inappropriately dosed drugs along with the woo they peddle. Give them access to a much bigger range of drugs, it may hurt a lot more people than it helps.
A few drugs, under pretty tightly controlled conditions may be OK, but the free for all the bills being written are...and the people supporting those bills are not likely to support something reasonable. The reason the bill isn't reasonable now is they don't want something scientifically rational and reasonable and will fight against that tooth and nail, IMO.
Maybe I should clarify. The fda approval process is only too long for people with terminal diseases. We don't need to alter the fda approval process. It's important that data is reviewed and scrutinized. However, we need to find exceptions for terminally ill patients to access drugs that aren't yet on the market but have been proven effective. That's the change that needs to be made. I understand there needs to be very, very specific guidelines. We have something in place now called compassionate use but it is so limited.
As to the "can't win, don't try argument'. That's a terrible argument. The goal in medicine should be to heal. Obviously, you can't save everyone (or anyone for that matter), but the goal is to heal as many as possible. The fact that some people die waiting for medication is an outcome we can change. Procedural improvements are made all the time to improve outcome. That's the whole point of medical science, isn't it? Could you imagine if a doctor said, "Well, no matter how successful bypass surgery is, people will still continue to die from clogged arteries. Therefore we shouldn't do bypass surgery." It sounds ridiculous. Do want to have a doctor who says, "Wear gloves? Why? No matter what I do, I can't stop every infection so why should I wear gloves?" There are a million ways procedural changes have improved outcomes in medicine.
Right now (expecially now with this the immunotherapy ball is really rolling) we can make a change that will improve the outcome for stage iv lung cancer patients. I believe we should find a way to make that change. I agree with Orec that this bill oversteps. While it might improve some people's lives, it could potentially cause great harm to others. However, let's not throw out the baby with the bathwater. If the crazy libertarians have a bill, counter it with something better.
Why can't there be a two-step approval process? Step 1 patients wait for the drug. Step 2 patients can receive a drug that has finished phase 3 trials (or phase 2 if the results are phenomenal) and is expected to be approved. Approval would be subject to dx and other conditions. (2 failed lines of chemo, supervision of board certified oncologist, release of responsiblity, etc... whatever it needs to be.) All this would do is make compassionate use more universal and it would allow drug companies to get paid for the drug prior to it's general release.
Well, there is no correct way to address this legislation that would be applicable to any / all circumstances. But, for one company that is backing this bill is Neuralstem, and if you had Lou Gehrig's disease, what choice would you have ?
Neuralstems answer is repair unhealthy or dying cells, with healthy cells, similar to what most anyone would do if they needed an organ transplant. The body understands cells, more so than it would understand most drugs. If they have passed Phase One for safety, are showing efficacy in PHASE TWO, then why should an ALS terminally ill patient wait ?
Neuralstem, as many companies emerging in the Regenerative Medicine sector are the tip of the arrow as the science progresses. Advanced Cell Technology, and their CSO Robert Lanza are sandbagging years worth of data, that will absolutely astound the medical community. With their Hemangioblast Derived Mesenchymal Cells, they have eliminated Multiple Sclerosis in animal models in six days, with just one injection. ACTC has stated these MSC's are applicable to over 100 different Auto-Immune disorders.
So, based on what vantage point you choose to see on the horizon, at least for ALS, THE Right To Try bill is Right On.