Tuesday, November 18, 2014

An Open Letter to State Congress Members on Right to Try Laws

Dear Members of Congress,

"Right to try" laws, that is, laws designed to purportedly make it easier for terminally ill patients to gain access to unapproved, experimental drugs, have been in the news quite a bit recently. Several state legislatures have overwhelmingly supported these types of bills, with little or no opposition, let alone serious, critical examination. Although advocates of these laws claim to have the rights and interests of terminal patients in mind, much of the legislation, and the long-term consequences, are likely to do more to benefit unscrupulous companies and hucksters while doing little to help, or even increasing the harm to, patients in great need, not to mention legitimate companies.

The driving premise behind right to try laws is that terminally ill patients have nothing to lose by trying unproven treatments, and that they ought to have the right to gain access to those treatments without undue burden. A dominant view among right to try proponents is that the Food and Drug Administration, and the various regulations they enforce, create inappropriate barriers to the timely release of potentially life-saving drugs. Advocates believe that earlier access will save lives, coupled with the belief that the government should not interfere with a patient's right to decide what treatments they wish to pursue.

While right to try laws seem, on their surface, to do nothing but benefit patients, they will very likely fail to do so, and perhaps even harm patients, for a number of reasons.

First, and perhaps most pertinent to the passage of state laws, they are likely to come into conflict with federal law. In cases where federal and state law conflict, federal law will trump state law. What this means for "right to try" is that there will be no real change for patients. The laws would do little more than make people feel like they are changing things, that there is now more hope for the terminally ill. It is an empty promise. Of course, this depends upon FDA enforcing federal regulations. They may opt to let cases slide, in which case advocates get what they want and patients gain access to experimental treatments. Or, FDA may crack down and demand compliance with federal regulations. In those situations, patients, whose hopes had been raised by the state laws, will have their hopes dashed. In short, the state laws create a false hope in a very cruel fashion. And the legislators who pass these laws will be the ones responsible for this cruel bait-and-switch.

However, as much as the false hope argument is attacked by "right to try" proponents, it's a relatively minor, if emotionally powerful, drawback of these laws. Greater is the potential for harm in several forms. The most obvious is that the experimental drugs will directly harm the patients who turn to them in the hope of improving their lot. Thus far, right to try laws have limited their scope to products that have passed phase 1 clinical trials and are currently in phase 2 trials. While the phase 1 trial does provide some safety data, the picture is extremely limited, since phase 1 trials are quite small, and the results not generalizable to a larger population. There generally is no data on whether or not the drug will even be effective in humans at the end of phase 1; that is the purpose of phases 2 and 3. Of all drugs that pass phase 1 trials, only about one fifth continue on to phase 3. Of the other 4/5 that fail, half fail in phase 2 due to lack of efficacy, about 30% fail for strategic reasons (e.g., they are no different than existing treatments) and nearly 20% fail due to safety problems. Although proponents of these laws say that terminally ill patients "have nothing to lose" by trying an unapproved drug, there is a significant chance that the drug will kill them prematurely or significantly decrease their quality of life for the time that they have left, without any added benefit.

Taking on that risk of harm is one thing. But what of the pediatric patient? A child, in the best of circumstances, is not capable of making a choice to take an experimental drug, let alone when they have a terminal illness. Their parents are in little better position. No one wants to lose a child, and it is a rare parent, indeed, who would stop at nothing protect their child. But that emotion can cloud one's judgment. Though the siren call of a potential cure is alluring, chasing after it may not be in the child's best interest. More likely than not, an experimental drug will provide no benefit, but it will have side effects. Rather than making their child's remaining time more comfortable, desperate parents would waste their money on drugs that are liable to decrease their son's or daughter's quality of life.

The financial burden is yet another failure of these laws. While provisions are included to "allow" manufacturers to provide the experimental drugs for free, they are not required to do so. Likewise, insurers are allowed to cover the costs, but they can also refuse to pay. This leaves the patient to foot the bill. Considering the costs associated with developing a new drug, particularly where successful approval is no guarantee, that bill will be more than most families can afford. The model legislation from the Goldwater Institute and the laws that have passed so far have all failed to include any provisions to assist patients and their families with the costs of experimental drugs accessed outside the FDA's existing compassionate use framework. Unlike federal laws governing charging for experimental drugs, the state laws have no oversight or approval process for whether a sponsor or manufacturer can charge the patient for the drug, nor do they contain any limits on how much can be charged. Although cost considerations are still an issue under the federal expanded access program, state right to try laws make access even less favorable for terminally ill patients. To quote bioethicist Arthur Caplan, "right to try" laws should more properly be called "right-to-beg" laws.

However, the costs associated with getting access to experimental drugs under state right to try laws are not the only financial burdens patients and their families will face. In those cases where the experimental drug leads to harm, most of these laws leave the patient without any support. Thus far, right to try laws exempt insurers from paying for any care required consequent to using an experimental drug. Just as the patient is left paying for the drug in the first place, they are also left footing the bill should the drug cause any new medical issues. Facing a terminal illness is difficult enough without worrying about how to pay for both the drug and the problems it creates.

In addition to placing increased burdens on patients who opt to pursue experimental drugs under these state laws, the right to try laws ensure a lack of accountability. State medical boards are barred from taking regulatory action against the licenses of physicians who recommend or prescribe these experimental drugs. Even if a patient is unlikely to benefit, or may even suffer harm, from an experimental drug, these physicians can continue to practice. Some laws, such as Louisiana's RS 40:1300.381-386, not only prohibit medical board actions, but go so far as to bar civil litigation, meaning that patients lose the option to sue the physician for malpractice. This creates an atmosphere ripe for predatory quacks who need not fear retaliation.

Other state laws, like Missouri's RS 191.480, limit liability against the manufacturer to gross negligence or willful misconduct. This means that patients would need to prove that manufacturers were knowingly careless about patient safety. Even in those states where there are no explicit limitations on the patient's legal right to redress from the manufacturer, nothing in the laws prohibits manufacturers from requiring the patient to sign a contract that limits liability. These bills are not patient friendly.

Manufacturers, likewise, take a dim view of state right to try measures. Liability is a significant disincentive for companies. While nothing in the laws expressly prohibits manufacturers from using contracts to protect themselves, ironclad waivers of liability would likely fail if tested in court. Such contracts may be seen as coercive, thereby interfering with free and informed consent. Even worse from the manufacturers' point of view, while the laws do not create a cause of action, some, like Colorado's RS 25-45, may create a cause of action if the manufacturer did not act in "good faith" (undefined) or was negligent. Furthermore, no statute of limitations is placed on such actions.

Right to try laws put manufacturers in a difficult place publicly, as well as legally. As mentioned, the state laws give patients a false hope that can fuel activism. Given the legal atmosphere these laws create for manufacturers, they are unlikely to want to provide access to experimental drugs to patients requesting them. Fueled by hope, it is not a stretch to imagine particularly motivated patients or their families using public relations efforts to strong-arm manufacturers into compliance with their demands. Manufacturers ultimately want to do what is best in an economic sense. Denying access to a drug may be necessary to ensure it continues in the pipeline toward approval, after which it may help thousands of other patients and bring profits in to the company, while allowing access may jeopardize that process. On the other hand, negative publicity generated by patients and their supporters may lead to decreased sales and stock values, while providing access under state laws may run into problems with federal regulations.

That public relations position is particularly bad for a smaller company. Small companies generally do not have the personnel to handle the paperwork and other regulatory burdens of providing drugs through a "right to try" or compassionate use avenue. Similarly, their store of the experimental drug is limited to what is needed for their clinical trials. Providing the drug would therefore jeopardize their clinical trials, delaying or even preventing the drug from becoming available to everyone who needs it. Advocates argue that delays caused by FDA regulations ultimately kill thousands who, if only they had access to the drug, would otherwise have survived. Yet these laws may end in the very result they are trying to avoid: the death of thousands who otherwise would have benefited had the drug made it to approval.

Do small companies risk their clinical trials when faced with a PR campaign by advocates? Or do they deny access and risk a reputation of being "the bad guy"? Should they give in to well-meaning, but misguided pressure, what happens if the drug fails or even causes great harm that would have been avoided in the context of a clinical trial? Where a large company has the resources and other product lines to get through the media fallout, a small company just starting out would likely fail. Even if they managed to stay afloat long enough to get the drug approved, people would be scared to use it, not keeping in mind the difference between an early formulation with limited safety and efficacy data and the final, approved product.

Ultimately, state right to try laws create false hope for patients, but provide no real help to them. They do not help patients pay for access to the drugs nor for any adverse reactions caused by the drug. The experimental drugs most likely will provide no benefit at all, but will increase the risk of adverse reactions that can decrease the patient's quality of life. Other than informed consent requirements, these laws provide no other oversight to ensure the protection of the patients. There are no protections for patients in the event of injury or death, and their ability to seek compensation through legal means is often limited. Furthermore, the laws protect physicians from being held accountable.

Drug manufacturers are place in a difficult position, as well. The laws create a patchwork of differing regulatory requirements from state to state and, in most cases, protect physicians while placing most of the liability on the companies. The legal and public relations landscapes created by these laws are unfavorably to a company that is legitimately trying to get a product to market. State right to try laws are even worse for smaller start-up companies, whose future (and the futures of their employees) rests upon the success or failure of their product.

Although federal compassionate use regulations certainly have room for improvement, the answer is not to be found in state regulations, particularly those as poorly crafted as have already been passed. Those who support state right to try laws mean well, but they are, unfortunately, misguided. The main aim of these laws, led by the Goldwater Institute and their model legislation, appears to be the gutting of FDA regulatory authority, which has been built over the years to protect patients and consumers. This can only benefit quacks and purveyors of snake oil (see, for example, Stanislaw Burzynski). In the end, it is the patients who will pay the price.
______________________________
References:
Laws Passed to Date
Arizona Right to Try Law - RS 36-111 - Terminal Patients' Right to Try Act
Colorado Right to Try Law - RS 25-45 - Access to Treatments for Terminally Ill Patients
Louisiana Right to Try Law - RS 40:1300.381-386 - Access to Treatments for Terminally Ill Patients
Michigan Right to Try Law - 2014-PA-0345 - Right to Try Act
Missouri Right to Try Law -  RS 191.480 - Allows physicians to prescribe certain investigational drugs, biological products, or devices to certain eligible terminally ill patients

Opinions
Arizona Bioindustry Association - HCR 2005 – “Right to Try” Won’t Benefit Patients
Arizona Medical Association - Proposition 303: ArMA Board of Directors issues Statement of Concern
Drug and Device Law - On "Right to Try" Legislation
Medscape - Why 'Right-to-Try' Laws Won't Help Desperately Ill Patients
Dr. Eric Meyer - Proposition 303
JAMA Internal Medicine - The Strange Allure of State "Right to Try" Laws
Kaiser Health News - Laws Spreading That Allow Terminal Patients Access To Experimental Drugs
NBC News - Bioethicist: 'Right to Try' Law More Cruel Than Compassionate
Pharmaceutical Research and Medical Manufacturers of America - State “Right-to-Try” Legislation, While Well-Intentioned, Is Unlikely to Achieve Goal of Bringing Safe and Effective New Medicines to Patients
Science-Based Medicine - “Right to try” laws and Dallas Buyers’ Club: Great movie, terrible for patients and terrible policy
Science-Based Medicine - The illusions of "right to try" laws
Science-Based Medicine - Using the fear of Ebola to promote the placebo legislation that is “right to try”

4 comments:

  1. Wow. Very thorough and informative. I didn't know some of this stuff. We talked about this in an ethics class and also concluded that "some hope" is really false hope, especially when stuff has not been tried and when terminally ill patients are beyond the point of no return in their illness.

    Silly humans, right?

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  2. Excellent post. I've been in this world for a long time -- during which federal drug laws and regulations have been significantly liberalized to enable considerably more "compassionate use" of experimental drugs (that is, for individual patients who have no other options). There is a major can of worms that opens if those with a terminal illness can all just try anything, as your post suggests: do you allow the drug company to charge for the drugs? If so, what is their incentive to get their testing completed? If not, why would they want to make their generally small supply of drug (in production just for clinical trials) broadly available? Plus, if there are bad outcomes during this non-clinical-trial use, there are risks to ultimate approval -- even though the use isn't subject to the kinds of "controls" in controlled clinical studies, and the bad outcome could have arisen because of a unique characteristic of the particular patient. The liberalization of access happened during and around the AIDS crisis. Was it beneficial? I'm not sure a complete and scientifically valid history has been written. At that time FDA started allowing drugs to be approved on the basis of their impact on a "surrogate" endpoint (one that seems to point to ultimate efficacy). At least one drug caused excitement because it kept patients' T-cell counts from dropping (which seemed predictive of efficacy for AIDS). But it turned out patients died just as quickly. Drug approval issues are VERY VERY complicated. When we're dying we only want to try-anything. If you are very conservative about drug approval, you may harm people now (from lack of the drug) but protect people later (from harms CAUSED by drugs approved too quickly). There is no perfect solution. NONE. But if we let-anyone-take-anything we will never have the SCIENTIFIC evidence to support efficacy conclusions. (Irony to ponder: drug companies had been screaming for years and years that FDA was too conservative, but government held fast. Things liberalized during the AIDS crisis when patients were screaming FDA was too conservative. Those Big Bad Drug Companies were laughing all the way to the bank after sympathetic others took on their cause: which of course for them was about profit ...)

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  3. Not sure why I'm 8a4a2322-70e9-11e4-85b3-87a202d97343?? Trying this again.

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    Replies
    1. Hi. I'm not all that familiar with OpenID. You might want to check to see if there is a "Nickname" or "Username" field that you can edit.

      Delete

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