An unwarranted expansion of expanded access to investigational drugs

An unwarranted expansion of expanded access to investigational drugs

In the US, drugs (and medical devices) must go through a rigorous FDA-monitored procedure of safety and effectiveness testing via clinical trials before they can be marketed.   Some patients with serious or life-threatening diseases can access drugs not yet approved, referred to as "investigational drugs."  This is known as  "expanded access" or, colloquially, as "compassionate access."  Access is carefully controlled and there are a number of safety features in place to ensure proper use.  For example,  each expanded access request must be approved by an Institutional Review Board, a special committee designed to insure the protection of a patient's rights and safety, including a requirement that the patient is aware of all risks. A physician must determine that there is no comparable alternative treatment available and that the probable risk from the investigational drug is not greater than the probable risk presented by the disease.  The FDA must decide whether there is sufficient evidence of safety and effectiveness based on a particular patient's medical history, which provided by the patient's physician.  

Society's interest in access to a supply of safe and effective drugs is protected as well.  Access will not be granted if it will interfere with clinical trials of the drug.  And, if access is granted, there is follow up so that the drug's effect on the patient can inform the it's use in other patients.

But expanded access is limited access.  Some patients will be turned away.  This has led to attempts in the state legislatures and Congress to expand access even further, even at the risk of the process becoming so porous that expanded access threatens to become a crowd-pleaser (or, perhaps more accurately, vote getter) rather than a sober analysis of whether a particular investigational drug might benefit a particular patient and ensuring that it does not do so at the expense of the rest of us. 


Expanded access bills are currently pending in several states. (Both David Gorksi and I blogged about these over on SBM.) These are not really much of a threat, as the FDA has, for all practical purposes, exclusive jurisdiction over the drug approval process.  The bills allow terminal patients access to investigational drugs that have successfully completed a Phase I clinical trial as long as the patient has "considered" other options.  A physician must either "recommend" or prescribe the drug but cannot be disciplined by the state medical board for doing so.  There is no liability protection for the physician though, nor for the drug manufacturer.   The patient must give an undefined "informed consent."  But after the physician makes his recommendation, the patient is left to his fate.  There is no follow-up required, no reporting of results (or lack thereof).  If anything is determined that might assist other patients or the drug approval process, no one will know. 

The one certain outcome from these bills, if they become law,  is that the FDA will step in, lawyers in tow. It will try to prevent any manufacturer from providing access to a drug still in the clinical trial process.  Litigation will ensue, with the state's Attorney General shouldering the unenviable burden of showing up in federal court to defend a constitutionally-indefensible law.  All at taxpayer expense. And the FDA will win, as it should. 

House Bill 4475, introduced in Congress on April 10, is more troubling.  As Dr. Gorksi pointed out in his SBM post on the bill,  Congress has the power to greatly weaken the FDA's oversight in expanded access cases, and that is just what this bill would do.  

The bill requires the FDA to step aside when expanded access is requested by a "terminally ill" (a term not defined) patient who wants access to a drug that has not yet been approved by the FDA as long as it "is or has been the subject of one or more clinical trials."  In other words, a drug could have been rejected after Phase I, the very earliest clinical trial stage, where efficacy is not even a consideration and only rudimentary information on safety has been assessed.  

To obtain access, the patient's "licensed physician" must have informed him that there is no drug available likely to "cure" the illness.   Note, however, that the drug the patient wants to try doesn't have to "cure" or even make claim that it is a "cure."  All the patient has to do is sign an informed consent indicating that he knows "the known and potential risks" and whether there are any lawfully marketed drugs or other treatments for his illness. For some of these investigational drugs, meaningful informed consent isn't even possible, because the risk and benefits aren't really known.  Who is a "licensed physician" is presumably defined by state law.  Thus, in states where naturopaths are licensed and have prescription privileges, they will suffice.  

But we haven't even gotten to the worst part yet, and here I'll add my lawyer's two cents to Dr. Gorksi's medical view.  Unless there is willfull conduct or gross negligence involved, all is forgiven for the physician and manufacturer. "Wilful misconduct" means that the action was intentional.  Gross negligence means that one's actions so disregarded the safety of others that they are the legal equivalent of intentional.  In civil law, either would support the imposition of punative damages. In criminal law, either is sufficient to support a conviction for certain crimes. (For example, gross negligence can be sufficient for an involuntary manslaughter conviction.) So, basically, unlike medical malpractice product liability actions, no patient or his family would ever be able to sue for ordinary negligence. 

Bad enough. But it gets worse.  Not only is there no follow up, the FDA is specifically forbidden from requiring disclosure, collection or follow up of any information on the delivery the drug or clinical outcomes.  Thus, even if there is willful misconduct or gross negligence, who is going to know?  What record could one produce as evidence if no record is required?

So if you are a quack or simply lack any regard for the suffering of others, or both, here's a business plan for you:  Lobby for this bill.  If it's passed, develop a sketchy drug and  flunk out after a Phase I clinical trial.  Get a network of fringe doctors (perhaps including naturopaths) to sell desperately ill patients on the idea that  the drug will . . . what?  Well, there's no requirement in this bill that the drug have any evidence that it helps the patient, so you must be vague here. Sell the drug to patients and get your cash up front because your customer, I mean patient, could die before you collect. Legal tip:  You do not want to be a creditor in probate because there may not be enough money to pay you.  And if your customers, I mean patients, die an agonizing death after taking your drug, all is forgiven.  Or, at least, there won't be any record.  And legally, that's the same thing, right?

Points of Interest: 4/27/2014
Points of Interest: 04/26/2014