Time on fire

Dying patients can’t get new drugs that could save their lives

Norman J. Scherzer
LRG Executive Director

In the past few months we have lost several Life Raft Group members who were not successful in obtaining drugs that were available for clinical trials. Two stories in particular stand out. Both patients are Canadians.

The first patient’s GIST was resistant to Gleevec and to Pfizer’s SU11248. He tried to get into a phase I clinical trial in Boston for a new drug, BMS354825, but was told that there were no available slots. With assistance from the Life Raft Group, he turned to a clinical trial in Scotland. While in the process  of joining the trial — the drug was not available on a compassionate use basis — he ran out of time.
He died the day he was supposed to be in Scotland to see a doctor about starting the trial.

The second patient’s GIST was resistant to Gleevec and so he participated in the phase II clinical trial for SU11248. Believing that he was experiencing unacceptable side effects from the drug, he voluntarily left the trial. Later he discovered that he had been on the placebo. The “side effects” were likely symptoms of his cancer. But because he voluntarily left the trial, he could not rejoin it in order to get the actual drug.

The Life Raft Group tried to get the drug company to provide him with SU11248 on a compassionate use basis (the drug was available on such a basis in Boston but not Canada) but again time ran out and the patient died. His wife had died of cancer two years earlier, so their 9-yearold son was left an orphan.

In the latter case, there were two hurdles the patient and the Life Raft Group failed to navigate quickly enough: first, getting the drug company to make the drug available on a compassionate use basis and, secondly, getting the local hospital’s institutional review board to approve this. The fact that this had been done by another IRB at a major hospital in the United States did not matter.

One could only imagine what would have happened if these patients had a deadly communicable disease. Picture this scenario: Two patients are dying from anthrax. A reporter discovers that there is a drug that might help save them. But both patients die before they are granted access to this drug.

The reporter also discovers that a committee of medical experts at the local hospital took three months to decide if the patients should get this drug. This institutional review board met only monthly and its top priorities were protecting patients against unsafe treatments and, of course, protecting the institution against lawsuits. The reporter also learns that these experts refused to accept the findings of another expert committee at another prestigious institution, but instead had to duplicate the process.

Imagine the fallout from the ensuing story. Politicians would decry the lack of urgency and inflexibility of the medical bureaucracy, and the absurdity of trying to protect a dying patient from a potentially unsafe treatment.

Protecting a dying patient. Now that is an interesting conundrum.

What could justify not getting a drug to a dying patient in a reasonable period of time, say a few hours or at most a few days?

There is certainly plenty of finger-pointing that could go on.
— The drug company has to produce enough drugs so that it could be made available on a compassionate use basis when the patient is not able to get it in a clinical trial. — Second, a physician at a particular medical facility has to decide that that patient must have this drug and initiate the process of requesting it.
— Third, the hospital’s IRB has to approve use of the drug on a compassionate-use basis. The IRB must be able to convene on an emergency basis and to operate under a protocol that defined acceptable risk for terminally ill cancer patients differently than that for other drugs, such as those treating impotence. In the case of a drug like Viagra, the risk of drug side effects may far outweigh the desirability of getting an erection but rarely would that risk-benefit ratio apply to a cancer drug for dying patients.
— Fourth, the patient must be able to get to that medical facility, overcoming whatever financial obstacles might exist. Here the issue of financial responsibility is a little clearer; it is the patient’s. If the patient is not a citizen of the country in which the medical facility is located, that may involve tens of thousands up-front dollars.
— Fifth, and most important, everyone involved needs to have a sense of urgency similar — just as if the patient had anthrax.

I am sure that some very bright people reading this would be able to present a rationale of why the current situation has to be —- and we invite anyone who wishes to do so to respond through this newsletter. But it would take an awful lot of illumination from the candles we light when one of our members dies to make that acceptable to the families and friends of these patients.

There is a feeling of helplessness as patients and caregivers try to navigate this clinical trial/compassionate use landscape to stay alive. It is easy to believe that this system was just not designed to meet the urgent needs of dying cancer patients.

On the other hand, perhaps we need to shine some lights on the major obstacles to survival that could be overcome with a different set of priorities.

Maybe a time clock showing how long each part of this process takes. On one side of the clock, the names of IRB members and their photographs. On the other side, a list of patients and their photographs. As the clock ticks and deliberations slowly advance, photos of the patients would wink out.

Perhaps there should be other clocks for the other parts of this process, including expanded drug production to meet compassionate use needs, clinician time to draw up protocols and so on.

Tick-tock, tick-tock, tick-tock. Day three: John Doe has died. Tick-tock, tick-tock. Day seven: Jane Doe has died. Tick-tock. Day 17: The IRB convenes.

Dedicated to Ara Jelderian and Mike Matthews. May their heroic struggles not be in vain.

Reprinted from the LRG newsletter January 2005


The governmental agency that controls IRBs is the Office of Human Research Protections in the Department of Health and Human Services at the FDA. However, the FDA has no control over many aspects of IRBs and, before the FDA will approve compassionate use, local IRB approval is required.        

The reality is that each treatment center sets its own protocols in the areas with which we are concerned. There are no requirements as to the frequency of meetings, how quickly they have to consider emergency requests, or what measures they should take to increase their efficiency. They are local fiefdoms run by largely volunteer staffs and the information they must consider is voluminous. Their focus is not on the individual patients who will be affected by their work, but, rather, on the researchers and the entities who are funding the research.

There are two aspects of Institutional Review Boards (IRBs) that concern us:

First, if there are multiple cancer centers that are involved in a clinical trial, each of them has an IRB that must approve the trial. There is a great deal of repetitive effort in this and it all takes time, which delays the trial.

Second, the IRBs are bottlenecks for the approval of a “single user” or “compassionate use” of an investigative new drug (IND). Ultimately, such a use must be approved by the FDA; however, the FDA has requirements that must be met before they will issue such an approval and one of those requirements is IRB approval where the drug will be administered. After the pharmaceutical company and attending physician have approved the use and the patient is prepared to sign any informed consent necessary, some of our members have still waited months for the approval from their local IRB.

IRB culture lacks a sense of urgency and is prioritized toward protecting institutional liability and not patient survival. Further, the process is behind the scenes and rarely sees the light of day. There is no connection made between the way the process works, including its timetable, and the impact upon patient survival. Thus, there is no accountability.