Should I Enter a Clinical Trial–Part Three

An Example of What Happened

We would like to provide a concrete example about the consequences of participating in a clinical trial. It is based on Amanda Bennett’s The Cost of Hope. She is a fine journalist and currently Executive Editor of Projects and Investigations at Bloomberg News. The book documents her husband, Terence Foley’s, seven year bout with kidney cancer. Initially, Foley was diagnosed with an atypical and aggressive form — collecting duct kidney cancer. It was spotted in December 2000 during the operation to remove his intestines to treat his ulcerative colitis. There were only 50 known cases of it worldwide at the time. This alone makes questionable whether his participation in the clinical trial contributes to our understanding of the potential benefits for future patients. In January 2001 when it was diagnosed, the prognosis was that he had a few months to live. [Bennett, p. 66] He died of it seven years later in December 2007.

The clinical trial

In August 2002 when the cancer had spread to his lungs, a new doctor put Foley on “watchful waiting.” His condition was monitored with periodic scans and no additional treatments. After various treatments, in December 2005, 3 years and 5 statsmonths later, the cancer in his lungs flared up again. At the doctor’s suggestion Foley agreed to enter a clinical trial. It began at the end of February 2006. It involved two drugs — Avastin and Nexavar. Avastin was administered by infusion once every two weeks, Nexavar with a daily pill. Things didn’t go too well. After three months, because of severe side effects, the dosage of Avastin was reduced. Three months later he was taken off Nexavar. He continued with the Avastin and the tumors got smaller. In spite of that, after being on the trial for fifteen months, he dropped out of it all together because the side effects — fatigue, stomach ailments and rashes — were so severe. [Bennett, pp. 156, 163-4 and 186]

While most of the expenses were covered while he was on the trial, Foley was charged $45,356 for the fourteen CAT scans that monitored the progress of the cancer. The insurance companies paid $32,584. Foley didn’t pay anything out-of-pocket for the drugs or their administration. [Bennett, p. 180] Nonetheless, Foley and the family incurred other real and financial costs because of his participation in the trial. They included the extra debility, pain and suffering, the time, effort and income lost because of his participation, and whatever added expenses the family incurred. They were all the result of Foley’s enrolling in the clinical trial. Importantly, they gave up whatever else they could have done with that time and money.

Remember that Foley had a rare form of kidney cancer. Moreover, since previously his colon had been removed, one could easily say that he was not the typical patient. Whatever his response to the treatment turned out to be, the outcomes are of questionable value for future patients. Nonetheless, the doctors recommended that Foley enter the trial and he did. In technical terms, Foley’s participation leads one to question the applicability of the results.  For the results of any clinical trial to be a good predictor of outcomes, subsequent patients must have the same characteristics as those in the trial. If not, the doctors who prescribe the drug and their patient are flying by the seat of their pants. Outcomes predicted by the trial are simply not relevant and the decision to take the drug is not supported either by evidence-based medicine or even by experience-based medicine.

Compared to the alternative

In order to understand the consequences of Foley’s entering the clinical trial, it is useful to compare it to what his life would have been like had elected not to do that.  Fortunately, in the 3 years and 4 months prior to entering and in the 5 months after, he was on the “watchful waiting” protocol. The alternative to participating in the trial would have been that Foley remained on “watchful waiting” during the fifteen month period. Had he done so, here is a suggestion of what the likely benefits and costs of that decision would have been. Clearly, it is speculative, nonetheless, in his case we have a good idea, medically, of what his life would have been like.

The benefits of not entering the clinical trial would be that Foley and the family would not have incurred the real and financial costs described above. Even though we don’t have all the numbers, here are those we have. By being on watchful waiting during the fifteen months there would have probably been two scans. Instead of the $45,356 charged for fourteen of them, the charges would have been $6,464 with the insurance companies paying $5,172 or less. [Bennett, pp. 156-7] Furthermore, Foley and the family would have avoided the real and financial costs associated with the debility, pain, suffering and anxiety from the administration of the clinical trial drugs, Avastin and Nexavar. While it is difficult to assign a value to those costs, there is no question that they are nonetheless indisputable and present. That they were significant enough to cause Foley to withdraw from the trial is clear proof that those costs exceeded the benefits. They would not have occurred had Foley been on watchful waiting.

There are some possible benefits resulting from Foley’s participation in the trial. Remember his condition was quite unique. To the extent that his experience is relevant and that it can be associated with the administration of the drugs, Avastin may reduce the size of the tumors but not necessarily extend the length of life.  Another is that Foley’s participation provides a better understanding of the nature and severity of the side effects that result from taking those drugs in combination and in taking Avastin alone. Had he not entered the trial we might not have that information.

If you have any question about the stakeholder’s interest this is what happened to Foley after he had to withdraw from the trial. The doctor wanted to put him back on Avastin, but since it had not yet been approved that required special permission, which the FDA granted. Since he was no longer on the trial, the company, Genentech/Roche, charged him $27,360 per dose, or a total of $109,440, for the four doses he took before he died. Of that the insurance company paid $26,644. Foley did not have to pay anything out-of-pocket. [Bennett, 186-7] The company insisted on charging for the medications even though they were not yet approved and in spite of the fact that Foley had voluntarily agreed to participate in their trial. He had made the sacrifice and only withdrew because of the side effects.

In our fourth and final post on clinical trials we will provide suggestions about what you and your patient advocate should consider before saying yes to entering one.

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