Unrealistic Optimism

Unrealistic Optimism

George W. Sledge, MD, FASCO

Mar 05, 2011

There is an interesting article by Dr. Pauline Chen in the March 3rd New York Times on the ethics of early phase clinical trials. The article discusses in particular the issue of optimism. Not, as one might fear, the potential for overly optimistic trialists to push patients into trials of novel agents, but rather the “unrealistic optimism” of those who enter such trials with a falsely positive bias regarding their own outcome, despite having received what all would consider appropriate counseling regarding the modest benefits of the average Phase I or II trial. A majority of such patients, according to the recent Hastings Center study quoted in the article, believe that the new agent will control their cancer, despite understanding that the main purpose of a Phase I trial (for instance) is to learn about the dose-limiting toxicity of a new agent. Our own Dr. Neal Meropol, chair of ASCO’s Research Committee, is quoted by the Times commenting on the study.

I cannot say the results surprise me. We are a hopeful species. We cling to life even though we know we all must die. That is the human condition, and neither a detailed informed consent statement nor the care of the clinical researcher in discussing a new agent is likely to change the innate optimism of patients willing to enter a clinical trial.

Is this self-deception? Perhaps. But if so, it is self-deception of a very peculiar kind. Cancer patients live in a world of emerging wonder. They open the newspaper or turn on the television or go online to read about medical and scientific advances every day of their lives. They believe in, if they do not always understand, modern medical science and its prospect for prolonging their lives. They absorb optimism like sponges from their ambient environment. Such optimism may be irrational, but it is certainly not untaught: modern science teaches, and modern society believes in, human perfectability.

The study’s authors point out the ethical dilemmas associated with these biases, and appropriately so. We as a profession (along with our larger society) benefit materially from this optimism, so it is only right for us to maintain a high level of honesty regarding, and modesty about, new therapeutic approaches. The authors find this “unrealistic optimism” ethically problematic, and according to the Times article, “are hoping next to delineate the factors involved in evoking this biased response in patients. By gaining a deeper appreciation of how unrealistic optimism develops, they believe they may be able to help patients and cancer researchers more easily recognize those optimistic biases that impair a patient’s autonomy and compromise the ethics of clinical trials.”

Well, not so fast. To suggest that such optimism is nothing but self-deception on the part of patients with advanced cancer, hence ethically suspect, and something that needs to be fixed in the interest of a higher “patient autonomy,” ignores other realities. The first is that “unrealistic optimism” may not be all that irrational from the standpoint of those facing their own imminent mortality. I think that for many patients we are dealing with a modern form of Pascal’s Wager. The 17th century French philosopher, speaking of belief in God, argued that if God did not exist then you lost nothing by believing in him, but that if he did then you gained the immense benefit of eternal salvation by wagering in favor of his existence. Therefore, even if the odds were low, it was well worth the wager because the payoff was incredibly high.

I have found this cold and calculating religious mathematics (and Pascal was a world-class mathematician) repellant ever since I first read it in my college French class.1 But the medical equivalent of Pascal’s Wager may make some sense in the same coolly rational way. The medical Pascal’s Wager says if you go on a trial and don’t respond then you have lost nothing that wasn’t already lost (i.e., your life was already forfeit), but that if you do not “believe” (lack the “unrealistic optimism” required to go on trial) you lose your (small but real) chance of (therapeutic) salvation. Even if one is statistically unlikely to benefit from a Phase I or II trial, that small but real possibility of hitting the therapeutic jackpot still renders the wager a reasonable one for a patient with advanced disease. There was, after all, a first testicular cancer patient to receive the investigational cisplatin that cured his cancer, and a first CML patient to benefit for a decade from imatinib, and (quite recently) two patients on a Phase I trial with advanced lung cancer who responded to crizotinib. And as early phase trials become more biology-based, with targeted populations, the equations regarding risk and benefit may change (as pointed out by my teacher Dan Von Hoff in his lovely Karnofsky Award lecture). So maybe “unrealistic optimism” is not quite the same thing as “irrational optimism” for some patients.

Pascal’s Wager aside, there is often more to a patient’s willingness to go on trial than “unrealistic optimism.” I have heard the same words literally dozens of times from my patients: “Even if this won’t help me, maybe it will help someone else.”  There are deep wells of altruism that we dip into when we perform clinical trials. It is important that we not pollute those wells by taking unfair advantage of vulnerable patients; it is equally important that we not discount them.

And it is yet more than altruism. There is another word we use to describe someone who willingly and confidently places his or her life in peril in the face of seemingly impossible odds. The word describes something messy, irrational, unscientific and hard to quantitate. It doesn’t need fixing, it wants celebrating. The word is “courage.”

1Nor even particularly smart. Certainly an omniscient and omnipotent creator must be able to recognize when someone is trying to game the system, and--not unlike the ASCO Program Committee—knows enough to reject the abstract. Pascal also was famous for saying, on contemplating the universe, that “"Le silence eternel des ces espaces infinis m'effraie”: the eternal silence of these infinite spaces frightens me. Blaise Pascal was not a guy who faced his own non-existence with any equanimity.


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Sue Bock, RN

Mar, 17 2011 1:11 PM

When one receives a cancer diagnosis there is an instant connection to a community. This bond sets the stage for communal desire to help themselves and help others. Unrealistic or irrational optimism may be what the medical community wants to label the feelings these participants have, but as a breast cancer victor I know that these clinical trials represent hope. Hope is an eternal human condition that wants to believe that good will come out of a situation. This hope, this faith, is sometimes what gets a patient through a miraculous journey. There is no reason to remove that from any cancer diagnosis equation. As an ICU nurse, I have seen many a miracle when there were no other options. A cancer patient will utilize all aspects of treatment including faith, hope, community, alternative treatment, just to find the best way to go through the process. I ask, "why not?"

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