5th Annual International Bioethics Conference, Harvard University, April 22-23, 2010

If you or one of your loved ones were seriously sick with cancer, with a prognosis of only a few weeks left to live, would you want to spend them receiving aggressive chemotherapy or spending those at home or in a hospice, receiving palliative care?

Probably, if you knew that the probability of therapeutic benefit given by a 3^rd or 4^th line chemotherapy would be minimal (the much heralded targeted ‘clever’ molecules produce 6 to 10 weeks prolongation of survival in kidney cancer with accompanying toxic effects assured), you might opt out.

The reality, though, is different, as about one third of cancer patients still receive anti-cancer therapy as some form of chemotherapy within two weeks of death. At least, this is the US situation, as was described by Lowell Schnipper (Theodore W and Evelyn G Berenson Professor at Harvard Medical School, and Chief of Hematology/Oncology, Beth Israel Deaconness Medical Center, Boston), who opened the first session on 'Decisions about Expensive Cancer Drugs: The US Public and Private' of the 'Priorities in Health: Can we make better decisions?' (V Annual International Bioethics Conference organized by the Harvard University Program in Ethics and Health, April 22-23, 2010).

On the one hand, Lowell recognized that often requests for active treatment come from patients, who want to be treated instead of receiving palliative care, because they want to feel they have done whatever it was possible to fight the cancer, and do not want to admit to be terminally ill. On the other hand, Lowell also pointed out that in most cases patients are not properly informed by their doctors about the actual benefits and toxicities of the active therapies, and only a minority frankly discuss with their doctors the possibility of imminent death.

Matsuyama and coauthors recently argued that more prospective information about how patients make their choices, and what they would consider a good choice, would better inform decision making. They also argued that both decision aids and honest, unbiased sources to inform patients of their prognosis, choices, consequences, and typical outcomes are needed to assist patients in making decisions concerning management options at the end of life (Matsuyama et al, JCO 2006).

This year, Smith and Hillner tackled this issue from a different perspective, namely by comparing the (high) cost of active therapy vs the (not so high) cost of palliative care and psychological support. In their paper, Smith and Hillner show that current incentives for cancer treatment in the US are often misaligned to reward the most aggressive and expensive actions, as these lead to the highest return to the clinical oncology practice (Smith et al, Oncologist 2010). As Smith and Hillner bluntly put it: “This avoidant behaviour has its consequences. It is easier, and more financially rewarding [for the medical oncologist], to continue giving chemotherapy until the end is beyond doubt”. Some consequences of this 'avoidant behaviour' for the US healthcare system include cancer treatment costs being twice as high compared to those of any other nation with either minimal or no difference in survival, and late referrals (if at all) to hospices. The median length of stay in a hospice has declined from 29 days in 1995 to 26 days in 2005, with one-third enrolling in the last week of life and 10% on the last day of life (Harrington et al, JAMA 2008).

So, what could be done in practice to bend the increasingly steep cancer curve and reverse this trend, which is useless -if not frankly harmful- for the patients, while being also economically unsustainable? Lowell described the efforts recently taken by ASCO (American Society for Clinical Oncology) in this direction.

Among these, the 'Quality of Oncology Practice Initiative' (QOPI® ), a self analysis within the oncology practice prepared by ASCO. The 'QOPI' (http://qopi.asco.org/ ) aims at creating a culture of self-examination for medical oncologists. The process includes measurement and feedback tools for haematology-oncology practices, which will be registered to participate in large data collections with the goal of improving quality of cancer care.

Another initiative led by ASCO and aimed at better resource allocation in cancer care is represented the 'Cost of Care Task Force', which was chaired by Lowell and that resulted in the Cost of Cancer Care Guidance Statement which was published in July of last year (Meropol et al, JCO, 2009).  ASCO’s Cost of Care Task Force developed this statement to raise awareness in the oncology community about the many factors at work that are driving the increasing costs of cancer care. As emphasized by Lowell at the conference; “we have to acknowledge that we drive the costs of care by what we do, and don't do”. The utilization of effective but expensive drugs in cancer care plans contributes to the increasing costs of cancer care and, in contrast to other markets in which the consumer is the sole judge of value, the demand for medical interventions is, in part, driven by the prescribers (Meropol et al, JCO, 2009).

To spell out the terms clearly, Lowell identified three main factors that are responsible for the increasing costs of cancer care, namely:

• for various reasons, too much chemo is given to patients at the end of life (Harrington & Smith, JAMA 2008);
  
  
• out of financial self-interest, doctors choose to prescribe the type of chemo that makes the most profit for the practice, e.g. docetaxel instead of generic paclitaxel (Smith & Hillner, The Oncologist 2010).
  
  
• without chemo and supportive drug profits, oncology is a very poorly paid specialty with a very tough job. As honestly written by Smith & Hillne; “for many of us, haematology/oncology is a 24/7/365 responsibility, unlike some other medical specialty practices. We have direct responsibility for outcome with the disease (at least a little bit), routinely deal with fractured dreams and extreme suffering, and are at risk of burnout. This is not something most oncologists would want to do for a low salary”. (Smith & Hillner, The Oncologist 2010)

Lowell hopes that the ASCO Statement, together with the QOPI and possibly other similar tools, will both assist oncologists in understanding issues related to cost of care for patients, and provide a rationale to integrate discussions of cost into treatment decision making as a component of high quality care. According to Lowell, “it is no longer sufficient to simply identify that a treatment’s benefits outweigh adverse effects”. Rather, oncologists must be able to discuss how much benefit might be expected from a particular therapeutic option.  Discussions of value may be informed by data provided by comparative effectiveness and cost-effectiveness analyses. (Meropol et al, JCO 2009).

ASCO recommends that such analyses should be also included within the design of clinical trials, together with data on safety, efficacy and toxicity.  For example, appropriately designed clinical trials should be conducted to provide physicians with increased resources to help their patients assess the value they assign to particular treatment options. Moreover, research to identify strategies for determining 'value' in cancer care is required.

On a related point which was not explored by Lowell in his talk, and that we only mention here;  the option of being enrolled in a clinical trial should be considered, together with recovery in a hospice, for terminal patients.

While it is the case, of course, that for most clinical trials the probability of therapeutic treatment will be minimal and comparable to 3^rd or 4^th line chemotherapy, other issues would need to be considered when assessing the 'value' of participating in a research study. Indeed, the participation in a clinical trial may add an extra 'value' for the patient, who may benefit psychologically from knowing that his or her participation is contributing to the advancement of medical knowledge, and that they are in some sense reciprocating patients who were enrolled in clinical research studies in the past (the readers interested in the ethical debate concerning participation to research could read Schaefer et al, JAMA 2009 and references therein).

References

Matsuyama R, Reddy S, and Smith TJ. Why Do Patients Choose Chemotherapy Near the End of Life? A Review of the Perspective of Those Facing Death From Cancer, JCO 2006: 3490–3496.

Smith TJ, Hillner BE. Concrete Options and Ideas for Increasing Value in Oncology Care: The View from One Trench, Oncologist 2010; 15 Suppl 1:65-72.

Harrington SE, Smith TJ. The role of chemotherapy at the end of life: “when is enough, enough?”JAMA 2008;299(22):2667-78.

Meropol NJ, Schrag D, Smith TJ, et al. ASCO guidance statement: the cost of cancer care. JCO 2009;27(23):3868-74.

Schaefer GO, Emanuel EJ, Wertheimer A. The obligation to participate in biomedical research. JAMA 2009;302(1):67-72