Friday, March 10, 2006

Complexity, Conflicts of Interest, and Cancer Doctors' Decisions About Chemotherapy

The New York Times recently reported on research suggesting the susceptibility of physicians to financial incentives. The research, and how it was reported, illustrate the complexity of untangling issues of conflict of interest affecting physicians and other health care decision makers.

To summarize, the Times reported on a study just published in Health Affairs that found "providers who were more generously reimbursed prescribed more costly chemotherapy regimens to metastatic breast, colorectal, and lung cancer patients." The Times noted that "unlike other physicians, cancer doctors can profit from the sale of chemotherapy drugs in a practice known as the chemotherapy concession." So, "while critics say this creates a potential conflict of interst among oncologists advising patients on treatment, the doctors have said that the profit is needed to pay the high cost of running their practices." The Times then quoted opposition to the notion that physicians' decisions were ruled by conflict of interest from an "executive" [actually, Interim Executive Vice President and CEO] of the American Society of Clinical Oncology, Dr Joseph S Bailes, who said words to the effect that "cancer doctor select treatments only on the basic of clinical evidence." The Times then interviewed the study's senior author, Professor Joseph P Newhouse of Harvard, who argued that "there is little evidence that one chemotherapy drug works better than another, [so] 'the physicians have more control over the agents chosen.'" Bailes countered that "there was clear clinical evidence about which drugs should be used even in advanced stages of the disease and that doctors recommend the most appropriate treatments." But Dr Craig C Earle, another study author, had the last word, arguing that "doctors, despite their insistence that their treatment decisions are based solely on what is best for the patient, are affected by payment policies and other financial influences, including gifts from drug companies...."

So what really is the message, that physicians make appropriate decisions based on the evidence, or that they are influenced by financial incentives, including gifts from drug companies? The Times reported the research results in the context of a tit-for-tat among the articles' authors and the ASCO CEO. By giving the authors more air time and the last word, the Times seemed to slightly favor their point of view.

To try to get a clearer fix on this, I did a quick review of the study itself. [Jacobson M et al. Does reimbursement influence chemotherapy treatment for cancer patients? Health Aff 2006; 25: 437-443. The link is here.]

This was a retrospective cohort study, apparently using physicians as units of analysis. Data was obtained from the Surveillance, Epidemiology and End Results (SEER) cancer registry, and Medicare administrative data. The costs of chemotherapy drugs physicians prescribed for patients with lung, breast, or gastrointestinal metastatic cancer were compared across physicians to the average chemotherapy reimbursements per drug received by the physicians, controlling for some characteristics of the patients seen by them in a fiendishly complex statistical analysis. Reimbursement was not correlated with the rate physicians employed chemotherapy, but was correlated with the Medicare spending per physician on chemotherapy.

So this was not an easy study for rapid critical review. My main concern is that the observational study design was susceptible to study biases. In particular, physicians who received higher reimbursement rates may also have had patient populations who differed, especially in terms of disease severity or patient preferences, from those who received lower rates. These differences, rather than differences in reimbursment rates, could have been the main reason they selected different treatments. The complexity of the analyses makes it harder to assess the study, especially given that their results were presented only in brief summary form.

Do cancer physicians make decisions about specific chemotherapy drugs for patients with metastatic disease based on the evidence and patient preferences, or on financial incentives? I am not sure that the study gives a clear answer (and was not designed to give an either or answer).

For what it's worth, my gut feeling is that most physicians try to make decisions based on evidence, on patients' characteristics and their preferences, but that it is hard not to be influenced by other factors, including financial incentives.

I should also note that the only financial incentives the study analyzed were Medicare reimbursement rates. Conflicts of interest, such as gifts by pharmaceutical firms to physicians, may affect their decisions, but this study was not designed to assess such conflicts. Hence Dr Earle's last comment may reflect his beliefs, and may be true, but does not follow from this single study's results.

Furthermore, just to further confuse the issues, it appears the study and its reporting may also have been affected by different kinds of conflicts of interest. The Health Affairs article does not mention any relevant conflicts of interests affecting the authors of the study. But Professor Newhouse, the senior author, has disclosed in other articles (for example, here) that he has a financial interest in Aetna, Inc, the large, for-profit managed care company (which, in turn, is likely interested in reducing physicians' utilization of expensive drugs). In fact, he is a member of Aetna's Board of Directors. (See Newhouse's most detailed biography on the Harvard web-site, confirmed on the Aetna web-site here.) Thus, he has a particularly strong conflict, since he has a fiduciary responsibility to protect the financial interests of Aetna Inc and its share-holders.

So maybe this is all another argument for what I have said before about conflicts of interest: I suggest developing a broad set of principles about conflicts of interest, and generally about business ethics in health care, focused on all transactions with outside organizations with their own vested interests or agendas. These principles should apply to all who make decisions in health care, physicians, other health care professionals, and leaders of health care organizations. The details of the implementation of these principles could vary, so as to apply to the setting and role of each individual.

8 comments:

David E. Williams said...

This certainly is a complex issue and I don't think there's any easy way around it. One lesson from the financial services industry is that even when conflicts of interest are disclosed (e.g., in stock analyst reports) the reader tends to ignore the conflicts.

I'm a proponent of making physicians more aware of the influences that they are subject to. For example, there should be better medical school courses on the economics of the pharmaceutical, device and managed care industries so doctors can understand what they are a part of.

matthew said...

Roy. I really appreciate your desire to see the full truth behind all these studies. Myself, I'm a little more cynical. When CMS wanted to change the way they part for Part B chemo drugs ASCO went bananas, my limited sources told me that the average oncologist was liable to lose up to 100K a year. GAO did a study, basically turning the tables on ASCO, saying that if they weren't gilding the lilly before, then they wouldnt lose much money. Pretty funny I thought, but you can tell how much this matters by looking at the oncologists reactions -- and their reactions are clear. They make their margin by doing more and more expensive chemo, while those salried docs in university settings do things very differently (as Greg P points out in my blog).

Still I'm delighted that you spend o much time looking behind the studies and the news (as in the recent Newhouse and Shalala examples)

Steve Beller, PhD said...

This just confirms my contention that a knowledge void is a big part of our healthcare crisis. If we all knew the most cost-effective interventions (and preventions) for each patient, and had a healthcare system that enabled them to delivered effectively and efficiently, then we wouldn’t have these kinds of problems and we’d be well on our way to solving the healthcare crisis!

So, I ask, is there clear clinical evidence about which drugs oncologists should prescribe for each particular patient? Is there really so “little evidence that one chemotherapy drug works better than another” that we can’t agree on personalized plans of care? And if so, what has to happen in order to gain this requisite knowledge and use it wisely for the benefit of patients and society?

Greg Pawelski said...

As the number of possible treatment options supported by completed randomized clinical trials increases, the scientific literature becomes increasingly vague for guiding physicians. Almost any combination therapy is acceptable in the treatment of cancer these days.

Physicians are confronted on nearly a daily basis by decisions that have not been addressed by randomized clinical trial evaluation. Their decisions are made according to experience, new basic science insights, bias or personal preference, philosophical beliefs, etc..

There is a mind-set of cancer culture that pushes tens of thousands of physicians and scientists toward the goal of finding the tiniest improvements in treatment rather than genuine breakthroughs, that rewards academic achievement and publication over all else. Tumor shrinkage should not be the criteria for approving cancer drugs.

Metastasis is an organism-wide phenomenon that may involve dozens of processes. It's hard to do replicable experiements when there are so many variables. So, instead, researchers opt for more straightforward experiments that generate plenty of reproducible results (like tumor shrinkage). This gives the illusion that researchers have done something meaningful.

A patient responds to therapy when their tumor shrinks, but apparently this has nothing to do with survival. A tumor responds, that is, shrinks a little, then quickly grows and spreads. The cancer comes back with a vengeance and the cancer patient is given a death sentence by his/her oncologist who will wash his hands of it.

The needed change in the "war on cancer" will not be on the types of drugs being developed, but on the understanding of the drugs we have. The system is overloaded with drugs and underloaded with the wisdom and expertise for using them.

gpawelski said...

As the number of possible treatment options supported by completed randomized clinical trials increases, the scientific literature becomes increasingly vague for guiding physicians. Almost any combination therapy is acceptable in the treatment of cancer these days.

Physicians are confronted on nearly a daily basis by decisions that have not been addressed by randomized clinical trial evaluation. Their decisions are made according to experience, new basic science insights, bias or personal preference, philosophical beliefs, etc..

There is a mind-set of cancer culture that pushes tens of thousands of physicians and scientists toward the goal of finding the tiniest improvements in treatment rather than genuine breakthroughs, that rewards academic achievement and publication over all else. Tumor shrinkage should not be the criteria for approving cancer drugs.

Metastasis is an organism-wide phenomenon that may involve dozens of processes. It's hard to do replicable experiements when there are so many variables. So, instead, researchers opt for more straightforward experiments that generate plenty of reproducible results (like tumor shrinkage). This gives the illusion that researchers have done something meaningful.

A patient responds to therapy when their tumor shrinks, but apparently this has nothing to do with survival. A tumor responds, that is, shrinks a little, then quickly grows and spreads. The cancer comes back with a vengeance and the cancer patient is given a death sentence by his/her oncologist who will wash his hands of it.

The needed change in the "war on cancer" will not be on the types of drugs being developed, but on the understanding of the drugs we have. The system is overloaded with drugs and underloaded with the wisdom and expertise for using them.

Steve Beller, PhD said...

Superb post by gpawelski! We’re drowning in data and information about diagnostics and treatment options, but clinicians often don’t have useful knowledge they can use in everyday practice to help determine what is are the best interventions for particular patients. And when researchers can’t even agree on how to define good outcomes, whew, do we have a problem!

Does anyone have any comments on the idea of establishing professional networks in the public interest that enable clinicians to report observations and hypotheses and give ideas to researchers who design clinical trials that generate evidence-based knowledge truly useful to clinicians?

Steve

shannon brownlee said...

Thanks for the analysis, Roy. Despite its complex statistics and conflicts of interest, I suspect there is at least a grain of truth to the Newhouse study. Oncologists tell me that they run their practices in part on profit from chemo (and that includes oncologists with academic positions who often also have private practices). Chemo profits pay for nurses, who are the lifeblood of oncology practices, because patients need a lot of handholding as well as hands-on care.

The problem with this payment system is obvious. Despite the countless studies in oncology, which must be the most clinical-trial intensive specialty outside of cardiology, the differences between different chemo-cocktails don't make a hell of a lot of difference in a metastatic patient's survival.

One question I have is whether the drug industry cuts deals with oncologists, the way it does in some other specialties. It offers them below-average prices in exchange for volume. So one physician may use one drug more than another because he or she has a contract with the manufacturer.

It's worth noting the rise in the use of chemo on patients with localized tumors, as well asthose with metastatic disease. Look at the stats for breast cancer. About 60 percent of breast cancers--about 120,000 cases per year--are localized. Of those, 70 percent, or about 84,000 women, would be cured by surgery alone. (An unknown number would have been fine--i.e., their tumors would have disappeared on their own or never become symptomatic--even without surgery.) Yet nearly everybody gets radiation and another 62 percent get chemo or hormone therapy, because there are few prognostic indicators to tell oncologists who is going to benefit from the radiation and drugs. The result is a small reduction in recurrence. There is some thought that all of the improvement is due to tamoxifen, not the adjuvant chemo.
http://www.newamerica.net/index.cfm?pg=article&DocID=813

As a patient, I think I would feel a lot better if I knew my physician did not have a financial interest in giving me drugs that might or might not improve my chances of not dying prematurely, but will almost certainly give me unpleasant side-effects.

gdpawel said...

The study adds to the 'smoking gun' survey by Dr. Neil Love, entitled "Patterns of Care." One of the results of this survey shows that for first line chemotherapy of metastatic breast cancer, 84-88% of the academic center-based oncologists (who do not derive personal profit from infusion chemotherapy) prescribed an oral dose drug (capecitabine), while only 13% prescribed infusion drugs, and none of them prescribed the expensive, highly remunerative drug docetaxel.

In contrast, among the community-based oncologists (who do derive personal profit from infusion chemotherapy), only 18% prescribed the oral dose drug (capecitabine), while 75% prescribed infusion drugs, and 29% prescribed the expensive, highly remunerative drug docetaxel. (Patterns of Care: 2005,Vol 2,Issue 1).

While the Michigan/Harvard study showed results before the new Medicare reform, the Patterns of Care study showed results that the Medicare reforms are still not working. It is still an impossible conflict of interest.

And the existence of this profit motive in drug selection has been one of the major factors working against the individualization of cancer chemotherapy based on testing the cancer biology.

The two scientific studies are giving us a dose of reality. Once a decision to give chemotherapy is taken, oncologists receiving more-generous Medicare reimbursements used more-costly treatment regimens.

It's not that all oncologists are bad people. It's just that it is still an impossible conflict of interest (i.e. it's the SYSTEM which is rotten). Some oncologists prescribe chemotherapy drugs with equal efficacies and toxicities. I would imagine that some are influenced by the whole state of affairs, possibly without even entirely admitting it. There are so many ways for humans to rationalize their behavior. The solution is not to put the doctors in jail, it's to change the system.

http://patternsofcare.com/2005/1/editor.htm