April 23rd, 2012
Selections from Richard Lehman’s Literature Review: Week of April 23rd
CardioExchange is pleased to reprint selections from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
Week of April 23rd
JAMA 18 Apr 2012 Vol 307
Patient-Centered Outcomes: George Orwell predicted a nightmare world where soothing words would mean their opposites, and gave his dystopia the date of 1984. It was about that year that the term patient-centered first appeared in the medical literature, coinciding with the time when the medical-industrial complex went totally out of control in the U.S. and patients were thrown entirely to the mercy of the market. Books and papers about patient-centeredness proliferated in America during the 1990s, but the momentum of medicine there has continued to career in the opposite direction. Now that total chaos and unaffordability loom, the U.S. government has set up the Patient Centered Outcomes Research Institute with a hefty budget to find out how to put things right by finding out what systems of care work best for patients. A laudable aim and a fine-sounding name, certain to arouse suspicion among cynics everywhere; but this particular cynic is amazed and optimistic. To find out why, listen to the visionary speech that Harlan Krumholz gave to the PCORI Patient and Stakeholder group a few weeks ago. This goes way beyond the usual rhetoric of being nice and involving patients, and commits PCORI to a radical agenda of patient empowerment – the only way that health systems the world over can reclaim the true purpose of medicine. This article shows how Harlan’s vision is shared by others in the developing organization.
Uncertainty: But the moment that you attempt to empower patients, you run into problems. Patients as well as doctors like to believe that there must be a single right answer for every problem, when very often there is not. As I’ve said before, Harlan’s surname (meaning crooked wood in German) always reminds me of Kant’s famous dictum, “out of the crooked timber of humanity, no straight thing was ever made.” And it’s no good torturing the evidence by exercises in subgroup analysis and modeling: in most of medicine, there is irreducible uncertainty. Here is a nice short philosophical piece by David Kent and Nilay Shah, headed with the splendid observation of George Box that all models are wrong, but some are useful.
Involving Patients in Research: Three non-clinicians discuss the problems of continuous patient engagement in comparative effectiveness research. Now comparative effectiveness research is actually fiendishly difficult, for reasons I will try to outline very briefly in a moment; and securing patient involvement in research is also difficult, but absolutely essential. In fact it will be a measure of PCORI’s success if it can demonstrate that every aspect of its research is genuinely patient-centered – i.e., that it listens to the patient voice at every stage, and that every output has direct bearing on decision making with patients and society. The ultimate measure of its success, ironically, will be the disappearance of the concept of the patient altogether.
Medicine-Based Evidence: In this hefty themed issue of JAMA, there now follow five examples of comparative effectiveness research (CER), followed by a knotty editorial with the title “Is It Time for Medicine-Based Evidence?” And here is the problem for you and for me, dear Reader: you cannot properly assess a paper on outcomes research or CER without some understanding of the following methods – multiple linear regression or analysis of covariance for continuous (dimensional) outcomes, logistic regression for binary (dichotomous) variable outcomes, proportional hazards analysis or Cox regression when a time interval is relevant to a binary outcome (i.e., survival analysis), and Poisson regression when outcomes are measured as counts. Moving on, you then need to employ these techniques in one or both of two conceptual processes which can help to balance the characteristics of unmatched groups in observational studies: propensity scores and instrumental variables. There are plenty of statistics texts to confuse the unwary, but there is no simple, comprehensible guide to outcomes research for the non-specialist. I know, because I am trying to help write one. And I am hoping somebody else will deal with all this while I write about patient-centeredness. So finally, back to this study. You need not read it: it is simply a good teaching example for those who want to understand the use of propensity scoring in retrospective cohort studies. The study concludes that without needing a randomized controlled trial, we can be pretty certain that adding bevacizumab to carboplatin-paclitaxel chemo for advanced non–small cell lung cancer makes no difference. And that is useful knowledge for decision-making.
NEJM 19 Apr 2012 Vol 366
CABG vs. PCI: Now that we’ve finally escaped from JAMA and all this stuff about CER methodology, let’s look at this first paper in the New England Journal of Medicine. Being in NEJM, funded by the NHLBI, and conducted by a distinguished team of researchers, it must be right, and it concludes that: “In this observational study, we found that, among older patients with multivessel coronary disease that did not require emergency treatment, there was a long-term survival advantage among patients who underwent CABG as compared with patients who underwent PCI.” Proof at last of what we all suspected: new tubes must be better than stents. But hang on, what was the absolute mortality difference between these groups? The median follow-up period was 2.67 years, at which time the survival lines were beginning to diverge in favor of CABG, but not by very much. In the minority of patients followed to 4 years, the difference was statistically significant and stood at an absolute value of 4.4% provided one accepts the methods of the study. And what are these methods? Why, our new friends propensity scores and inverse-probability-weighting adjustment. So we are back to the problems of comparative effectiveness research with a vengeance. The left brain, without the help of complex statistical computation, cannot interrogate these results; while my creaky old right brain tells me that I cannot make use of this information in decision-making with patients, because there are too many variables to rely on such small differences. In fact I think we may need new methods of describing the confidence limits when using these two-stage weighting adjustments with unbalanced groups. So do we need another RCT comparing CABG with PCI using current methods? The editorial discusses this question, but not with any satisfactory conclusion. I think equipoise still best describes the clinical situation.
On- Vs. Off-Pump CABG: And now, like a Common White Butterfly, we must return to the field of cabbage. CABG can, as all of you know, be performed with a cardiopulmonary bypass pump or without. Off-pump CABG is technically more challenging but is supposed to reduce the amount of debris reaching the brain during surgery. This trial (given the unoriginal acronym CORONARY – how much jollier BRASSICA might have been) randomized 4752 patients in 79 centers to have their cabbage done one way or the other. At 30 days, there was no significant difference in gross outcomes, but they acknowledge that “Neurocognitive outcomes and economic data may have an important effect on and substantially influence the ultimate interpretation of the primary findings.”