Making decisions … and making them work

This year is characterized by making a leadership decisionof sufficient importance to attract a huge amount of our attention and cashflow, albeit only about 0.015 percent of our $15-trillion gross nationalproduct. How do we make decisions? Do we analyze Democrats and Republicans withrespect to their overall "comparative effectiveness," or is it their"comparative ineffectiveness" that influences our thinking? It's generallysettled that many joined one tribe or the other and stick with it out of familytradition and to avoid being labeled disloyal or a flip-flopper. A relative fewvoters make the difference in the outcome, and both tribes pander to theiremotional hot buttons, rather than the integrated whole.

Does past performance predict the future? I'm reminded of that phrase investment fundsuse: "Past performance is not indicative of future results." This suggests bothhope and fear. Why not use the same honest phrase for climate change ormammography, the PSA test or the product insert for a drug? It pretty muchprovides cover for decisions on how to vote, buy wine or to cheer for theChicago Cubs.

Four decades ago, Prof. Ron Howard of Stanford University,an expert on decision analysis, introduced the term micromort, a unit of risk, anda one-in-a-million chance of death. The concept has been broadly applied acrossmany human activities, including those that put us in motion with exposure toNewton's laws by bungee jumping, flying, driving, skiing and the like. Thereare less immediate risks, such as exposure to sunlight, nitrosamines, cosmicrays, osteoporosis drugs or anesthesia. A confounder of such a formality is thehuman tendency to be influenced by short-term observations, such as a recentcruise ship mishap off Italy.

The egregious behavior of Enron and Tyco executives, BernardMadoff or the "London Whale" at J.P. Morgan also come to mind as rare events. Hopefulinvestors gambled in collusion with professionals, and they lost. Cruise linesreport ca. 0.1 micromorts encountered per ticket purchased. For commercial airtravel globally, the numbers in recent years have averaged <0.003 micromortsper million passenger kilometers traveled, <3 nanomorts/km. Considering theUnited States alone, we've fortunately had no such fatalities in five of theyears since 2001.

But what is the risk of dying of any cause in any givenyear? Today, in the United States, that number is 8 millimorts/year across theages, from 1 mm/y in the college years to 50 mm/y from 1975 to 1984. About 5mm/y on average can be attributed to a combination of malignancies andcardiovascular disease.

I've long contended that the risk of disease is given lessattention than the risk of treatment, even though disease prevention is an availableoption often not taken. I stick with my theme that medical interventions shouldbe relatively safe and relatively effective and relatively economic compared toallowing disease to progress untreated.

Micromorts are thought-provoking and can also be stress-inducingat my age. With respect to drugs, there are a variety of confusing terms thatare not consistently applied, but are important to differentiate. These includemedication errors, adverse drug events, adverse drug reactions (ADRs), sideeffects and hazard ratios.

Errors are mistakes related to human failings in writing orreading prescriptions, dispensing, patient adherence to the dosing regimen ormisdetermining circulating concentration. An event is harm done by a drugitself, whatever the cause. A reaction is an unintended drug response caused bynormal use, such as an allergy, headache or QT interval prolongation in theECG. This term is frequently used synonymously with side effect. A hazard ratiodescribes a relationship between one drug and another with respect to aspecific unintended outcome.

ADRs are typically listed in direct-to-consumer advertisingwith no attached probabilities, for which we propose the impractical microADRsor milliADRs. A recent New EnglandJournal of Medicine paper (May 17, pages 1,881-1,890) is titled "Azithromycinand the Risk of Cardiovascular Death." The authors examined responses to atypical five-day course of therapy and compared with the use of two alternateantibiotics or none. During the five-day period examined, there were 29.8micromorts for no antibiotic, 31.5 for amoxicillin and 85.2 for azithromycin.The latter showed a hazard ratio of 2.88 for azithromycin versus no antibiotic.

The paper is well done, but context is very important. Acolleague saw a summary and asked, "Is azithromycin really three times moredangerous than other antibiotics?" All subjects were Medicaid patients; 77.5percent were women with a mean age of 48.6, and many were prescribedmedications for hypertension. The authors wisely described the risk as slightand small. Yet my colleague was thinking triple the risk!

Too often, we read of the relative risk of drug A versus drugB without benefit of the absolute risk of either in relationship to theabsolute risk of the condition treated. The same ambiguities apply tomammograms and PSA tests. We see the statistics, yet we still can't decide. Asensible decision for a population may have a bad outcome for an individual.This is what scares people about the concept of comparative effectiveness.

Returning to politics, I hear that one tribe is perpetratinga "war on women" and the other "favors abortion." One tribe wants to "eliminateall regulations on business," while the other "wants gas to be $10 a gallon."None of these are factual. When will we learn that campaigning and governingcorrelate very poorly? While it's true that past performance may not beindicative of future results, if you flip a coin 99 times and it comes up headseach time, I'm voting that something is funny, and the next flip will also comeup heads.

An evidence-based decision suggests the crowd in eithertribe in Washington, D.C. is prone to adverse reactions and high hazard ratioscompared to some cohorts we've seen in the past. Let's take them off the marketand try again until we get something that works.

Peter T. Kissinger isprofessor of chemistry at Purdue University, chairman emeritus of BASi and adirector of Chembio Diagnostics, Phlebotics and Prosolia.