Wednesday, July 25, 2012

Medicine as the trolley problem

Are you familiar with the trolley problem? It is an ethics dilemma first formulated by the great Philippa Foot as a part of a series of such dilemmas. Her formulation goes roughly like this. Imagine there is a tram hurtling down a track. If it keeps going straight, it will hit and kill 5 people who are working on that track. The conductor is able to throw a switch and divert the train to another part of the track, where 1 single worker will be killed by the trolley. The question is what should the conductor do? Most people when asked respond that yes, he should throw the switch and sacrifice 1 life to save 5. After all, the net benefit is n=4.

There are literally thousands of alternative formulations of this problem, but one of them from the philosopher Judith Jarvis Thomson merits special consideration. The problem starts out similarly, with 5 lives on a track in potential peril. The vantage point and the solution are quite different, though. Now there is a bridge over the rail track, and a very large man is looking at the tracks from the bridge. One way to stop the train is to throw a heavy object in its path, like this large man, for example. You are on the bridge standing behind the man. Would you be justified in pushing him off the bridge in front of the tram to meet his death in order to spare the 5 workers down the tracks? Most people when faced with this formulation say an emphatic "no." This is somehow puzzling, since the net benefit is the same, n=4, as in the original Foot formulation.

Philosophy professors have puzzled over this difference for decades, and there are several potential explanations for why we respond differently to the two scenarios. One explanation has to do with the proximity of the operator (conductor in the first case and the person doing the pushing in the second) to the sacrificial lamb -- in the first case one is enough removed from the action of killing by merely redirecting the tram, whereas in the second the action is, well, more active, and the operator is actually pushing an innocent person to his death.

Though in some ways the scenarios seem to bear no practical distinction from one another, we see the morals and ethics of each differently. This difference in the view point is instructive to the field of medicine, where it has implications to how policy relates to the individual patient encounter. Here is what I mean.

Suppose you are a policy maker, and you recommend that every woman at age 40 start to receive an annual screening mammogram to reduce deaths from breast cancer. At the population level, if we screen 1,000 women for about 30 years, we will save approximately 8 of them from a breast cancer death. (Yes, it's 8, not 80, and not 800). At the same time, among these 1,000 women, there will be over 2,000 false alarms, and over 150 of these will result in an unnecessary biopsy. Some of these biopsies will incur further complications, though currently we  do not seem to have the data to quantify this risk. But what if even one of these biopsies were to lead to death of or another dire lasting complication in a woman who turned out not to have cancer? And by the way the accounting is not all that different when applying the new USPSTF mammography screening recommendations. Well, then we have the trolley problem, don't we? We are potentially sacrificing 1 individual to save 8. And who does the sacrificing is where the variations of the trolley problem come in.

Payers levy financial penalties on primary care physicians when they fail to comply with screening recommendations in their patient panels. The payer certainly sees this issue as the original formulation of the problem: Why not throw this financial switch to achieve net life savings? But for a clinician who deals with the individual patient this may be akin to pushing her over the bridge toward a potentially fatal event. Because we don't have a crystal ball, we cannot say which woman will die or incur a terrible complication. But the same population data that tell us about benefits must also give us pause when reflecting on the risks. Add the ubiquitous uncertainty (and lack of data) into this equation, and the implications are even more shocking. So, while making policy recommendations based on population data is sensible, policing uniform application of these recommendations to individual patients is fraught: of course, clinicians and patients need to be cautious about making individual decisions even when in population data benefits outweigh risks.

On the surface risk-benefit equations for many interventions may appear favorable, leading to blanket policy recommendations to employ them on everyone who qualifies. In the office, the clinician, caught in a tug of war between mountains of new literature and the ever-shrinking appointment times, is hard-pressed to take the time to consider these recommendations in the context of the individual patient. And furthermore, financial incentives from payers act as a short-hand justification, a "nudge," for doing as recommended rather than for giving it thought. So, who must look out for the patient's interest? The patient, that's who. Who understands the patient's attitude toward the risks and the benefits? The patient, that's who. Who now has to be responsible for making the ultimate informed decision about which track to stand on? The patient, that's who.

For me the trolley problem gives clarity to the reservations that I walk around with every day. I have done a lot of soul searching about why it is that, even if the benefits seem to outweigh the risks, I am still more often than not skeptical about whether a particular intervention is right for me. And since every intervention in medicine has a real risk, though mostly quite low, of going terribly awry, my skepticism is justified. This is my approach to evaluating these risks and benefits, based on my values and my understanding of the data as it is today.

What's the answer to this ethical conundrum in medicine? I cannot see that policy makers will stop throwing the switch in the near future, and so as a society we will be forced to accept the tram's collateral damage. And while this may make sense in an area such as vaccination, where thousands of lives can be saved by sacrificing a very few by throwing the switch, in most everyday less clear-cut medical decisions the answer is less clear-cut. Will doctors rebel against being forced to throw some patients on the tracks in order to save some marginally larger number of others? I don't think that they have the time or the energy or the incentive to do this, since the framing of the switch-throwing is through the rhetoric of "evidence." Right or wrong, doctors are shackled by the stigma of ignorance that comes with not following evidence-based guidelines, and this may act to perpetuate blind compliance. This leaves the patients, for some of whom the right thing will be just to get themselves off the tracks altogether, far away from the hurtling trolley until its brakes are fixed.                        

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Friday, July 20, 2012

Early radical prostatectomy trial: Does it mean what you think it means?

Another study this week added to the controversy about early prostate cancer treatment. The press, as usual, stopped at citing the conclusion: Early prostatectomy does not reduce all-cause mortality. But the really interesting stuff is buried in the paper. Let's deconstruct.

This was a randomized controlled trial of early radical prostatectomy versus observation. The study was done mostly within the Veterans' Affairs system and took 8 years to enroll a little over 700 men. This alone should give us pause. Figure 1 of the paper gives the breakdown of the enrollment process: 5,023 men were eligible for the study, yet 4,292 declined participation, leaving 731 (15% of those who were eligible) to participate. This is a problem, since there is no way of knowing whether these 731 men are actually representative of the 5,023 that were eligible. Perhaps there was something unusual about them that made them and their physicians agree to enroll in this trial. Perhaps they were generally sicker than those who declined and were apprehensive about the prospect of observation. Or perhaps it was the opposite, and they felt confident in either treatment. We can make up all kinds of stories about those who did and those who did not agree to participate, but the reality is that we just don't know. This creates a problem with the generalizability of the data, raising the question of who are the patients that these data actually apply to.

The next issue was what might be called "protocol violation," though I don't believe the investigators actually called it that. Here is what I mean. 364 men were randomized to the prostatectomy group, and of them only 281 actually underwent a prostatectomy, leaving nearly one-quarter of the group free of the main exposure of interest. Similarly, of the 367 men randomized to observation, 36 (10%) underwent a radical prostatectomy. We might call this inadvertent cross-over, which does tend to happen in RCTs, but needs to be minimized in order to get at the real answer. What this type of cross-over does is, as is pretty intuitively obvious, blend the groups' differences in exposure, resulting in a smaller difference in the outcome, if there is in fact a difference. So, when you don't get a difference, as happened in this trial, you don't know if it is because of these protocol violations or because these treatments are essentially equivalent.

And indeed, the study results indicated that there is really no difference between the two approaches in terms of the primary endpoint (all-cause mortality over a substantially long follow-up period was 47% in the prostatectomy and 50% in the control groups [hazard ratio 0.88, 95% confidence interval 0.71 to 1.08, p=0.22]). This means that the 12% relative difference in this outcome between the groups was more likely due to chance than to any benefit of the surgery. "But how can cancer surgery impact all-cause mortality?" you say. "It only claims to alter what happens to the cancer, no?" Well, yes that is true. However, can you really call a treatment like that successful if all it does is give you the opportunity to die of something else within the same period of time? I thought not. And anyway, looking at the prostate cancer mortality, there really was no difference there either: 5.8% attributable mortality in surgery group compared to 8.4% in the observation group (hazard ratio 0.63, 95% confidence interval 0.36 to 1.09, p=0.09).  

The editorial accompanying this study raised some very interesting points (thanks to Dr. Bradley Flansbaum for pointing me to it). He and I both puzzled over this one particularly unclear statement:
...only 15% of the deaths were attributed to prostate cancer or its treatment. Although overall mortality is an appealing end point, in this context, the majority of end points would be noninformative for the comparison of interest. The expectation of a 25% relative reduction in mortality when 85% of the events are noninformative implies an enormous treatment effect with respect to the informative end points.
Huh? What does "noninformative" mean in this context? After thinking about it quite a bit, I came to the conclusion that the editorialists are saying that, since prostate cancer caused such a small proportion of all deaths, one cannot expect this treatment to impact all-cause mortality (certainly not the 25% relative reduction that the investigators targeted), the majority of the causes being non-prostate cancer related. Yeah, well, but then see my statement above about the problematic aspects of disease-specific mortality as an outcome measure.

The editorial authors did have a valid point, though, when it came to evaluating the precision of the effects. Directionally, there certainly seemed to be a reduction in both all-cause and prostate cancer mortality in the group randomized to surgery. On the other hand, the confidence intervals both crossed unity (I have an in-depth discussion of this in the book). On the third hand (erp!) the portion of the 95% CI below 1.0 was far greater than that above 1.0. This may imply that with a study that could have achieved greater precision (that is, narrower confidence intervals) we might have gotten a statistical difference between the groups. But to get at higher precision we would have needed either 1) a larger sample size (which the investigators were unable to obtain even over an 8-year enrollment period), or 2) fewer treatment cross-overs (which is clearly a difficult proposition, even in the context of a RCT), or 3) both. On the other hand (the fourth?), the 3% absolute reduction in all-cause mortality amounts to the number needed to treat of roughly 33, which may be clinically acceptable.

So what does this study tell us? Not a whole lot, unfortunately. It throws an additional pinch of confusion into the cauldron already boiling over with contradiction and uncertainty. Will we ever get the definitive answer to the question raised in this work? I doubt it, given the obvious difficulties implementing this RCT.  
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Tuesday, July 17, 2012

House appropriations bill to terminate AHRQ and prohibit funding patient-centered research

Update 7/18/12, 3:30 PM eastern:

The Hill has reported here that the bill has cleared the subcommittee. It will be going to the full committee next week.
The $150 billion bill cuts $6.3 billion from current levels of spending in the Labor, Health and Human Services and Education Departments and is part of Republican efforts to rein in government spending – an important message for the GOP on the campaign trail.
But other areas are slashed. The bill ends President Obama’s signature Race to the Top education initiative and cuts millions from advanced appropriations for the Corporation for Public Broadcasting, which funds NPR and PBS. The agency that monitors child labor abroad is cut by 68 percent and the agency that distributes Social Security payments gets cut by $764 million. It also would cut funding for Planned Parenthood if the organization continued to provide abortions.
(Hat tip to Michael Millenson for the above link) 

Yes, folks, you read that right: The House of Representatives has drafted an appropriations bill that will dissolve the AHRQ and prohibit any funding for patient-centered outcomes research (PCOR). The AHRQ is an agency that spearheads and funds healthcare safety and quality research, as well as ways to rein in the costs while expanding access. If it is eliminated, there will be no one to focus on these critical issues. This bill is truly anti-patient and the reps must be informed that they have gone too far.

Here are the names of the Appropriations Committee members, with the subcommittee members responsible for this bill in bold (via STFM):

Democratic Members

  • Norman D. Dicks, Washington
  • Marcy Kaptur, Ohio
  • Peter J. Visclosky, Indiana
  • Nita M. Lowey, New York
  • José E. Serrano, New York
  • Rosa L. DeLauro, Connecticut
  • James P. Moran, Virginia
  • John W. Olver, Massachusetts
  • Ed Pastor, Arizona
  • David E. Price, North Carolina
  • Maurice D. Hinchey, New York
  • Lucille Roybal-Allard, California
  • Sam Farr, California
  • Jesse L. Jackson, Jr., Illinois
  • Chaka Fattah, Pennsylvania
  • Steven R. Rothman, New Jersey
  • Sanford D. Bishop, Jr., Georgia
  • Barbara Lee, California
  • Adam B. Schiff, California
  • Michael M. Honda, California
  • Betty McCollum, Minnesota

  • Republican Members

  • Harold Rogers, Kentucky, Chairman
  • C.W. Bill Young, Florida
  • Jerry Lewis, California
  • Frank R. Wolf, Virginia
  • Jack Kingston, Georgia
  • Rodney P. Frelinghuysen, New Jersey
  • Tom Latham, Iowa
  • Robert B. Aderholt, Alabama
  • Jo Ann Emerson, Missouri
  • Kay Granger, Texas
  • Michael K. Simpson, Idaho
  • John Abney Culberson, Texas
  • Ander Crenshaw, Florida
  • Denny Rehberg, Montana
  • John R. Carter, Texas
  • Rodney Alexander, Louisiana
  • Ken Calvert, California
  • Jo Bonner, Alabama
  • Steven C. LaTourette, Ohio
  • Tom Cole, Oklahoma
  • Jeff Flake, Arizona
  • Mario Diaz-Balart, Florida
  • Charles W. Dent, Pennsylvania
  • Steve Austria, Ohio
  • Cynthia M. Lummis, Wyoming
  • Tom Graves, Georgia
  • Kevin Yoder, Kansas
  • Steve Womack, Arkansas
  • Alan Nunnelee, Mississippi
 Call yours at 202-225-3121!

Here are some pertinent links, courtesy of Kenny Lin, MD, and others:
-The House press release (note they brag about defunding ObamaCare and "protecting" life in the same breath)
-The draft of the bill (see page 90)
-AcademyHealth announcement (where I learned about the PCOR prohibition)
-Statement from Mary Wooley, the President of Research!America about why this is a stupid move
-The Incidental Economist blog is compiling a list of useful projects funded by the AHRQ here

So please please please call your reps to stop this insanity!

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Tuesday, July 10, 2012

DHHS: Does this lie make me look stupid?

Update, July 12, 4:30 PM Eastern:
Just got this extra lame reply from healthfinder:

Dear Ms. Zilberberg, Thank you for contacting  healthfinder is a government Web site featuring prevention and wellness information and tools to help you and those you care about stay healthy. At, you will find:
 ·         interactive tools like menu planners and health calculators
·         online checkups
·         printable information that you can share with a family member or take to the doctor. is coordinated by the Office of Disease Prevention and Health Promotion (ODPHP), U.S. Department of Health and Human Services and the National Health Information Center (NHIC). NHIC links people to organizations that provide reliable health information. All of’s topics and tools go through subject matter expert reviews. As a result of these reviews, sentences and wording sometimes get updated and/or changed. This particular topic has already been reviewed, and the content team will be rewording the language; the word “best” will be removed from that sentence. This change will be reflected on the site in the next scheduled update. Sincerely, TeamNational Health Information is coordinated by the Office of Disease Prevention and Health Promotion (ODPHP), U.S. Department of Health and Human Services and the National Health Information Center (NHIC).


Update July 11, 10:50 AM Eastern
I have just sent the following e-mail to at the address I urge everyone who reads this to send them the same or a similar message. And if you do, please, leave a comment below to let everyone know.
I wanted to let you know that the information you posted on this web page on Pap testing is erroneous and misleading. Telling women that the "best" way to prevent cervical cancer is through a regular Pap test is not supported by evidence. The "best" way is to prevent HPV infection by engaging in safe sexual intercourse. As a public health communicator you are doing a tremendous disservice to the public.  
I urge you to change this message to reflect reality. 
Thank you. 
Marya Zilberberg, MD, MPH, FCCP 

There is pounding in my temples, my back muscles are in a spasm, and I might even be turning green and busting out of my clothes. What caused all this? This innocent-looking tweet from the Department of Health and Human Services:

I had to do a double take. My blood started to boil almost immediately. But I persisted, clicked on the link, and saw this:

The first sentence really says "The best way to prevent cervical cancer is to get regular Pap tests." Jaw, meet floor. What does the word "prevent" really mean? I went to The Free Dictionary for enlightenment:

Just as I had suspected: to avert, to keep from happening. And how does a Pap test keep the cancer away? It finds "abnormal cells before they turn into cancer." And where do abnormal cells come from? God, right? Well, no, they are mostly associated with an HPV infection, which comes from exposing yourself to unprotected sexual intercourse, usually with someone whose HPV status you don't know. You see where I am going with this? The message here is that there is nothing more effective at preventing cervical cancer than having a Pap test to detect early changes and lop out the misbehaving piece of your cervix. Are they serious? Is this really the "best way"? Let's examine the meaning of "best":

I guess beauty (and value) are in the eye of the beholder. Does subjecting yourself to a surgical procedure that may leave your cervix unable to help your uterus to maintain a pregnancy qualify as "surpassing all others in excellence" or as "most desirable"? Not in my book, not when a little advanced planning and a nickel for a condom could could keep that horse from leaving the barn in the first place. True prevention does not take place in a doctor's office, and it is a mistake to equate screening to prevention.

Come on, DHHS, who writes your stuff? Fire them! You are risking your credibility. What's next? "Bulimia is the best way to prevent obesity"?    

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Monday, July 2, 2012

Drugs and devices: expensive. Hubris: priceless.

This morning I was listening to the Morning Edition on NPR, and heard a story about the tax on medical devices that is written into the healthcare law. As you can imagine, there is opposition to such a tax by the manufacturers, as they are concerned about the usual, "stifling innovation" (yawn). It's hard to be amused by anything to do with healthcare these days, but here is a part of the conversation that had me in LOLZ (my 14-yo's expression):
ARNOLD: Okay. So here's how this new tax works. When a medical device gets sold, there will be a 2.3 percent sales or excise tax. Now, people who support this tax say that the medical device makers are exaggerating about the impact. Paul Van de Water is an economist with the left-leaning Center on Budget and Policy Priorities. He says that this tax is basically the same as a sales tax that you pay at the grocery store.
PAUL VAN DE WATER: The grocery store is collecting the tax. The grocery store is the institution that sends the tax to the state government, just the way the medical device manufacturer is going to write the check to the Treasury.
ARNOLD: Van de Water says that the tax doesn't really target the medical device makers that much. They'll just pass most of the cost along to their customers, who are mostly big hospitals, the same way a grocery store charges their customers. But the industry disagrees. David Nexon is with the medical device trade group called AdvaMed.
DAVID NEXON: There's a difference between a tax that, you know, an individual consumer pays as opposed to one that you're negotiating a price with a large, sophisticated buyer.
ARNOLD: In other words, Nexon says a hospital chain will push back and resist paying anything extra.
NEXON: In this very competitive market, it's extremely difficult for our members to raise prices.
Hah! Is he saying what I think he is saying? That because individual consumers are too dumb to understand about externalizing additional expenses, such as taxes, it is easier to put one over on them than on the savvy hospitals? Could he possibly mean that only "large, sophisticated buyers," and not ordinary consumers, would never stand for the information asymmetry they thrive on? That the individual consumers just don't have the power that hospitals do to push up against potentially predatory pricing? 

The last time I heard or read anything this blatant was in this New York Times piece from December 2009. This is a company executive talking about the rationale for the company's cancer drug's disproportionately steep price:
Mr. Caruso also said the price of Folotyn was not out of line with that of other drugs for rare cancers. Patients, moreover, are likely to use the drug for only a couple of months because the tumor worsens so quickly, he said. So the total cost of using Folotyn will be less than for many other drugs with lower monthly prices.
Wow, do these people get paid to advance their organizations' agendas? For my money they are not doing such a hot job at anything other than confirming all the societal views of them. Are they too stupid to realize that, even if you think stuff like this, you shouldn't say it out loud? How embarrassing.

Bottom line? Their drugs and devices: expensive. Their hubris: priceless.

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