Patient-centered research: answering the questions that matter to people

“Large investments are too often made in studies that provide poor-quality evidence,^1​ are overtly biased,² are not applicable to most patients,^3​ or yield results that do not address the real concerns of individuals facing clinical decisions.^4,5”  [1] (Patient Centered Outcomes Research Center, JAMA, April 18, 2012)

Indeed. This is not only “too often”, it is in fact characteristic of most research, whether sponsored by the National Institutes of Health (NIH), foundations, or private companies. The reasons for this are that it is easier to do and it relatively well funded (thus the “large investments”).

Many years ago, researchers, particularly those providing primary care, distinguished between “disease-oriented evidence” (DOEs) and “patient-oriented evidence” (POEs, or later, adding “that matters”, POEMs). The first is about showing that a treatment improves a disease. The second is looking at what treatments improve the life of a person. There is a big difference. A simple example might be in looking a regimen for diabetes that minimizes the complications from high blood sugar by keeping the average blood sugar much lower than had previously been the goal (called “tight control”). Disease-oriented evidence might show that using frequent insulin injections to keep the blood sugar in the low-normal range reduces the long-term negative effects of diabetes. A patient-oriented approach, however, looks at the overall impact on the person, not just the disease. Does the patient find it difficult to administer more frequent injections of insulin and check their blood sugar? Do they spend a significant amount of time with blood sugar that is in fact too low (after all, reducing the average increases the probability that sometimes it will be too low), and feel fuzzy-headed and unable to live the lives they wish to? Or feel dizzy? Or that a certain percent actually pass out from low blood sugar? Maybe break their hips and end up in the hospital or even dying from its complications? Even though their diabetes is in “good” control? “The disease was controlled but the patient died from a complication of treatment” is not a desirable patient-oriented outcome!

The motivation for private companies, most often pharmaceutical companies, to fund disease-oriented research is fairly obvious. Their sole agenda is to make profit, so they are interested in supporting research that shows that their drugs are effective for treating certain conditions. They have a number of advantages in this arena:

·         Showing “effectiveness” requires, by FDA criteria, only to show that a new drug or other treatment is more effective than placebo, not than the currently available treatments;

·         Since they are paying for it, they can suppress the publication of results that do not show their drugs in a good light;

·         They have to show only that it modifies the disease, not that it is the best choice for any individual patient (thus it is Disease-oriented, rather than Patient-oriented);

·         In lieu of patient-centered research, they have huge marketing budgets (far in excess of their research budgets) to advertise their products to both providers and directly to patients once they have been approved by the FDA.

Why NIH would mostly fund this sort of research is more complicated. Part of it is that an entire industry has been built around doing disease-oriented research, largely in biological science laboratories, but also in doing clinical trials in people. Thousands of academics and the institutions at which they work are dependent upon such funding to maintain and advance their careers and institutions. The review committees that make recommendations to approve or disapprove funding are “peer” committees, made up of people who do, largely, the same kind of work. This is good because they can understand and evaluate the science involved (a really bad thing would be for a group of politically-appointed ideologues to make the decisions, and this sometimes has occurred), but they are limited by their understanding of how research is done and what its goals should be. This relates to a second challenge – patient-oriented research is more complicated, more difficult to do, and leads to less “clear” outcomes. Of course, it is more relevant to patients and their providers making decisions about their care, but it is harder to fit into a rigid research model in which all but one variable is tightly controlled. This can lead to research that is done because it is possible to do it, rather than because it answers the questions that we have (see “Defining Streetlight Research”, February 26, 2009). Most traditional NIH researchers have no objection to patient-oriented research, but in an era of limited funding availability might be quite concerned if funding it decreased the amount available for the kind of work that they do.

Trying to address this, the Affordable Care Act of 2010 established the Patient-Centered Outcomes Research Institute (PCORI) to apply the rigorous standards of Clinical Effectiveness Research (CER) to treatment of patients, not diseases. One clear need here is that people, particularly older people, often have more than one disease. The “right” treatment for a patient’s cancer needs to take into account its effect on his/her diabetes – or heart disease, hypertension, arthritis, depression, alcoholism, glaucoma, poverty, and yes, maybe, another cancer – in any or all combination. Because we care for the person, who may have any or all of these conditions, primary care doctors are likely to be more sensitive to these interactions than are physicians caring for only one of them. It is for this reason that we have advocated for a National Center for Primary Care to look at the comprehensive care of patients differently than the existing disease-oriented Centers (e.g, the National Cancer Institute, the National Center for Heart, Lung and Blood Disorders, the National Institute of Mental Health) have.

The article in the April 18, 2012 issue of JAMA from which the opening quotation is drawn, “Methodological Standards and Patient-Centeredness in Comparative Effectiveness Research”, includes the following case as an example:

“A 78-Year-Old Man with Heart Failure, Diabetes, and Renal Failure. Mr B was admitted to his local hospital for the fourth time this year. Mr B experienced symptoms of shortness of breath and weight gain that led him to contact his physician, who recommended another hospitalization. He lives with his wife in a 2-story house located 30 miles from the hospital. He has recently been unable to climb the stairs to his bedroom. Mr B requires outpatient hemodialysis 3 times per week, but missed his last dialysis treatment because he felt too tired to go. This is his second hospital admission after missing a dialysis appointment. After each admission, Mr B received standard discharge instructions on how to care for himself at home. Mr B's highest priority is his independence, including the ability to drive and to remain in his own home.”

To make appropriate decisions about Mr B’s care requires not only considering the interplay of his several chronic diseases, but the circumstance of, and his own preferences and goals for his life. This cannot be done by employing solely the findings of disease-oriented research.

PCORI is not a National Institute for Primary Care, but it may help to achieve some of the same goals. In the same issue of JAMA, Joe Selby (the director of PCORI) and colleagues list the both the statutory criteria for PCOR-funded research:[2]

1. Effect on the health of individuals and populations
2. Probability of improvability through research
3. Inclusiveness of different populations
4. Current gaps in knowledge/variation in care
5. Effect on health care system performance
6. Potential to influence decision making
7. Patient-centeredness
8. Rigorous research methods
9. Efficient use of research resources

and their proposed priorities for national research:

1. Assessment of options for prevention, diagnosis, and treatment
2. Improving health care systems
3. Dissemination and communications research
4. Addressing disparities
5. Accelerating patient-centered outcomes research and methodology

None of these are disease specific, although unquestionably much of the research that is funded by PCORI will look at people with specific diseases. These criteria, however, recognize the need for treatment plans to take into account all aspects of a person, and by extension the family and community of which they are a part. This includes addressing the disparities that exist between groups, especially poor and minority groups; that is to say, addressing issues of social determinants of health and social injustice.

Maybe we will finally get funding for studies that provide us will more useful information for caring for actual people.

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[1] Methodology Committee of the Patient Center Outcomes Research Institute, “MethodologicalStandards and Patient-Centeredness in Comparative Effectiveness Research”, JAMA, 2012;307(15):1636-1640. doi: 10.1001/jama.2012.466.

[2] Selby JV, Beal AC, Frank L, “The Patient-Centered Outcomes Research Institute (PCORI) National Priorities for Research and Initial Research Agenda”, JAMA 2012;307(15):2583-4. Doi: 10.1001/jama.2012.500

"Eggs Benedict" and "Choosing Wisely": often the best thing to do is nothing

Years ago (OK, decades ago), when Woody Allen was a standup comic, he did a short, famous bit called “Eggs Benedict”. The narrator (let’s say “Woody”) is having pain in the chestal area (a great formulation which has long been popular in my house). He is pretty sure it is heartburn, but is worried and doesn’t want to pay the $25 to see a doctor (I told you it was a long time ago). Luckily his friend, Eggs Benedict, is having the same kind of pain. He figures if he can get Eggs to go to the doctor, he can find out what it is and save money. It works, and Eggs finds out it is heartburn. Two days later, he discovers Eggs is dead. He immediately checks into the hospital, has all kinds of tests, and discovered he has – heartburn. The bill is $110 (it was a really long time ago!) He goes to see Eggs’ mother and asks if his friend suffered much. “No,” she says, “the car hit him and that was it!”

I was thinking about this story when I was asked to call into a local radio talk show to comment on “Choosing Wisely”, an initiative of the American Board of Internal Medicine (ABIM), which calls on medical specialty societies to list 5 tests or treatments frequently performed in their specialty that they recommend not be done, or not be done on most patients. In the recently released report, 9 medical specialty societies are represented, for a total of 45 recommendations, which can be found here. The 5 for my own specialty, Family Medicine, listed by the American Academy of Family Physicians’ (AAFP), were:

1.  Don’t do imaging for low back pain within the first six weeks, unless red flags are present.

2. Don’t routinely prescribe antibiotics for acute mild-to-moderate sinusitis unless symptoms last for seven or more days, or symptoms worsen after initial clinical improvement.

3.  Don’t use dual-energy x-ray absorptiometry (DEXA) screening for osteoporosis in women younger than 65 or men younger than 70 with no risk factors.

4.  Don’t order annual electrocardiograms (EKGs) or any other cardiac screening for low-risk patients without symptoms.

5. Don’t perform Pap smears on women younger than 21 or who have had a hysterectomy for non-cancer disease.

Each is backed by the evidence, and is accompanied by a summary of the reasons. For example, for #2: “Most sinusitis in the ambulatory setting is due to a viral infection that will resolve on its own. Despite consistent recommendations to the contrary, antibiotics are prescribed in more than 80 % of outpatient visits for acute sinusitis. Sinusitis accounts for 16 million office visits and $5.8 billion in annual health care costs.” Big money for a treatment that doesn’t work, and can cause bad side effects (allergies to the antibiotics and increased resistance of bacteria to antibiotics, for two).

The talk radio hosts had questions, especially about treatment of cancer. One of the American Society of Clinical Oncologists’ (ASCO) recommendations is “Don’t use cancer-directed therapy for solid tumor patients with the following characteristics: low performance status (3 or 4), no benefit from prior evidence-based interventions, not eligible for a clinical trial, and no strong evidence supporting the clinical value of further anticancer treatment.”  That seems like a no-brainer to me, but they wanted to know “What if a patient wants treatment for cancer anyway?” I said I thought it was the responsibility of the doctor to point out that the treatment would not help, and would not only cost money but would have a lot of toxic side effects; I said that I thought most people, if they knew they were going to die from their cancer and the treatment would not help, would not wish to spend their last days and weeks nauseated, losing their hair, and being unable to interact comfortably with their loved ones.

The radio hosts also said “We are always told patients should be self-advocates. What if advocating for ourselves we say we want antibiotics for our sinusitis?” I said that self-advocacy was really important, because no one but the patient and their family could really identify what their health goals were. But this was different from deciding what treatment you wanted; going to the doctor is not going to the grocery store with your shopping list that may include both healthful and bad-for-you foods. It is critical that you identify where you want to go and work with the doctor, or other provider, to come up with a plan that is mostly likely to get you there safely and effectively.

Coincidentally, the same week I facilitated the discussion about futile treatment at the end of life for a group of third-year medical students in their medical ethics course. They had just received a lecture from a distinguished medical oncologist, who presented the four core principles of medical ethics: Autonomy, Beneficence (do good), Non-maleficence (do no harm), and Justice. They also read several articles documenting cases in which end of life decision-making did not go smoothly or well, and the article “How Doctors Die” by Ken Murray, that I have previously discussed (How people die, and how should we?, April 7, 2012). One of the cases involved a patient with terminal cancer who had already failed treatment, and for whom further treatment would be futile (although not without adverse effects). He had agreed to hospice, and to comfort care, until a relative (a physician!) came to town and demanded additional treatment for him, and convinced him to as well.

The medical students, who had  all been through clinical experiences and most of whom had been part of teams that confronted dealing effectively with dying patients, were in agreement with the physician in the article, and with each other, that the treatment was futile and would be a bad idea. However, several felt that, if the patient demanded it, the principle of Autonomy required that it be given. Others noted that this might violate the principle of Non-maleficence. I pointed out that that there were many areas in which we do not allow the patient to pick his/her treatment of choice. For example, we do not allow people to walk into a pharmacy and buy narcotic pain relievers without a prescription, no matter how much they might want them. Certainly the effects of chemotherapy poisons were at least as great.

These are not always easy decisions, but it is one of the reasons being a doctor is hard, respected, and well-paid. If everything were a simple algorithm and one could just memorize the right answer as these medical students were expected to do so often on their multiple-choice tests, it could be done by someone with much less training. Sure, it is possible that someone getting antibiotics for viral sinusitis to get better – indeed they usually do, with our without the antibiotics. Temporal association is not cause. Thus, even when you do the right thing, based on the evidence, and do not get a test or treatment, it is still possible that you will end up worse.

As Eggs and Woody discovered.

How people die, and how should we?

On January 4, 2012, "How Doctors Die"; post on Zocalo Public Square by Ken Murray, I called attention to “How doctors die: it’s not like the rest of us, but it should be” a very articulate discussion by Dr. Murray about how the physicians he knows generally eschew “heroic” interventions at the end of life. This is because they know how futile, and often painful, such interventions can be and how disruptive they can be of the little time that they have left. Physicians know more than most other people about what is likely to work and what is not; they also know more about what is likely to just cause discomfort. I hope that Dr. Murray’s article will be widely read by both the physicians who make recommendations for patients at the end of life and the non-physician public who make decisions about what they want for themselves and their loved ones.

A version of Dr. Murray’s piece later appeared in the Wall St. Journal on February 25, 2012 with the headline “Why Doctors Die Differently”. It is discussed by Dr. Kenny Lin in his blog, Common Sense Family Doctor, “Addressing gaps in end-of-life planning”, March 15, 2012. Dr. Lin focuses on the important issue of “advance directives”, which includes Living Wills and Durable Powers of Attorney for Health Care (DPOAs), mechanisms through which people can help to ensure that their wishes for how they want to be treated – or not treated – at the end of their lives are honored, even when they themselves are not able to make specific decisions. A DPOA designates one person – one with whom, hopefully, you have had serious discussions about what you really want – to be your decision maker. This is very important; while under the law spouses have the right to make decisions, when there is no spouse and are multiple adult children there is no provision for who decides other than DPOA. There is no provision for a majority vote. While it is always best if everyone in the family agrees on a course of action, it doesn’t always happen. There may be several children in agreement, and one who wants something different. Sometimes this ends up in court, with a judge deciding. This is not the best scenario, which is why there should always be a DPOA. It does not solve every problem, but it definitely helps to have a specified decision maker. This issue is also addressed, from a patient and family perspective, in a recent NY Times Op-Ed by Sylvia Jacoby, Taking responsibility for death (March 31, 2012).

Such planning, however, requires thinking about hard issues. You have to decide if you want to have cardiac resuscitation if your heart stops, or be placed on a ventilator (breathing machine) when you can’t breathe on your own, or be “fed” through your vein when you can’t eat. These are all legitimate medical interventions that can have real value when there is an acute problem that is likely to be reversed (someone is temporarily unable to eat or swallow, or breathe on their own, but are likely to be able to in time). Cardiac resuscitation, which involves electric shocks and chest compressions, contrary to what you see on TV shows, hardly ever “works” when applied to people at the end of life whose body is in the process of dying, if by “work” one means a reasonable period of survival. It sometimes gets the heart re-started, but most of the time it happens again. A small percent of people who receive this treatment leave the hospital, and very few are back to “normal”. It is great to do for healthy younger people who have an episode of trauma (like on TV) but is unlikely to have benefit for folks at the end of life.

So why do we do it? Not only cardiac resuscitation, but so many other interventions that are of little or no benefit, especially when the body is suffering from the failure of multiple organ systems. And when, as indicated by Murray and Lin and many others, it is not what doctors want for themselves? As usual there are many reasons. Part of it is that doctors are, by and large, trained to do “whatever can be done” if there is “a chance”. However, a chance of what? This is a big question. To stay “alive” but unaware of one’s surroundings (from dementia, coma, or both), on a ventilator, and often in pain, for a few days, hours or minutes?  Even when doctors think about this issue, they often worry that if they don’t do something, they may be criticized, or even sued, by the patient’s family; they tend to go with the idea that doing something is always safer (from this point of view) than doing nothing.

The whole field of palliative care exists to help people and their families get through the inevitable process of dying with dignity, but there are far too few palliative physicians relative to the number of doctors trained to “do something”. Years ago, a co-worker’s elderly mother was dying in the intensive care unit (ICU). I went to visit. The woman was very far gone and unable to understand anything; the family, several adult children, was being asked to give permission for a fairly invasive procedure. They had been told it might “help”, and asked me what I thought. I was pretty sure it wouldn’t, but first checked with the doctor to see how he thought it would. I then spoke with the family and asked what “it might help” meant to them. They said that they hoped that it would make her “better”. I asked if this meant that she might become conscious, alert, maybe be able to talk with them, maybe be able to say goodbye one last time before she died? Yes, that is what they meant. I gently explained that this procedure might help correct some laboratory values, but that there was no way it was going to make her “better” in the way they hoped, although there was a good chance that she would still experience the pain associated with doing it. They opted not to have it.

Why didn’t the doctor make this clear to them? Perhaps it was because he was young, and wanted experience doing the procedure, and really thought that making lab tests better was “helping”. (There is an old joke that at Harvard students and residents were always pressured to make sure their patients had normal laboratory tests; the patient might die, but it was critical that they did so with their electrolytes in “perfect Harvard balance”.) Perhaps he had been trained to always “do something”. Perhaps he saw this large, hovering family and was concerned that they would be upset, might sue, if he didn’t.

Or perhaps he didn’t know how to talk to them. Is there a social justice issue here? After all, death comes to everyone, and as Dr. Lin points out, advance directives are important for all people to have, not just members of communities that have suffered health disparities. But often the social class or ethnic difference between doctors and patients makes communication more problematic, makes it harder for doctors to know how to best address what are already difficult issues, makes patients’ families suspicious of whether a treatment being offered is “research” being done on someone because they are poor or minority, or, alternatively, whether a treatment is not being offered for the same reasons.

I have cared for many people who were dying but whose families wanted more done. People who already had advanced dementia and whose physical bodies were falling apart. People whose heart and kidneys and lungs were failing, who couldn’t swallow and might choke on even a small amount of food, but whose families believed that if we didn’t do a surgical procedure to poke a hole directly into their stomach we would be starving them; who thought that if we didn’t plan to do cardiac resuscitation or given antibiotics for a possible pneumonia, that we would be killing them. Sometimes I am able to point out that death happens to everyone, and that having your heart just stop, or having pneumonia, or not being fed, are relatively easy painless and natural ways to die. Sometimes I am believed and sometimes not.

While there are, of course, times when a family member is truly “crazy”, paranoid or delusional, a more common issue is that they are just acting out their guilt. The stereotype (because it often happens) is the “son from California”, who flies in at the end of life, has usually not been involved in the care of his parent for years while a sibling (usually a sister) was doing all the work, and who now wants “everything done”. (A really good reason for one person to be designated DPOA.) But sometimes there is simply a trust issue, not being sure that the doctor, especially one from a different class, race or ethnic background, is really treating their parent with the respect that they deserve, with the respect they would give to one of their own family members.

Perhaps if more people understood what Dr. Murray is saying about what it is doctors really want for themselves and their families, or if their doctors took the time and energy and effort to explain it to them, folks would be more able to believe and accept it when the best course is not to do any more.