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