When patients, clinicians, or other healthcare stakeholders raise a question that doesn’t already have an evidence-based answer, sometimes the dilemma can be best addressed with a new research study. But not always. In some cases, a careful look at results and data from already-completed research studies can more quickly provide reliable findings that patients and those who care for them can use.
A new PCORI initiative—our Evidence Synthesis Initiative—will take that approach, which our authorizing law calls on us to pursue. The program will include rigorous reviews of the best evidence available on topics of critical concern to patients and other healthcare stakeholders. The goal is to synthesize all relevant completed studies on a particular clinical question in order to provide evidence that is stronger and more certain than the results of each individual study. Under this initiative, we will also fund projects that reanalyze data from already-completed studies to discover which specific groups of patients gain the most or least benefit, or, conversely, are at greater risk for harms from an intervention. And once we have synthesized the evidence, we will disseminate it through products designed to meet the needs of our various stakeholders.
This initiative is the latest that we at PCORI have undertaken as part of our mission to make authoritative, relevant, useful information from comparative clinical effectiveness research (CER) available to help patients and those who care for them make better-informed healthcare decisions. It complements the hundreds of patient-centered research studies we’ve funded comparing how well different care options work, and for whom, given patients’ needs, circumstances, and preferences.
Meta-analysis of Lupus Treatment Options
If not treated early with strong medications, kidney disease caused by lupus can lead to kidney failure and the need for dialysis. Through a meta-analysis of 65 previously conducted studies, a PCORI-funded project has determined that immunosuppressive drugs (e.g., cyclophosphamide) are better than corticosteroids for treating kidney inflammation in patients with lupus. This meta-analysis finding can inform discussions between patients and physicians about medication use. The project team is now testing a decision aid that it developed incorporating the meta-analysis findings.
Project: Individualized Patient Decision Making for Treatment Choices among Minorities with Lupus
Principal Investigator: Jasvinder Singh, MBBS, MPH, University of Alabama at Birmingham
A Deep Dive into Diabetes Research
In a randomized clinical trial, randomization ensures the comparability of treatment groups. But there remain important differences between individuals in each treatment group that can dramatically affect the likelihood of any one individual benefiting from or being harmed by a therapy. A major diabetes prevention study, including thousands of participants, had found that the drug metformin reduced the progression from prediabetes to diabetes. But when PCORI-funded researchers reanalyzed the study data, classifying participants more selectively according to how likely they were to develop diabetes, they found that the highest-risk participants received the greatest benefit and participants at lowest risk didn’t benefit at all (while still facing potential side effects from the drug).
Project: Assessing and Reporting Heterogeneity of Treatment Effect in Clinical Trials
Principal Investigator: David M. Kent, MD, MS, Tufts Medical Center Inc
Beyond Primary Research
Our Evidence Synthesis Initiative falls within our broader Research Synthesis program, which takes advantage of a wide variety of tools to pull together and analyze results for use by the public. The program includes PCORI activities already under way, such as our portfolio analysis and the topic nomination pathway that informs PCORI funding announcements. It will also branch out in new directions that will speed useful clinical information into stakeholders’ hands. Two of the approaches we plan to use are updating systematic reviews of the results of already-completed CER studies and reanalysis of data from such studies. These activities allow us to release products relatively rapidly within a set of clearly specified, rigorous, reproducible, and transparent methods.
Systematic reviews. The most common type of evidence synthesis is the systematic review. It provides answers to specific clinical questions by analyzing published and unpublished results from all relevant studies on a given topic. Systematic reviews identify, select, and summarize findings of available research to make clear what is known about a topic—and what is still not known. PCORI already has methodology standards for such reviews.
Systematic reviews often use statistical methods to combine published or unpublished study findings to produce estimates of an intervention’s effect and to illustrate how consistent and strong the effect is across the research. The most common approach is to use aggregate data meta-analyses, which typically summarizes the average treatment effect for each study population across all studies in the systematic review. One PCORI-funded study uses a variant of this method to compare treatments for kidney disease in patients with lupus (see box).
Based on input we have received from stakeholders, our initial efforts will include updated systematic reviews comparing treatment options for
- Atrial fibrillation
- Post-traumatic stress disorder
- Rheumatoid arthritis
- Urinary incontinence
We’ll implement this initial effort in coordination with the Agency for Healthcare Research and Quality.
Individual patient–level data (IPD) meta-analysis. Today, most research studies, including systematic reviews, provide the average result for the average individual—someone who may not actually exist. But by combining the granular specifics about each individual participant across several studies on the same topic, we have an opportunity to see how treatments may have different effects (i.e., greater benefit or greater harm) for individuals with different characteristics.
An IPD meta-analysis obtains and examines all of the relevant measured characteristics of each participant from all of the included studies in a systematic review. It can indicate whether treatments should be targeted for use in specific groups of individuals. It is also an important method to reconcile differences when studies examining the same treatments have conflicting results.
Other research data reuse opportunities. Besides IPD meta-analyses, a statistical approach called predictive analytics can be applied to previously conducted trials or other research data to provide more personalized results that can optimize the use of specific treatments. This approach can be helpful in studies with a diverse group of people and a wide range of individual responses to an intervention. An example of this approach is PCORI’s recently funded study on who benefits from diabetes prevention efforts (see box).
As our primary research results become available, our Dissemination and Implementation program will be working diligently to place individual study results into a context to best inform users. At the same time, our evidence syntheses will be important products to get into the public domain. Thus, the next question we face is: How would stakeholders prefer to receive this information?
To get a better focus on what would work best for a variety of healthcare decision makers, our Dissemination and Implementation program recently convened a stakeholder workshop. Participants included patients, clinicians, insurers, and employers. The participants expressed a strong need for brief and clear presentations of what evidence can be brought to bear on specific healthcare decisions, considering differing contexts and needs. They emphasized the importance of actionable information and tailoring findings to audiences. Finally, PCORI products should help patients and clinicians share in making health decisions.
All of us at PCORI are excited about evidence synthesis as an additional avenue for rapidly bringing useful evidence to patients, their families, clinicians, and other healthcare stakeholders. We look forward to sharing more details as our plans mature.
Editor's note: At the time that this blog post was published, Evelyn P. Whitlock, MD, MPH was PCORI's Chief Science Officer. She served in that role from September 2015 to June 2018.