Learning from Clinical Data

PCORI’s mission is to fund research that will help patients and those who care for them make better-informed health and healthcare decisions. To do this, PCORI’s work must satisfy two criteria: it must be scientifically valid, so patients, clinicians and other decision makers can trust the information produced, and it must be generalizable, so the findings can be applied to the large majority of patients who face a specific decision or choice.

Achieving both of these aims usually requires a combination of studies that complement each other.

Complementing Traditional Randomized Controlled Trials

Traditional randomized controlled trials (RCTs) remain a gold standard for scientific rigor and internal validity and are well suited for comparing the clinical effectiveness of two or more alternative options, especially when differences are expected to be relatively small. However, RCTs also have drawbacks–they often fail to include the full range of patients who face the treatment choice, such as those at extremes of age or adequate numbers of patients with additional medical conditions. RCTs can also be expensive to conduct and require years to complete.

Thus, RCTs alone cannot provide timely, applicable evidence for all the questions facing patients and other stakeholders. Another source of evidence about clinical effectiveness is observational studies, research that uses data from patients as they receive customary clinical care. With the widespread adoption of electronic health records (EHRs), large amounts of clinical data, including treatment and outcomes information, are becoming available. Observational studies using very large databases created from EHRs, sometimes linked with registry data or claims databases, can provide outcomes information for the entire range of patients considered eligible for a treatment of interest.

Such information may be useful to the decisions that patients, caregivers, clinicians, payers, and others make daily. Nevertheless, there is considerable scientific debate about the validity of conclusions drawn from such observational studies.

How Observational Studies Fit Within a Broader Research Portfolio

PCORI plans to lead a conversation in the healthcare community about the conduct and use of observational studies as key elements, along with RCTs, of a research enterprise dedicated to improving patient care and outcomes. PCORI’s National Priorities for Research commit to advancing this field.  PCORI also has included guidance for improving observational study designs in its Methodology Standards.

To further explore these themes, PCORI sponsored an Institute of Medicine (IOM) workshop in Washington, D.C., on April 25 and 26. The event brought together researchers, industry representatives, and policymakers for a series of presentations and panel discussions addressing the role that observational studies can play in complementing RCTs and expanding the library of useful evidence available to the healthcare community. This evidence is the basis of a learning health system, which applies this, and other knowledge generated through the delivery of care, to continuously improve outcomes and value.

With its impressive roster of members who can lend their expertise, the IOM is a natural partner for PCORI’s efforts to improve observational research. For example, the workshop was co-chaired by two IOM members, Ralph Horowitz, MD, MACP, Senior Vice President for Clinical Evaluation Sciences at GlaxoSmithKline, and PCORI Executive Director, Joe Selby, MD, MPH. Several members of the PCORI Methodology Committee participated in the meeting.  You can find a description of the workshop, its agenda, and its attendees on the event web page.

Directions for Future Work

Several themes emerged from the workshop that will guide future work in this area:

• We need a research enterprise that addresses important healthcare questions efficiently and effectively. Both randomized clinical trials and observational studies need continued support. They are complementary, and each has an important role in improving healthcare decision making.
• Getting patients and other healthcare decision makers the evidence they need to make the best decisions requires ensuring that the research questions are pegged to their needs.
• Observational research will benefit greatly from close engagement with the healthcare systems from which the datasets are built. Active participation by the healthcare systems will help these studies succeed and ensure that patients are respected throughout the process.
• To make the findings reliable and relevant to patients, the data used in observational research must be high quality and include patient-centered outcomes.

Observational research has the potential to detect differences in treatment effectiveness in patient subgroups with various characteristics and thus to develop predictions of how individual patients, with their unique sets of characteristics, will respond to specific treatments. PCORI is taking steps to build capacity to conduct such research.

One example is a major push to establish a national infrastructure built on clinical data in large patient populations. This infrastructure will support large-scale observational research as well as provide a starting point for RCTs based within healthcare systems. PCORI released two funding announcements totaling more than $68 million and a subsequent Request for Proposals to support the development of a National Patient-Centered Clinical Research Network and a coordinating center to support its operations. This ambitious effort will rely on health systems, clinicians, and patients to direct the network’s development.

Letters of intent (LOIs) from those interested in this opportunity are now under review. A subset of those LOIs will be approved, and those who submitted them invited to submit a full application. Awards are to be announced in December. PCORI also is pursuing opportunities to promote high-quality observational research to address the choice of treatments for individual diseases. As one of these prospects, PCORI’s Board of Governors identified uterine fibroids as an important clinical condition for which research gaps could be met through new sources of clinical data.

PCORI will work with the Agency for Healthcare Quality and Research to issue a funding announcement for development of a large prospective registry of women who have undergone one of several alternative procedures to treat symptomatic uterine fibroids. The funding will provide support for a group of observational studies that compare these treatments. PCORI plans to invest approximately $20 million in this program, and we expect it to provide valuable new insights to help women make informed choices.

By creating a data-rich network and promoting greater use of observational studies within a broader research portfolio, PCORI expects to produce high-quality evidence that will benefit all Americans.

* Note: When this blog post was published, Grossman was the Senior Program Officer at the Institute of Medicine (IOM) and one of the organizers of the PCORI-sponsored IOM workshop on observational studies.