ACR-FDA Summit Focuses on Study Design, Safety Considerations

Researchers should also make sure to include a systematic plan to assess safety within a trial, just as they do for efficacy.

“A safety database with controlled data on 1,000 to 1,500 patients exposed to the proposed market dose of a new molecular entity for at least one year would be informative and feasible without the need for more patients,” Dr. Habal said. Use of pre-specified analyses for safety, particularly for adverse events of special interest, may also help address some of the uncertainties with data interpretation.

Data Sources to Assess Safety

Dr. Curtis

When choosing the right data sources to assess safety, researchers may consider electronic health records (EHRs) or claims data, among other options. Each option comes with its own benefits and challenges, said Lesley Curtis, PhD, chair of the Department of Population Health Sciences, Duke University, Durham, N.C. The decision requires thinking about the purpose for each data source, how rich the data may be for a study’s purpose and the challenge of data standardization.

EHRs from a single health system may appear useful on the surface but can be limited. “We may not have the complete picture of that patient’s healthcare encounters,” Dr. Curtis said.

EHRs from a single health system typically capture 50% or more of patient encounters for fewer than 30% of patients, she said. This may not be an issue for patients with stable health data but exposures and outcomes that are occurring in different healthcare systems aren’t being captured and will affect study outcomes.

Additionally, such data as demographics and procedures may be standardized within EHRs, but vitals, lab results and symptoms may not be easy to come by. This can be true even if natural language processing is used to go through the data.

By comparison, claims data from a private or public insurer may have better structured, standardized data. However, reimbursement can influence coding, and clinical detail may be limited.

Claims data from private or public insurers may also be incomplete. “About 15% of individuals change health insurance in a given year, and 20% or more spend one month uninsured each year,” Dr. Curtis said. Each year, for example, about 25% of Medicaid beneficiaries change coverage or experience a gap in coverage. All of this can lead to data gaps.

Combining data from EHRs and insurance claims may seem like a reasonable way to try to address these limitations. However, with the exception of Medicare data for those 65 and older, the reality is much more complex, Dr. Curtis said.