I. Collecting New Primary Data

It is beyond the scope of this document to describe the planning, design, and conduct of clinical trials, observational studies, and other investigations for collecting new primary data. There is a large and evolving literature on these subjects (Friedman 2010; Piantadosi 2005; Spilker 1991). Also, there is a literature on priority setting and efficient resource allocation for clinical trials, and cost-effective design of clinical trials (Antman 2012; Chilcott 2003; Claxton 1996; Detsky 1990; FDA Adaptive Design 2010).

As noted above, the process of compiling evidence for an assessment may call attention to the need for new primary data. An assessment program may determine that existing evidence is insufficient for informing the desired policy needs, and that new studies are needed to generate data for particular aspects of the assessment. Once available, the new data can be interpreted and incorporated into the existing body of evidence.

In the US, major units of the National Institutes of Health (NIH) such as the National Cancer Institute (NCI); the National Heart, Lung, and Blood Institute (NHLBI); and the National Institute of Allergy and Infectious Diseases (NIAID) sponsor and conduct biomedical research, including clinical trials. The Department of Veterans Affairs (VA) Cooperative Studies Program is responsible for the planning and conduct of large multicenter clinical trials and epidemiological studies within the VA. This program also works with the VA Health Economics Resource Center to perform economic analyses as part of its clinical trials. The Food and Drug Administration (FDA) does not typically conduct primary studies related to the marketing of new drugs and devices; rather, it reviews primary data from studies sponsored or conducted by the companies that make these technologies. The FDA also maintains postmarketing surveillance programs, including the FDA Adverse Event Reporting System on adverse events and medication error reports for drug and therapeutic biologic products, and the MedWatch program, in which physicians and other health professionals and the public voluntarily report serious reactions and other problems with drugs, devices, and other medical products.

In the US, the Patient-Centered Outcomes Research Institute (PCORI) was established as an independent research institute by Congress in the Patient Protection and Affordable Care Act of 2010. PCORI conducts CER and related research that is guided by patients, caregivers and the broader health care community. PCORI’s five national research priorities are: assessment of prevention, diagnosis, and treatment options; improving health care systems; enhancing communication and dissemination of evidence; addressing disparities in health and health care; and improving CER methods and data infrastructure. PCORI devotes more than 60% of its research budget to CER, including for pragmatic clinical trials, large simple trials, and large observational studies, with the balance allocated to infrastructure, methods, and communication and dissemination research (Selby 2014).

Third-party payers generally do not sponsor clinical trials. However, they have long supported clinical trials of new technologies indirectly by paying for care associated with trials of those technologies, or by paying unintentionally for non-covered new procedures that were coded as covered procedures. As noted above, payers provide various forms of conditional coverage, such as coverage with evidence development (CED), for certain investigational technologies in selected settings to compile evidence that can be used to make more informed coverage decisions. Two main types of CED are “only in research,” in which coverage of a technology is provided only for patients with specified clinical indications in the payer’s beneficiary population who are enrolled in a clinical trial of that technology, and “only with research,” in which coverage of a technology is provided for all of the patients with specified clinical indications if a subset of those patients is enrolled in a clinical trial of that technology.

An early example of CED was the multicenter RCT of lung-volume reduction surgery, the National Emphysema Treatment Trial (NETT) conducted in the US, funded by the NHLBI and the Centers for Medicare and Medicaid Services (CMS, which administers the US Medicare program) (Fishman 2003; Ramsey 2003). In another form of conditional coverage known as conditional treatment continuation, payment is provided only as long as patients meet short-term treatment goals such as lowered blood cholesterol or cancer tumor response. In performance-linked reimbursement (or “pay-for-performance”), payment for a technology is linked to data demonstrating achievement of pre-specified clinical outcomes in practice; this includes schemes in which a manufacturer must provide rebates, refunds, or price adjustments to payers if their products do not achieve certain patient outcomes (Carlson 2010). Findings about the impact of conditional coverage, performance-linked reimbursement, and related efforts on coverage policies, patient outcomes, and costs are still emerging (de Bruin 2011).

Payers and researchers often analyze data from claims, electronic health records, registries, and surveys to determine comparative effectiveness of interventions, develop coverage policies, or determine provider compliance with coverage policies. These analyses increasingly involve efforts to link claims and other administrative sources to electronic health records and other clinical sources (Croghan 2010; de Souza 2012).

The ability of most assessment programs to undertake new primary data collection, particularly clinical trials, is limited by such factors as programs’ remit (which may not include sponsoring primary data collection), financial constraints, time constraints, and other aspects of the roles or missions of the programs. An HTA program may decide not to undertake and assessment if insufficient data are available. Whether or not an assessment involves collection of new primary data, the assessment reports should note what new primary studies should be undertaken to address gaps in the current body of evidence, or to meet anticipated assessment needs.