Investigators Eye Gaps in Biosimilar Assessment Reports

August 31, 2020

Health technology tssessments play an important role in building confidence for use of biosimilars, yet very few meet criteria for thoroughness.

In an evaluation of health technology assessments (HTAs) for biosimilars, investigators found that the majority of HTAs lack systematic reviews of existing literature, appraisals of the quality of evidence, and cost analyses. The paper was published in Health Research Policy and Systems.

The authors concluded there is a substantial need for standard, minimum methodological criteria for the development of HTAs for biosimilars to help support public understanding of these agents and enable clinicians to “make more informed decisions about adopting biosimilars.”

Higher standards for HTAs would help to persuade health professionals who “are not convinced by expert opinion in regard to treatment interchangeability and substitution, and the perception that there is a lack of data in relation to efficacy and safety,” they wrote.

The authors identified 70 HTAs for biosimilars from their search of HTA organizations’ websites and noted that HTAs differed according to the extent and depth of information provided, which they said was one of the limitations of these reports. Based on previously established definitions, they classified 2 reports as full HTAs, 4 as mini-HTAs, and the rest—over 90%—as rapid reviews, “which gave no information regarding any evidence synthesis method.” The authors cited a previous review that reported rapid reviews are now the most frequently produced type of HTA and that HTA agencies use widely varying methodologies for compiling these.

Inclusions and Omissions

“Approximately half of the rapid reviews did not appraise the risk of bias of primary studies or the overall quality of evidence,” the authors said. “All full HTAs and mini HTAs addressed organizational, ethical, social, and legal considerations.” Most full and mini HTAs included an assessment of switching and a discussion of biosimilar education.

The majority of biosimilars addressed in the HTAs were anticancer and immunomodulating agents, most commonly tumor necrosis factor—alpha inhibitors. Infliximab biosimilars were the most frequently assessed, accounting for about 25% of HTAs.

Most HTAs supported the adoption of the biosimilar assessed, and the majority were published recently—46 of the 70 between 2015 and 2018. The authors observed that few countries produce HTAs on biosimilars: About half of all rapid reviews came from a single agency in France, and all 4 mini-HTAs were produced by organizations in Canada.

Rapid reviews lacking key HTA components

The authors discussed what they saw as shortcomings of the majority of the HTAs, saying, “Although most reports have supported the adoption of biosimilars, these statements have often been based on reports lacking a systematic literature review and not considering economic issues.”

The authors evaluated each report based on whether they covered safety and effectiveness; economic analysis; financial impact; clinical evidence; quality of evidence; organizational considerations; and ethical, social, and legal considerations.

The 2 full HTAs met all criteria. All full and mini-HTAs included a systematic review of the clinical evidence, compared with just 3% of the rapid reviews. Almost half of rapid reviews failed to evaluate the risk of bias of studies or the overall quality of the evidence, the authors said. Although all full and mini-HTAs addressed ethical, social, and legal considerations, just 39% of rapid reviews did.

A budget impact analysis was conducted in 1 full HTA, 3 of 4 mini-HTAs, and less than 40% of rapid reviews. The authors found the lack of budget impact analyses concerning, because the majority of biosimilars assessed were anticancer agents, immunomodulators, and insulins, which “represent the 3 largest biologic therapy areas, worth $110 billion—over half of all biologic global revenue.” The authors viewed this as a missed opportunity for an HTA to lead to cost savings by making a cost-effectiveness argument for a biosimilar.

Incomplete discussion of biosimilar Issues

In addition to the general criteria for HTAs, the authors evaluated whether HTAs addressed issues of particular importance for biosimilars, such as immunogenicity, switching, and extrapolation to additional conditions. One of the 2 full-HTAs, all 4 mini-HTAs, and about 60% of rapid reviews assessed immunogenicity. Only 20% of rapid reviews discussed switching, 66% discussed extrapolation, and 22% “provided an educational approach about biosimilars to patients, clinicians, or pharmacists,” whereas all 4 mini-HTAs and 1 full HTA addressed all 3. The authors stressed these issues are important for HTAs to address.

The authors also stated that often the same biosimilar may be licensed under multiple commercial names, and that “this situation can cause confusion…and a duplication of work.”


Ascef BO, de Freitas Lopes AC, de Soárez PC. Health technology assessment of biosimilars worldwide: a scoping review. Health Res Policy Syst. 2020;18(1):95. doi:10.1186/s12961-020-00611-y