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Aim: Health technology assessment (HTA) and payer organizations are often faced with early decision-making in oncology. To design and conduct robust indirect treatment comparisons (ITCs), it is important to better understand HTA and payer decision-maker perceptions of ITCs. Here we aim to describe what individuals with HTA and payer experience see as the acceptability of ITCs for HTA and payer organization coverage and reimbursement decision-making. Materials & methods: This survey included 30 current and former HTA and payer decision-makers from five countries: Australia, France, Germany, the UK (n = 5 each) and the US (n = 10). Main outcomes included the ratings of acceptance of ITCs and the presence of well-defined methodological guidance for ITCs. Results: ITCs are generally accepted by participants in Australia and the UK but are more likely evaluated on a case-by-case basis in France, Germany and the US. Four of five participants in Germany and the UK, two of five in Australia and one of five in France reported that well-defined and prescribed criteria regarding the use of ITCs were in place. Conclusion: There is a need for harmonization of methods used to assess ITCs by HTA and payers, especially in the rapidly evolving treatment landscape in oncology.

Failure to adjust for effect modifiers (EMs) in indirect treatment comparisons (ITCs) can produce biased and uncertain effect estimates. This is particularly important for health technology assessments (HTAs), where the availability of new treatments is based on comparative effectiveness results. Much emphasis has been placed on advancing ITC methods to adjust for EMs, yet whether EMs are appropriately identified for the conduct of ITCs in the first place is unclear. To understand the extent of guidance and requirements for the selection of EMs for ITCs currently available and if and how this guidance is applied in practice, a series of pragmatic reviews of guidance documents from HTA and non-payer organizations, primary published ITC analyses, and prior HTA submissions in two indications (non-small cell lung cancer and psoriasis) was conducted. The reviews showed that current ITC guidance mainly focused on developing analytical methods to adjust for EMs. Some organizations, such as HTA bodies in the UK, France and Germany, recommended the use of literature reviews, expert opinion and statistical methods to identify EMs. No detailed guidance on the selection process or the appropriate literature review approach was found. Similar trends were identified through the database search and review of prior HTA submissions; only few published ITCs and submissions included information on the EM selection process which was either based on findings from the literature, trial subgroup analyses, or clinical input. No reference to a systematic selection approach was found. There is an urgent need to fill the guidance gap identified across the reviews by including a step in ITC guidelines on how EMs should be identified through systematic reviews, formal expert elicitation, and a quantitative assessment of the EM distribution. Researchers and manufacturers are also encouraged to improve transparent reporting and justification of their selection of EMs to allow for an independent review of the set of factors being considered for adjustment. Both will contribute toward reducing bias in the ITC results and ultimately increase confidence in decision-making.

Simple Summary: There is an urgent need to develop new treatments for patients with relapsed/refractory multiple myeloma (RRMM) to address unmet medical needs. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel approach with the potential for long-term disease control. Ciltacabtagene autoleucel (cilta-cel) is a CAR-T treatment studied in patients with RRMM in the CARTITUDE-1 clinical trial and has shown clinically important effects. However, CARTITUDE-1 was a single arm study. The current study compared outcomes for cilta-cel with an external cohort of German patients that are similar to the ones in CARTITUDE-1 to compare the effectiveness of cilta-cel versus established clinical practice. To overcome potential bias, individual patient data were used to adjust for the differences in patient characteristics between cohorts. The results showed substantially better outcomes for cilta-cel on both overall survival and the time to next treatment. These findings highlight cilta-cel's potential as a novel, effective treatment to address unmet treatment needs. Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed/refractory multiple myeloma (RRMM). As cilta-cel was assessed in the single-arm CARTITUDE-1 clinical trial, we used an external cohort of patients from the Therapie Monitor registry fulfilling the CARTITUDE-1 inclusion criteria to evaluate the effectiveness of cilta-cel for overall survival (OS) and time to next treatment (TTNT) vs. real-world clinical practice. Individual patient data allowed us to adjust the comparisons between both cohorts, using the inverse probability of treatment weighting (IPW; average treatment effect in the treated population (ATT) and overlap population (ATO) weights) and multivariable Cox proportional hazards regression. Outcomes were compared in intention-to-treat (HR, IPW-ATT: TTNT: 0.13 (95% CI: 0.07, 0.24); OS: 0.14 (95% CI: 0.07, 0.25); IPW-ATO: TTNT: 0.24 (95% CI: 0.12, 0.49); OS: 0.26 (95% CI: 0.13, 0.54)) and modified intention-to-treat (HR, IPW-ATT: TTNT: 0.24 (95% CI: 0.09, 0.67); OS: 0.26 (95% CI: 0.08, 0.84); IPW-ATO: TTNT: 0.26 (95% CI: 0.11, 0.59); OS: 0.31 (95% CI: 0.12, 0.79)) populations. All the comparisons were statistically significant in favor of cilta-cel. These results highlight cilta-cel's potential as a novel, effective treatment to address unmet needs in patients with RRMM. [ABSTRACT FROM AUTHOR]