A methodological framework for tackling confounding by indication when assessing the treatment effects of Chinese herbal injections in the real world

AIM: In the context of integrative medicine, whether Chinese herbal injections are effective in routine practice has become a question of broad interest. However, confounding by indication (i.e., indication bias) is a prevalent and highly challenging methodological issue when using routinely collected health care data to assess the real‐world effectiveness of Chinese herbal injections. METHODS AND RESULTS: We proposed a methodological approach to tackling confounding by indication in assessing the real‐world effectiveness of Chinese herbal injections, incorporating empirical experiences, a literature review and interactive discussions, and a panel of external experts to finally achieve a consensus. This approach consisted of three cohesive steps, including a full understanding of treatment patterns, construction of fair comparisons by identifying appropriate combination treatments and comparators, and using statistical methods to further control for confounding. In the investigation of treatment patterns, we proposed five domains to identify treatment patterns with Chinese herbal injections, and we offered five patterns of combination treatments to characterize how Chinese herbal injections are used in conjunction with other treatments. In constructing fair comparisons, we suggested the use of both nonuse and active comparators; given the diverse combination treatments, we developed six scenarios that may form fair comparisons. In the statistical analysis, we discussed five statistical models for controlling confounding by indication, including their pros and cons. We also included a practical example to illustrate the usefulness of the methodological approach. CONCLUSION: The proposed approach may serve as an effective tool to guide researchers to reliably assess the effectiveness of Chinese herbal injections in the context of integrative medicine.