Emulation of a Target Trial to Evaluate the Causal Effect of Palliative Care Consultation on the Survival Time of Patients with Hepatocellular Carcinoma

Abstract

Palliative care has the potential to improve the quality of life of patients with incurable diseases or cancer, such as hepatocellular carcinoma (HCC). A common misconception of palliative care with respect to the patient’s survival remains a significant barrier to the discipline. This study aimed to provide causal evidence for the effect of palliative care consultation on the survival time after diagnosis among HCC patients. An emulation of a target trial was conducted on a retrospective cohort of HCC patients from January 2017 to August 2019. The primary endpoint was the restricted mean survival time (RMST) at 12 months after HCC diagnosis. We used the clone–censor–weight approach to account for potential immortal time bias. In this study, 86 patients with palliative care consultation and 71 patients without palliative care consultation were included. The adjusted RMST difference was −29.7 (95% confidence interval (CI): −81.7, 22.3; p-value = 0.263) days in favor of no palliative care consultation. However, palliative care consultation was associated with an increase in the prescription of symptom control medications, as well as a reduction in life-sustaining interventions and healthcare costs. Our findings suggest that palliative care consultation was associated with neither additional survival benefit nor harm in HCC patients. The misconception that it significantly accelerates the dying process should be disregarded.

Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials

“…We retrieved 3133 unique records, of which 200 were included in the review (Figure 1). All reasons for excluding records after full-text review are given in eAppendix 6 in Supplement 1.…”

“… The included studies spanned 26 fields of medicine, predominately infectious disease (43 [22%]; 27 [14%] on COVID-19), cardiology (30 [15%]), and oncology (30 [15%]) . One hundred and thirty-one studies (66%)…”

Comparative effectiveness of trimodal therapy versus definitive chemoradiation in older adults with locally advanced esophageal cancer.

“…Clone-censor-weight is a technique that has gained traction in the applied epidemiologic methods literature due to its handling of complex time-delimited (or sequential) interventions such as trimodal therapy. [137][138][139]190,[198][199][200][201] The data of each patient was cloned at first chemotherapy infusion within 120 days of cancer diagnosis and "assigned" analytically to both treatment strategies: trimodal therapy and definitive chemoradiation. When the observed treatment data of the patient was no longer consistent with the assigned treatment strategy, we analytically censored that observation.…”

Emulating an RCT in observational research in chest trauma: The target trial approach

“…3,7 Areas, which are likely more familiar to a surgical audience, include application of the target trial in organ transplantation, radical nephrectomy with or without lymph node dissection, colorectal cancer screening, and the effect of palliative care on patients with hepatocellular carcinoma. 1,[8][9][10] The authors of this review article are not aware of any publications in trauma using "target trial" concepts. The purpose of this article is to introduce the "target trial" to a trauma audience.…”

“…Hernán’s concept of a “target trial” was originally applied to research in areas, such as coronary heart disease, oncology, and analysis of large health databases 3,7 . Areas, which are likely more familiar to a surgical audience, include application of the target trial in organ transplantation, radical nephrectomy with or without lymph node dissection, colorectal cancer screening, and the effect of palliative care on patients with hepatocellular carcinoma 1,8–10 …”