TSUNG-HAO LIUYU-YUN SHAOLI-CHUN LUYing-Chun ShenCHIUN HSUZHONG-ZHE LINCHIH-HUNG HSUANN-LII CHENG2020-04-092020-04-092019-07-0317474124https://scholars.lib.ntu.edu.tw/handle/123456789/484020© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Introduction: Clinical trials in hepatocellular carcinoma (HCC) exhibit a high degree of heterogeneity. These heterogeneities may lead to unexpected results among clinical trials. Area covered: In this review, we address the heterogeneity noted in early phase HCC trials, trials involving transarterial chemoembolization, and advanced HCC trials. Furthermore, we discuss possible methods to attenuate the detrimental effects of heterogeneity when conducting clinical trials. Expert opinion: Clinical trials in HCC exhibit an inherently high degree of heterogeneity because of various reasons: tumor heterogeneity, different cirrhotic backgrounds, various etiologies of cirrhosis, and geographical differences in practice and expertise. Such heterogeneity may cause imbalance among the enrolled patient population, premature withdrawal from the clinical trial, and variable response to the treatment. In addition, methodological heterogeneity also exists in designing trial protocol and response evaluation. All these factors may eventually lead to conflicting results among clinical trials. Accounting for these heterogeneities is important to foster the success of future trials. In recent years, significant progress with molecular targeted agents and immune checkpoint inhibitors was made in advanced HCC. These new agents are also being tested in clinical trials involving earlier stage HCC and will also face the challenge of these issues.Clinical trial | hepatocellular carcinoma | heterogeneity | trial designClinical trial; hepatocellular carcinoma; heterogeneity; trial design[SDGs]SDG3alpha fetoprotein; atezolizumab; bevacizumab; brivanib; cabozantinib; interferon; iodinated poppyseed oil; ipilimumab; lenvatinib; nivolumab; orantinib; pembrolizumab; placebo; ramucirumab; regorafenib; sorafenib; antineoplastic agent; adjuvant therapy; cancer prognosis; cancer staging; cell heterogeneity; chemoembolization; Child Pugh score; clinical practice; clinical trial (topic); geography; human; liver cell carcinoma; liver cirrhosis; liver resection; medical decision making; methodology; outcome assessment; overall survival; patient selection; progression free survival; recurrence free survival; recurrence risk; research subject; Review; treatment response; treatment withdrawal; unspecified side effect; chemoembolization; clinical trial (topic); immunotherapy; liver cell carcinoma; liver tumor; methodology; molecularly targeted therapy; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Clinical Trials as Topic; Humans; Immunotherapy; Liver Neoplasms; Molecular Targeted Therapy; Research Designother10.1080/17474124.2019.1621165311328872-s2.0-85067630950https://api.elsevier.com/content/abstract/scopus_id/85067630950