Conducting randomised controlled trials across countries with disparate levels of socio-economic development: The experience of the Asia-Pacific Hepatocellular Carcinoma Trials Group

Abstract

Hepatocellular carcinoma (HCC), which constitutes over 85–90% of all primary liver cancers, is the most predominant type of liver cancer, and the third leading cause of cancer related deaths in the world. While the Asia-Pacific is a highly heterogeneous region in geography, ethnicity and in the level of socio-economic development, the main burden of HCC falls in this region and there are compelling reasons and advantages to conduct definitive clinical trials in HCC where it is endemic. The Asia-Pacific Hepatocellular Carcinoma (AHCC) Trials Group was established in 1997 and has faced and overcome challenges that are inherent in conducting clinical trials in a disparate region. Clinical trial infrastructure is rudimentary at many sites and requires significant effort to be expended on training and monitoring to ensure production of definitive data. The benefits of industrial support of Investigator-Initiated Trials are discussed in the context of the Asia-Pacific. The positive experience of the AHCC trials group would be valuable to any collaborative trials in countries with disparate levels of socio-economic development.

Introduction

Hepatocellular carcinoma (HCC), which constitutes over 85–90% of all primary liver cancers, is the most predominant type of liver cancer, and the third leading cause of cancer related deaths in the world [1]. It has been estimated that HCC results in 650,000 deaths yearly, of which two-thirds are from Asia [2].

While HCC itself has been reported to be associated with many risk factors including dietary aflatoxin exposure [3], alcohol consumption [4], obesity [5] and diabetes [6], chronic viral hepatitis is most important risk factor [7]. The geographical prevalence of HCC in this region is attributed to the high incidences of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, the main etiological agents for HCC [8], [9], [10], [11]. HBV and HCV account for 80–90% of all HCC worldwide [12].

The resources and expertise required to conduct randomised controlled trials (RCT) were previously confined to economically more developed nations, mainly outside of the Asia-Pacific. There was a consequential paucity of randomised controlled trials in HCC in the endemic regions of the Asia-Pacific and other developing nations.

Clinicians in Asia however share a common goal of seeking efficacious treatment for a cancer epidemic in the region that had few available therapeutic options. This impetus marked the beginning of the AHCC trials group. Subsequently other groups in the region similarly embarked on multi-centre cancer trials namely the Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers (ASCOLT) trial [13] and the Nimotuzumab and Cisplatin/Radiotherapy for locally Advanced Head and Neck Squamous Cell Cancer trial [14].