To many industry veterans, clinical development in China carries negative connotation. Among other things, quality has and continues to be a concern. Since 2015, things have dramatically changed for the better. But on the ground, how is the situation? If you are eyeing for a clinical trial that includes China, you need to have the confidence in the system. We decided that one way to assess the situation is to talk to the clinical researchers on the front line.
FMD recently interviewed Dr. Huang Huiyao of the Cancer Hospital of China Academy of Medical Sciences (CHCAMS), one of the top academic hospitals in the country. Dr. Huang is the Academic Secretary of the Clinical Trials Center of CHCAMS. In 2018, CHCAMS was the leading site for 184 cancer trials – which accounted for 12% of ALL cancer trials conducted in the country last year. Many of these trials are from global drug companies. Her perspective can give you some insights on what is happening on the ground. Please note the content of this article represents personal views of Dr. Huang. It does not represent the positions of CHCAMS or FMD.
FMD: Can you describe CHCAMS?
Huang: CHCAMS is the first cancer specialty hospital in China. It was founded in 1958 as the first cancer-focused hospital in China. CHCAMS initiated China’s first cancer trial in 1960. The hospital has been modernizing continuously. In 1996, the hospital established the first cancer specific Ethic Committee, subsequently in 1997, it was approved as the first batch of clinical research centers for anticancer drugs.
FMD: Can you put CHCAMS’ research in perspective?
Huang: Using the last full year results, CHCAMS participated in 246 investigational cancer trials, which represents over 1/3 of all such trials in China. Out of the 246 trials, CHCAMS was the lead investigational site for 184 trials. We work with many global companies in these trials. From 1996 to 2018, CACAMS led or participated in registrational trials for over 110 anticancer drugs from 65 global companies that received marketing authorization in China. CHCAMS participated in or led pivotal trials for 14 of 15 cancer drugs approved in China in 2018.
FMD: That is fantastic.
Huang: It is One key reason we can carry out quality trials is the well trained and experienced clinical research personnel. We are now conducting 73 Phase I cancer trials. These trials are managed by several dozen Principal Investigators well experienced in early stage clinical research.
FMD: With that volume of investigatory trials, do you have enough patients?
Huang: CHCAMS is in good position to attract patients from all over China. The hospital provides services to over 1 million outpatients and 80,000 cancer inpatients annually. Patients come from all over China to CHCAMS as they believe that we have the best expertise to treat patients with cancer. The patients are highly motivated to participate in clinical trials as there are not many effective treatments available in the
market. The hospital has an efficient process to identify qualified patients and a transparent platform to keep them informed about the trials.
FMD: If I were an international drug company, one of the first questions to you would be how you ensure trial quality?
Huang: At the GCP center we have multiple layers of monitoring and checks to ensure the operations are done in a compliant fashion. Before we open for enrollment, it is mandatory to conduct three meetings: investigators, dry-run, and kick-off. Each staff member involved in a study will have thoroughly learned the protocol, the conduct of the trial in addition to potential safety issues and counter measures. Through these preparations we can identify the adequate staffing level, including CRO and SMO supports. During the trial, CHCAMS routinely conducts risk-based audits to detect problems early on and implement correction plans if warranted. At the trial close-out phase, CHCAMS has its own closing quality-control procedures in addition to the CRO’s. More importantly, we emphasize training, especially for those first-line practitioners. Through these measures, we can ensure compliance, accuracy, and completeness for every trial. CHCAMS receives more than 20 inspections by the NMPA annually without any major findings.
FMD: Time is of essence in clinical development, especially in the project start-up phase. FMD has faced some challenging situations. What are your thoughts on this?
Huang: We fully appreciate the concerns of startup time by drug developers. It is to the benefit of everyone: the company, the hospital, the CRO, and most importantly, the patients, to have a quick and smooth startup. At CHCAMS, we have streamlined the process that leads to efficient site initiation and patient recruitment. For instance, we allow parallel EC review while the NMPA reviews the IND application. We also start contract negotiation during this time. These can shorten the startup time by 2-4 months.
FMD: What about patient enrollment? That has been an overarching challenge to all companies.
Huang: I know that across America and Europe, cancer trial enrollment is and will continue to be a major issue. The typical trial is about 0.2 enrollee/site/month. This has become the major roadblock for innovative drug research. However, in China the average trial enrolls about 2.6 patients per site per month.
FMD: How did you achieve higher enrollment rates?
Huang: China has the largest patient pool in the world. These patients and their families have high willingness to participate in clinical trials, especially cancer trials.
FMD: Another interesting development in China is the regional networks. FMD was fortunate to play a role in the Beijing Oncology Clinical Research Association. As a founding member, can you give an overview of this this collaborative effort?
Huang: This is a positive development with long lasting impact. Beijing has probably the best resources for cancer care in China. This association further integrates these dispersed resources to better serve patients and innovative drug development. For example, the association is pushing for more standardized EC process across Beijing City. We are coordinating expert panels to revise guidance documents for diagnosis, treatment, and trial conduct. One of our goals is to strengthen connections with international drug companies to accelerate global development.
FMD: What is your advice to global drug companies?
Huang: Just like any other country, China has many specificities in the drug development arena. For instance, Human Genetic Materials Office will have to approve every trial. This is unique to China.
The company is best served to collaborate with a reputable CRO with deep China knowledge and experience. The CRO will help the company to prepare all required regulatory documents, select proper sites, manage trial operations, and eventually the NDA submission and communication with the NMPA. The company needs to keep an open mind to fulfil those regulatory requirements even though they may not be required in the US or Europe.
PLAN AHEAD and be realistic. Even though the NMPA has shorten and streamlined many processes, preparation of a clinical trial is a lengthy task in any country.
Find those who you want to work with, be it clinical site or CRO. Can you communicate with them efficiently? Are they responsive? Do they have the experience important to you? And face to face meeting is still the best way to engage people in the age of Skype.
Last but not least, use a SMO. They fulfill the roles of trial coordinators. Few sites have their own internal clinical research coordinators – another local flavor in China. They are important in recruiting, scheduling, training, data collection, and patient engagement. They are a critical component of a trial.
Huiyao Huang, PhD, Epidemiology and Health Statistics
Academic Director of Clinical Trials Center of National Cancer Center, Cancer Hospital Chinese Academy of Medical Science. Member, Bio similar Collaborate Team in China. Member, Clinical Research Committee of Beijing Oncology Society. Editor, CA Chinese edition editorial department.
As the Academic Director, Dr. Huang has been dedicated to clinical epidemiological research, pharmacoeconomic evaluation, statistical design and analysis. She has published more than 20 academic papers, with more than 10 published in Chinese core or SCI journal papers as the first author.