3. With a large pool of treatment-naive patients, Vietnam is an attractive location for conducting vaccine trials.
Our experience of conducting vaccine or other preventive medicine trials in Vietnam has given us insights into a site model. We call it the “Leading Site Model” in which one site leads by supporting overall execution of a study, including but not limited to site recommendation, enrolment etc.
The primary objective of this study was to assess the exemplary attributes of the Leading Site Model in Vietnam and its subject accrual potential compared to other SEA countries.
Materials and Methods
For the purpose of analysis, the following data sources and assumptions have been used:
Selection of trials
All vaccine trials conducted by Quintiles included at least one Asia-Pacific country and enrolled healthy subjects. Data were downloaded from Quintiles Performance Metrics database in November 2013. The downloaded data were further screened to include trials that included Vietnam as one of the countries, along with other SEA countries.
From the selected trial, information about the Health-care system in Vietnam and its role in the Leading Site Model, criteria for selecting Leading Site and other advantages of the Leading Site Model were collected for qualitative analysis of the efficiency of the Leading Site Model.
Quantitative parameters such as total number of sites, total subjects enrolled and subjects enrolled per site were also analyzed for efficiency of the Leading Site Model in Vietnam.
We also acknowledge the potential limitations of this analysis based solely on one healthy vaccine trial conducted by Quintiles and the findings cannot be generalized to the broader aspects of trial conduct in Vietnam.
Results and Discussion
Of the 50 vaccine trials that included at least one country in Asia-Pacific, 38 trials enrolled healthy volunteers. Only two of the 38 included Vietnam and at least one other SEA country, of which only one (Trial 1) had complete data for analysis. In addition to Vietnam, four other SEA countries were involved in Trial 1, herein referred to as countries A, B, C, and D. The number of vaccine trials registered in Clinicaltrials.gov in each of these countries from 2004 to 2013 is illustrated in Table 1. Country C and D are ‘veterans’ in conducting vaccine trials; Country B is more experienced than Vietnam, and Country A is the least experienced among the five countries.
The results showed that Country C enrolled the highest number of subjects, contributing 34% of more than 10,000 subjects enrolled in Trial 1. Vietnam, which is next in line, contributed 23%. Country A, B and D contributed 18%, 14% and 11% respectively. Country A included the maximum number of sites, hence the number of subjects enrolled per site was the lowest. The subjects enrolled per site were highest in Country C, followed by Vietnam.
The Leading Site Model in Vietnam is unique and its emergence can be attributed to the country’s healthcare system. The healthcare system in Vietnam is organized into four administrative levels (central, provincial, district and commune) as illustrated in Figure 2. The central level is managed by the Ministry of Health (MOH) and health sections of the people’s committee at provincial and district levels.
MOH comprises departments with various responsibilities, two of which are curative and preventive systems. The General Department of Preventive Medicine is responsible for preventive care in Vietnam4. The curative system includes all curative care including examination and treatment, whereas the preventive system includes the control of communicable and non-communicable disease; human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS); prevention of injuries; school health; occupational health; community nutrition; safe water; vaccines and biomedical products; chemical and pesticide control; food safety; health promotion; and production of vaccines and biomedical products.
Under the preventive medicine system, central research institutes such as Pasteur Institute, National Institute of Nutrition (NIN), National Institute of Hygiene and Epidemiology (NIHE), National Institute of Malariology, Parasitology and Entomology (NIMPE) are established at a national level and are subordinated to the MOH. These central research institutions provide technical guidance for national and regional preventive health activities. Hence, preventive medicine trials in Vietnam always include one of the central research institutes as a leading site for successful delivery.
The Leading Site Model emphasizes the importance of choosing the right leading site for successful conduct of preventive medicine trials. The parameter for choosing leading sites within available central research institutes varies based on the indication, category of investigational product and access to patient pool in terms of prevalence/incidence. The Pasteur Institute in Ho Chi Minh City (Southern Vietnam) was selected as a leading site for Trial 1 as there is a higher transmission rate for the disease that the vaccine is indicated for in the south of Vietnam as compared to the north. It has excellent collaboration with the provincial and district level Preventive Medicines Centers (PMC) in the south. Even though the study required healthy subjects, it makes sense to study the effects of a vaccine in an area where the disease is prevalent. Vietnam stands second in terms of subject enrolment in Trial 1 indicating the effective management by a leading site in enrolling subjects for a trial. No other country in Trial 1 reported the involvement of one leading site supporting overall subject enrolment and management of trial.
In Vietnam, the subjects can be enrolled at the provincial, district or even communal level for a preventive medicine trial depending on the target indication.
Our analysis revealed the following primary advantages of including a central research institute as a leading site in this trial:
- Providing assistance in selecting the best sites at subsequent levels (provincial, district and commune) based on its relationship & up-to-date knowledge on epidemiology of various diseases;
- Providing guidance on protocol design as the leading sites are involved in providing technical guidance at a national level;
- Providing oversight to the provincial and district level PMC;
- Providing resources e.g. site staff to support subject enrolment at subsequent levels and facilities required to store/transfer investigational product (IP), source documents and samples etc; Other exploratory findings of the Leading Site Model in Vietnam are:
- Having one Ethics Committee (EC) submission (to the leading site EC) is satisfactory;
- The leading site also provides support in submission and to address questions from MOH EC thereby expediting the approval process;
- The leading site can add more PMCs in order to meet the recruitment requirement (if necessary) post MOH approval. There is no need for additional approval from MOH to add more PMCs at district or communal level;
- The leading site assists in obtaining Site Information Forms (SIFs) and Confidentiality Agreements (CDAs) from provincial and district level sites due to their established relationship with sites;
- The leading site provides excellent support for trials at sub-urban areas or at the commune level where recruitment potential may be higher for some indications;
- Maintaining treatment adherence, patient diary completion etc can be closely managed and monitored through Village Health Workers usually working at the household-level in communities;
Further, the quantitative parameters from the selected trial were used to analyze the efficiency of the Leading Site Model using the 2x2 matrix model (Figure 3). One dimension of the matrix comprised of the total number of sites per country and the other dimension looks at the site potential in terms of subjects enrolled per site. The two dimensions are plotted as bubbles on a 2x2 matrix. The position of the bubble in a matrix corresponds to the intersection of two aspects. The most desirable zone being the upper right zone marked in green followed by the yellow zone in the centre and red being the least desirable. A country in the green zone has higher subject accrual potential. The area occupied by a bubble represents the total subjects enrolled in that country. A bubble occupying a larger area will mean the country has overall enrolled more subjects. However, it is important to note here that the bubble area is not directly related to the other two dimensions. Overall a country may have enrolled more subjects but the number of subjects enrolled per site could be lower if there were sites included in the country. For example Country A enrolled 1,870 subjects in total but the number of subjects enrolled per site is the lowest in the trial as it involved 11 sites whereas Country D enrolled only 1,170 subjects in total but the number of subjects enrolled per site is higher than Country A.
Country C and Vietnam are in the most desirable zone clearly indicating their efficiency over the other three countries in enrolling subjects in this healthy vaccine trial.
There are, however a few challenges with the Leading Site Model; these challenges can be addressed by establishing some consensus on the approach with the Principal Investigator (PI) at the beginning of the study:
- Delegation of tasks by the Principal Investigator (PI) to the Sub-investigators or the study coordinators, and
- Communication channel between the PMCs and the EC to ensure adequate oversight.
Our analysis reports that Vietnam is an optimal country for conducting preventive medicine trials. Country C being a veteran country in conducting vaccine trials in Asia-Pacific typically faces intense competition for the conduct of vaccine trials. Vietnam stands out as a possible alternative to Country C with similar subject accrual potential. The Leading Site Model for conducting preventive medicine trials in Vietnam is well-established and Quintiles has been successfully conducting preventive medicine trials following this model. Whilst the findings of the study holds good in terms of subject accrual potential of the Leading Site Model, there is, a limitation that the findings are based on data from just one vaccine study.
About the Author
Assoc. Patient & Site Services Manager, Integrated Site Services Regional SID, Asia
Saumya has over seven years of experience in clinical research, of which she has spent four years focusing specifically on feasibility studies in Asia-Pacific region for various indications. Saumya’s work at Quintiles involves leading and directing stand-alone feasibility and site-identification projects in Asia-Pacific to ensure recommending best strategy during the initial planning of a clinical trial with regards to sites and investigators.
Before joining Quintiles, Saumya was also a biotechnology lecturer at one of the affiliated colleges of Bangalore University, in Bangalore, India. She holds a masters degree in Biotechnology and a bachelor of science in chemistry, botany & zoology from the Karnatak University Dharwad (KUD).
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