Authors: Dr. Ayaskant Pany, Sorika Van Niekerk, Johan Venter, Nuria Martinez-Alier, Viola-Marie Raubenheimer
Increased global travel means that infectious disease outbreaks are spreading faster and further than ever before. Recent outbreaks of Ebola, Cholera, Measles, Lassa Fever and other diseases across Africa and other low and middle income countries (LMIC), create a significant medical, economic, and social burden, that requires collaboration between public and private organizations to resolve.
The pharma industry, as well as many not for profit, governmental, non-governmental and philanthropic organizations, are working hard to address these outbreaks through the development of treatments and vaccines. However, infectious disease trials face many obstacles that make this research especially difficult. Many of these challenges are related to the geography. Frequently, infectious disease trials are conducted in remote communities in LMIC, which is appropriate as this is where these diseases are often prevalent. However, the lack of mature trial sites and labs, limited research experience/expertise in the talent pool, and inconsistent access to basic infrastructure can make the operational aspects of clinical trials challenging from the outset.
A critical component of every infectious disease trial are the laboratory tests, which in many instances are used to meet primary/ secondary endpoints and trial objectives. Many of the trial sites lack access to controlled laboratory testing technology, trained lab technicians, reliable reagent supply, and power to support lab operations. In the absence of laboratories within region or country, it is required to send samples to other countries or facilities. However, due to the challenges faced, even simple tasks like shipping lab samples can become very difficult in certain places in Africa, where roads and adequate transport are unreliable. Yet, this activity is vital to the success of these research efforts.
Sponsors must also consider the quality and consistency of data being produced from often isolated and distant trial sites. When a trial involves multiple sites stretched across remote communities, chances are high that data capture and storage methods will vary considerably, making it challenging to review results, and conduct site monitoring.
Despite these challenges, infectious disease trials can be delivered successfully, assuming sponsors find the right partners, and set aside enough time to plan, launch and oversee these operations.
When planning an infectious disease trial, some obstacles that sponsors may face include:
- Finding key opinion leaders (KOLs). Because there are fewer KOLs with clinical trial experience in these communities, it is useful to identify them first – then select sites in their proximity, or with their guidance. This tailored KOL and investigator identification and involvement allows for community engagement, faster regulatory approvals, rapid trial set-up and effective trial execution.
- Site selection/construction. In many cases, these communities will not have experienced trial sites or labs where research can be reliably conducted that meets global regulatory standards. In these instances, the best approach may be building a trial site and lab from the ground up. We’ve seen great success building up labs and sites in connection with local academic institutions to close these gaps in clinical trial maturity.
For example, a malaria vaccine trial for a large pharmaceutical company was run at 11 centers in seven countries in sub-Saharan Africa, many of which were academic sites. To support the work, the sponsor upgraded infrastructure, built new labs, and upgraded laboratory equipment, including chemistry analyzers and blood culture machines.
- Staff training. Even when clinical research sites exist, additional training may be required to ensure the trial operations meet global regulatory standards and Good Clinical Practice (GCP) requirements for conducting trials. For example, in the malaria trial mentioned above, IQVIA provided extensive training on GCP, study conduct, study processes, and adhering to the protocol as well as the sites own Standard Operating Procedures (SOPs). Sites were also asked to provide a set of SOPs in order to run the study, which were reviewed by IQVIA prior to study start.
Training for infectious disease trials in these communities may also include guidance on appropriate methods for recruiting, screening candidates, obtaining patient consent, capturing data in a technology-based environment, performing study procedures and patient retention.
Ideally, sponsors / CROs will perform a pre-assessment of trial sites to identify any knowledge or skill gaps that need to be addressed so training can be completed before the first patient is recruited. This is important because, unlike other indications, infectious diseases and vaccine trials often experience a surge of patients eager to participate. If site staff are not adequately trained to address the trial and subject needs on day one it can lead to reduced recruitment, lower rates of retention, poor protocol adherence and low data integrity.
- Community engagement. These trials cannot be operated remotely. Sponsors and their CROs need team members on the ground working directly with site staff, subjects and engaging with investigators and community leaders. This will ensure the trials are conducted according to standards, and that the community welcomes and supports the project.
Investing in training, infrastructure and healthcare can be a tremendous value to a community but only if its members feel engaged in the process and understand the benefits. If sponsors fail to work with community leaders, or appear to be capitalizing on the vulnerability of subjects rather than helping them address a real medical concern, these trials can generate negative public attention that can damage the project and the brand.
When our teams work on trials in these communities, the first step we take is to meet with community advisory boards to communicate our goals, gather their feedback on the best ways to proceed, and secure their buy-in for the research. These early engagements have been key to advancing safe and successful trials, and to building sustainable talent and infrastructure that benefits the entire community and ensures support for trials in the future.
- Regulatory infrastructure. In certain countries, the regulatory infrastructure is in its infant stages and are evolving on a regular basis. It is critical to keep updated with the latest structures, requirements, and SOPs to ensure regulatory applications are prepared and submitted as per the most up to date information. Communication with the regulators are highly reliant on the KOL or Primary Investigators at sites to execute key processes and is critical to build close relationships with the key players and share lessons learned internally and externally.
- Logistic and laboratory infrastructure. As indicated above, the laboratory samples in many instances have a direct impact on the primary outcome of the trial. It is critical that the partner selected has appropriate knowledge, experience and selects the appropriate vendors to accommodate the specific nuances of the trial. Due to potential high sample volumes, the systems used from a laboratory point of view for sample receipt, tracking, storage and onward shipment should be robust to ensure chain of custody throughout the process. We, at Q2 Solutions, have developed extensive experience in managing laboratories as well as other clinical trial lab related dynamics specific to infectious diseases. With experience, we have gained an understanding as to what laboratory delivery model is appropriate for the specific trial type. In certain instances, there is a need for a hybrid strategy, where one combines local laboratories within country with a central laboratory, to accomplish the objectives of the trial. From a logistical point of view, we have evaluated and partnered with the correct vendors specific to a country since there is not a “one-size that fits all”. We are open to sharing our experiences for the optimal delivery of these studies.
All these steps require added time and resources to the project plan, but they are vital if sponsors want to conduct effective infectious disease trials that meet regulatory and ethical guidelines for clinical research. Working with a global partner that has local experts with the knowledge and networks in place to operate trials in these remote communities can expedite start-up while ensuring all quality, safety and efficiency goals are met.