For over 10 years, Rho has worked in vaccine research and is currently 1 of 5 contract research organizations in the BARDA Medical Countermeasures Clinical Studies Network (MCM-CSN) that designs and conducts clinical studies needed to develop drugs, vaccines, and diagnostic tests that help protect public health. Based on our experience, we understand the risks, challenges, and solutions needed to operationalize a vaccine trial.
One of the biggest considerations for your vaccine program is early planning. The planning conducted during start-up will have the biggest impact on the successful execution of the trial. While this is true for all studies, certain vaccine trials can enroll very quickly, leaving little room for error once enrollment starts; for example, Rho worked on a recent MCM-CSN pandemic influenza vaccine study that enrolled over 360 patients in 3 days at 4 clinical sites. Advanced planning is needed to ensure the sites are trained and ready, because any misunderstanding of the protocol has the potential to affect every subject enrolled. Our teams have mitigated this risk through detailed protocol training and expectation setting during site initiation visits and by having a clinical monitor on-site for the first day of enrollment. The monitor can answer questions and review site documentation to ensure that the study is being conducted and documented, as expected.
Additionally, having data management, data standards, and statistics involved early in the process will support the data cleaning and issue and trend detection that is needed. To ensure the safety of participants in the study, detecting events that meet stopping rules as quickly as they occur is needed. Rho typically sets-up automatic alerts when events that can lead to a stopping rule occur, so the study team is prepared for a rapid response. By working to have datasets programmed prior to first patient in, all safety monitoring tools can be ready once the study starts enrolling and any ad hoc Safety Monitoring Committee (SMC) meetings can be held quickly. On a recent MCM-CSN Anthrax vaccine trial, a stopping rule for SMC review occurred while enrollment was still ongoing and participants still had to receive subsequent vaccinations. With these measures in place prior to enrollment starting, we detected the potential safety concern and held a SMC meeting to review the cases within 3 days of the event occurring. This allowed us to continue with enrollment and subsequent rounds of vaccinations on-schedule after SMC approval to move forward. Having an integrated approach to risk assessment, prevention, and mitigation strategies during protocol development and study start-up made for quick identification, escalation, and mitigation of the issues as they arose.
However, not all vaccine studies enroll quickly. While the same approach to risk-based quality management is needed during protocol development and study start-up, if enrollment will be a challenge, additional considerations about patient education need to be reviewed during this time. Slower enrollment in vaccine trials can occur because of misperceptions about vaccines. Potential participants could be concerned that the vaccine would cause them to get the illness or that the trial will expose them to the disease. Working with the site to provide additional education about the vaccine, the risks, and the benefits of the trial is needed to support recruitment and retention.
Another concern of potential participants is what happens if the vaccine causes them harm. Informed consent documents will detail study specific information, and sites should be prepared and trained to answer the questions participants might have. Certain vaccines will need additional language in the informed consent based on the Public Readiness and Emergency Preparedness Act (PREP Act). In October 2010, the PREP Act went into effect and established the Countermeasures Injury Compensation Program (CICP) that is designed to provide benefits to individuals who sustain some types of serious physical injuries as a direct result of use of certain countermeasures that are detailed on the Health Resources and Services Administration’s website. If the vaccine being studied is covered under the PREP Act, additional language discussing CICP should be added to the informed consent and an additional information sheet about CICP, including how to file a claim, should be provided to each participant.
Early preparation and a robust risk based quality management process is essential for any trial’s success. For vaccine studies, given the high potential for fast enrollment and frequent safety reviews, having the study team work together during protocol development and study start-up to identify risks and provide prevention and mitigation strategies for them is needed for the trial to be conducted successfully. Having a partner who understands the risks and the best strategies to mitigate or prevent them can set you on the right path.
If you need help conducting your vaccine trial, our experts can support your protocol development and study conduct, providing guidance on operational considerations and risk mitigation strategies.
Gloria David, PhD, MHSc, Principal Research Scientist, holds a PhD in Pharmacology and Molecular Sciences from Johns Hopkins University School of Medicine, a Master of Health Sciences in Clinical Research from Duke University School of Medicine, and a BS in Biochemistry from the Pennsylvania State University. Dr. David serves as Rho PI for the Medical Countermeasures Clinical Studies Network (MCM-CSN) contract funded by the Office of the Assistant Secretary for Preparedness and Response (ASPR), Biomedical and Advanced Research Development Authority (BARDA). Under this contract, Rho provides clinical services to facilitate medical countermeasures product development toward licensure. Trials evaluate chemical, biological, radiological, nuclear, pandemic influenza, and emerging infectious diseases countermeasures. Dr. David has provided scientific and technical leadership for 6 vaccine studies funded by the NIAID. She served as PI on 2 studies in patients with atopic dermatitis examining the safety and immunogenicity of an intradermal influenza vaccine. She also served as co-PI on a study assessing the safety and immunogenicity of the 2009 H1N1 vaccine in adults and children with severe asthma. She has provided leadership for a yellow fever vaccine study and a varicella vaccine study in patients with atopic dermatitis and for a keyhole limpet hemocyanin adjuvant study. Dr. David currently serves as PI for 2 vaccine studies funded by BARDA: a Phase 2 study to investigate the efficacy of H7 influenza vaccine with adjuvants as a safeguard to the public against pandemic influenza and a study to investigate the safety and immunogenicity of anthrax vaccine in individuals over 65.
Since joining Rho in 2004, Dr. David has served as co-PI of the Statistical and Clinical Coordinating Center (SACCC) for the National Institute of Allergy and Infectious Diseases (NIAID)-funded Inner-City Asthma Consortium (ICAC; 2004-2015) and as PI of the NIAID-funded Atopic Dermatitis Vaccinia Network (ADVN; 2008-2011) and the Atopic Dermatitis Research Network (ADRN; 2010-2015) Coordinating Centers. Dr. David also currently serves as a Lead Scientist for the Asthma and Allergic Diseases Group for the NIAID Division of Allergy, Immunology, and Transplantation: Statistical and Clinical Coordinating Center (2015-2022). She is responsible for the scientific and technical oversight of the performance of the coordinating center’s work, including clinical operations, data management, and statistical, technical, regulatory, and administrative support. She works directly with the NIAID Project Office and clinical investigators to define project needs and is responsible for building cross-functional teams at Rho to meet those needs and for coordinating all activities to ensure the successful completion of all projects. She also provides oversight for subcontractor activities (e.g., drug distribution, safety labs, sample analysis, and repository sample storage).