Clinical Trials and U.S. Military Veterans

The participation of U.S. military veterans in clinical trials dates back to the early 20th century but became more formally integrated into medical research efforts following World War II. One of the earliest and most influential developments occurred in 1925 when Congress established the Veterans Bureau, the precursor to the U.S. Department of Veterans Affairs (VA), acknowledging the need for structured medical care for returning soldiers. By 1946, the creation of the Veterans Health Administration's medical research division set a foundation for organized, large-scale clinical investigations involving veterans.

Significant advancements from these trials include the development of key psychiatric treatments for post-traumatic stress disorder (PTSD) and traumatic brain injuries (TBI), both prevalent among returning Vietnam and Gulf War veterans. Historical data show that nearly 70% of VA-sponsored research between 1970 and 1995 focused on psychiatric and neurological conditions, largely due to the mental health impacts of military service.

During the HIV/AIDS crisis in the 1980s, veterans played a crucial role in trials for antiretroviral medications. Recent decades have seen veteran involvement drive innovation in prosthetic technologies, cancer therapies, and treatments for chronic diseases like diabetes and cardiovascular illness.

Importance of Veterans in Medical Research

Veterans are a uniquely valuable population for clinical research due to their distinct exposures, health risks, and demographic profiles. Many have experienced intense physical and psychological stressors during service, making them key participants in studies related to trauma recovery, rehabilitation, and both chronic and service-related illnesses.

Key reasons veteran participation is crucial include:

• High prevalence of chronic conditions: Veterans face elevated rates of musculoskeletal disorders (56%), PTSD (11–20% depending on era served), and diabetes (25% higher than the civilian population).
• Diverse backgrounds: Racial, ethnic, and gender diversity among veterans allows for more representative trials.
• Access to integrated health data: The VA’s electronic health record system offers a robust and secure platform for longitudinal research, reducing data gaps.

Clinical research involving veterans not only improves care delivery within the VA but also contributes broadly to U.S. public health knowledge.

Types of Clinical Trials Conducted with Veteran Participation

Veterans participate in various categories of clinical trials, each designed to evaluate different aspects of medical care or treatment efficacy. The Veterans Health Administration and its affiliates, including the Veterans Research Foundation of Pittsburgh, facilitate a wide array of trial designs.

Intervention-Based Trials

These studies evaluate the effectiveness of new drugs, surgical procedures, or behavioral therapies. For instance, the VA Cooperative Studies Program has conducted over 100 multisite clinical trials including large-scale trials of blood pressure medications and prostate cancer screening.

Observational and Cohort Studies

These exams track health outcomes over time without altering treatment. The Million Veteran Program (MVP), launched in 2011, is among the world's largest genomic databases with over 950,000 participating veterans. It aims to understand the roles of genes, lifestyle, and exposures in illnesses.

Device and Prosthetics Trials

The VA is a global leader in assistive technology trials. Veterans were instrumental in developing advanced prosthetics such as the LUKE Arm, which provides near-natural arm movement using mind-controlled technology.

Mental Health and Behavioral Research

Given the mental health challenges veterans face, trials on PTSD treatments, suicide prevention, and substance use disorder are especially prominent. One example is the CSP #591 study, evaluating prolonged exposure therapy for veterans with PTSD.

Health Outcomes and Benefits for Veterans through Clinical Trials

Clinical trial participation often translates directly into improved health outcomes for veterans. Research integrated within the VA system tends to focus on high-impact conditions that disproportionately affect veterans.

Improvements in Condition-Specific Treatment

• PTSD: Behavioral therapies studied through trials like PE (Prolonged Exposure) and CPT (Cognitive Processing Therapy) have been mainstreamed into VA mental health services.
• Diabetes Management: The ACCORD and VADT trials, with significant veteran participation, led to updates in diabetes treatment guidelines.
• Cardiovascular Health: Trials like COURAGE showed that medication and lifestyle changes could be equally effective as surgery for chronic heart conditions.

Early Access to Advanced Care

Veterans involved in trials often receive cutting-edge treatments earlier than the general population. For example, veterans with cancer can access immunotherapy agents during experimental phases not yet available in standard settings.

Enhanced Personal and Community Health

Clinical research empowers veterans to take an active role in managing their health. Moreover, their participation improves the broader veteran community’s outcomes through more accurate diagnosis, prevention, and treatment models.

Ethical Considerations and Protections for Veteran Participants

All clinical trials involving veterans must adhere to strict ethical guidelines regulated by federal law. The VA has one of the most comprehensive oversight systems to protect participants.

Institutional Review Boards (IRBs)

Before any trial begins, it must be approved by a federally registered IRB, including at least one member not affiliated with the research entity. The IRBs assess risk-benefit ratios, informed consent processes, and data protection protocols.

Informed Consent Requirements

Veterans must be fully informed about the objectives, risks, benefits, and alternatives before participating. Consent is documented and continually reaffirmed during the trial process.

Oversight Agencies

The Office of Research and Development (ORD) within the VA and federal bodies such as the FDA and OHRP (Office for Human Research Protections) provide centralized monitoring. The VA also maintains a Research Compliance Officer in each medical center.

Protection of Vulnerable Populations

Special care is taken when including veterans who may be in dependent positions, such as those undergoing rehabilitation or inpatient care, to eliminate coercion and ensure voluntary participation.

Role of the Veterans Research Foundation Pittsburgh in Clinical Trials

The Veterans Research Foundation Pittsburgh (VRFP) is a key driver of research excellence at the VA Pittsburgh Healthcare System (VAPHS). Founded in 1989, VRFP fosters collaboration, supports scientific faculty, and enables groundbreaking studies across diverse medical fields.

Facilitating Research Infrastructure

VRFP manages millions in grant funding annually to administer research resources, staff support, and regulatory compliance. It plays a crucial role in integrating academic partners such as the University of Pittsburgh and Carnegie Mellon University.

Notable Clinical Trial Support

• Neuroscience: VRFP supports trials examining novel treatments for traumatic brain injuries and spinal cord injuries.
• Geriatrics and Aging: It backs studies on Alzheimer’s disease and related dementias, for which veterans are at increased risk.
• Precision Medicine: VRFP collaborates with the MVP initiative to support local and national genetic studies.

By connecting funders, scientists, and clinical practitioners, VRFP ensures Pittsburgh remains a national leader in veteran-inclusive medical research.

Challenges and Barriers Faced by Veterans in Clinical Trial Participation

Despite clear medical benefits, many veterans face barriers that prevent or limit their involvement in clinical research.

Logistical Barriers

• Transportation issues: Especially relevant for rural veterans who reside far from VA medical centers
• Time commitments: Trials often require repeated visits that interfere with employment or family obligations

Mistrust and Historical Concerns

Past unethical research practices, such as the controversial Edgewood Arsenal experiments during the 1950s and ’70s, have fostered lingering distrust. Efforts to rebuild trust include transparency, ethical oversight, and veteran-led recruitment strategies.

Comorbid Conditions

Many veterans have multiple chronic illnesses or take medications that exclude them from trial eligibility due to conflict with study protocols.

Digital Literacy and Access

Online enrollment systems pose barriers for older veterans or those without regular internet access, despite the VA offering some digital navigation support.

Future Directions for Clinical Research Involving Veterans

The future of veteran-involved clinical research is shaped by innovation, policy reforms, and technology integration, setting a path for more impactful and accessible studies.

Increased Diversity in Trials

The VA is actively working to improve inclusion of women, LGBTQ+ individuals, and racial minorities in its studies. Women currently make up only 10% of veteran trial participants, although they represent 18% of the veteran population.

Integration of Artificial Intelligence

Machine learning tools are being tested to pre-screen patient eligibility, improve recruitment, and personalize treatment protocols based on large patient datasets.

Decentralized and Remote Trials

Telemedicine-capable clinical trials decrease the need for in-person visits and improve access for veterans in rural or medically underserved areas.

Greater Collaboration with Civilian Institutions

Partnerships with academic medical centers and private sector sponsors are expected to increase. These collaborations will expand the scope of treatments tested and accelerate drug approvals.

National Policy Support

Initiatives like the Precision Medicine Initiative and expanded VA budget allocations are helping scale research capacities. In FY 2023, the VA’s Medical and Prosthetic Research program received over $900 million in funding.

As the veteran population ages and faces sharper healthcare challenges, research initiatives that center veterans will become even more critical to advancing American medicine. The Veterans Research Foundation Pittsburgh is well positioned to lead that charge.