What could compromise the results of a randomized controlled trial (RCT) vaccine study conducted exclusively in pediatric patients at a hospital?

Selection Bias is the Primary Threat to This Study's Validity

Conducting an RCT exclusively in hospitalized pediatric patients introduces significant selection bias (Option A), as the study population is not representative of the broader pediatric population and enrollment is restricted to those already receiving hospital care. 1, 2

Why Selection Bias Compromises These Results

Restricted Population Sampling

• Hospital-based recruitment fundamentally limits generalizability because hospitalized children represent a selected subset with potentially more severe illness, different socioeconomic backgrounds, or specific access-to-care patterns compared to community-dwelling children 2
• The study population may systematically differ from the target population for vaccine implementation, as hospitalized patients often have comorbidities or clinical characteristics that influenced their hospitalization in the first place 3
• Selection bias related to "selection of representative subjects" directly impairs the ability to generalize study results to the broader pediatric population who would receive this vaccine in real-world settings 3

Enrollment Mechanism Concerns

• Even with randomization, if the recruitment process itself is biased toward certain patient types within the hospital, the internal validity suffers 4, 5
• Hospital-based studies face inherent selection pressures where only patients with access to that specific facility, insurance coverage, or disease severity requiring hospitalization can participate 1
• The lack of community-based enrollment means children with milder disease presentations, different ethnic backgrounds, or varying healthcare access patterns are systematically excluded 1

Impact on Study Validity

• Selection bias can distort treatment effect estimates even in properly randomized trials when the study population is fundamentally unrepresentative 6
• Studies with restricted populations (such as single-hospital cohorts) may not reflect real-world effectiveness because the baseline characteristics, disease severity, and response patterns differ from the general population 2
• The "good results" observed may not replicate in broader populations due to effect modification by unmeasured factors that differ between hospitalized and community populations 1

Why Recall Bias is Not the Answer

Recall bias (Option B) is irrelevant in this RCT context because:

• Recall bias applies to retrospective studies where participants must remember past exposures or events 1
• In a prospective RCT with predetermined endpoints and real-time data collection, recall of past events is not a primary data source 2
• Vaccine studies typically measure objective outcomes (antibody titers, infection rates, adverse events) documented prospectively, not recalled retrospectively 2

Critical Implications for Interpreting Results

• Single-center trials, particularly those in specialized settings like hospitals, frequently fail to replicate in multicenter studies due to local effects, minimal patient heterogeneity, and selection factors 1
• The positive findings should be interpreted with extreme caution before implementation, as hospital-based pediatric populations may respond differently than the general pediatric population receiving vaccines in outpatient settings 1
• External validity is severely compromised when eligibility is restricted to hospitalized patients, limiting the applicability of findings to routine vaccination programs 1, 2