Internal and external study validity

Study Sample & Validity

• Large random sample comprising 47,867 men, mitigating selection bias.
• Mediterranean diet assessed via self-reported food intake questionnaires, which may introduce measurement error in exposure assessment.
• Prostate cancer outcomes sourced from national registries and hospital records, minimizing measurement error in outcome assessment.

Internal Validity & Confounding

• Internal validity compromised by potential information bias in exposure variables.
• Confounding occurs when a third factor potentially distorts the association between exposure and outcome.
• Impacts of confounding include:
  • Distortion of exposure-outcome relationships.
  • Creation of false associations.
  • Masking of true associations.
  • Misestimation of association strength (overestimation/underestimation).

Assessing Confounding Impact

• Expect some degree of confounding in observational studies due to non-experimental conditions.
• Consider confounding effects when:
  • Unexpected results arise contrary to prior evidence.
  • Biological sense is lacking.

Minimizing Confounding Effects

• Ensure sample representation of specific population subgroups (e.g., >65 years old, male smokers, university students).
• Avoid generalizing findings to the general population; specific assumptions apply when generalizing to similar populations.

External Validity Considerations

• Study conducted among male Health Professionals in the US, not representative of the general population.
• Findings may generalize to Health Professionals in similar countries, particularly in Western nations.
• Flexibility in generalizing results increases when investigating biological mechanisms.

Conclusion on Study Validity

• Evaluate the following in determining internal validity:
  • Chance (random/sampling error).
  • Bias (systematic error).
  • Confounding (uncontrolled third factors).

Role of Chance in Findings

• Random sampling inevitably introduces chance; errors can skew results.
• Statistical significance assessed through p-values and 95% confidence intervals indicates reliability of findings.
• Caution warranted if confidence intervals are wide, affecting estimate precision.

Adjusting for Confounders

• Identify potential confounders pre-study using literature, clinical expertise, and subject knowledge.
• Adjust for confounders during data analysis to derive confounder-adjusted estimates.
• Despite adjustments, residual confounding can persist due to unknown confounders or inaccuracies in assessing known ones.

Identified Confounding Factors

• Study adjusted for key confounders including:
  • Age and Body Mass Index (BMI).
  • Physical activity levels.
  • Smoking status and ethnicity.
  • Height, diabetes, family history of prostate cancer, and vitamin supplement use.
• While major confounders were addressed, some residual confounding may still affect internal validity but is unlikely to be significant due to careful adjustments.

Evaluate the internal validity of a study on the Mediterranean diet and its relation to prostate cancer. The study has a large random sample, but potential measurement errors may affect the results. Identify the limitations of the study and their impact on the findings.