Regulatory

Top 5 Statistical Analysis Tips for Successful EFSA Health Claims | Atlantia Blogs

Written by Shauni Fitzgerald | May 17, 2024 1:29:05 PM

In recent years, EFSA (European Food Safety Authority) opinions have placed a greater emphasis on the statistical analysis and methodology used in studies supporting health claims. This blog explores 5 crucial statistical considerations that can make or break the success of your health claim application.

Table of Contents



 

Power Calculations: The Foundation of Study Design

Power calculations are essential in designing robust studies. They provide the backbone for your hypothesis and help determine the sample size needed.


Why Power Calculations Matter

Power calculations ensure your study has enough participants to detect a meaningful effect. Without them, your study might lack credibility.


Documenting Power Calculations

Always document and report your power calculations. If not reported, authorities like EFSA may assume they were not performed.


Primary Endpoint Focus

Power calculations should focus on the primary endpoint. Claims based on secondary endpoints without corresponding power calculations risk rejection.


Case Study: 2017 Health Claim

In 2017, a health claim was rejected because the power calculation was based on a secondary endpoint. This highlighted the importance of aligning power calculations with primary endpoints.


Randomization: Ensuring Balanced Groups

Randomization is a critical process in study design. It helps create balanced groups, reducing bias and enhancing the reliability of your results.


Importance of Randomization

Randomization allocates subjects to groups without bias. This balance is crucial, especially at the study's baseline.


Effects of Poor Randomization

Poor randomization can lead to unbalanced groups, skewing results. This was evident in a 2021 EFSA review of a health claim for a grapeseed extract.


Case Study: Meganatural Health Claim

In 2021, EFSA discounted a health claim for Meganatural due to unbalanced groups at baseline. This imbalance was linked to a flawed randomization process.


Group Imbalances

  • Systolic BP: 134/83 vs. 123/74
  • Only 27 subjects in total

The imbalance in blood pressure readings between groups highlighted the randomization failure, leading to the study's exclusion.


Validated Measures: The Importance of Appropriate Assessments

Using validated measures is a cornerstone of credible research. It ensures that the tools used to measure outcomes are suitable for the population and condition being studied.


Why Validation Matters

Validation is about proving that a measure is appropriate for detecting change in a specific condition and target population. Without validation, the reliability of your study's outcomes is compromised.


Common Validation Pitfalls

One common mistake is using an outcome measure validated in one population and assuming it works for another. This can lead to inaccurate results and study rejection.


Case Study: Yestimune

In 2013, a claim for Yestimune, a product aimed at defending against upper respiratory tract infections, was rejected. The reason? The studies used an unvalidated questionnaire for common cold symptoms.


  • Three studies were discounted
  • Wisconsin Upper Respiratory Tract Symptom Questionnaire was not used

This example underscores the importance of using established, validated measures rather than creating new, untested ones.


Another Example: Lactobacillus Cassii Strain

A 2010 opinion on Lactobacillus Cassii strain highlighted similar issues. The studies used an unvalidated questionnaire for common cold symptoms.

Additionally, the study was underpowered, further weakening the credibility of the findings. These examples show that both validation and power calculations are crucial for robust research.


Multiplicity: Handling Multiple Endpoints Appropriately

Multiplicity is another critical aspect of study design. Properly handling multiple endpoints ensures that your findings are statistically significant and not just due to chance.


Understanding Multiplicity

Multiplicity refers to having multiple primary or secondary endpoints in a study. Adjustments must be made to account for the increased likelihood of finding a significant result by chance.


Adjusting for Multiple Endpoints

When you have multiple endpoints, you need to adjust your statistical analysis. This adjustment ensures that your findings are credible:


  • Use a hierarchy of outcomes
  • Adjust p-values for multiple endpoints

How to Adjust P-Values

If you have more than one primary endpoint, you must adjust the p-value for significance. For example, if the first endpoint's p-value is 0.05, the second should be 0.025, and so on.

This method ensures that your findings are not just due to random chance. Proper adjustment is crucial for the credibility of your study.


Case Study: Menaq7

In 2020, a claim for Menaq7, aimed at improving arterial elasticity, was rejected. The studies had multiple primary and secondary endpoints without any correction for multiplicity.


  • No hierarchy of outcomes
  • No correction for repeated measures

As a result, the panel deemed the statistical analysis inappropriate, and no conclusions could be drawn. This example highlights the importance of proper multiplicity handling in study design.

In conclusion, validated measures and proper handling of multiplicity are essential for robust and credible research. These elements ensure that your study findings are reliable and not just due to chance, ultimately strengthening your health claim application.


The Statistical Analysis Plan: A Roadmap to Success

The Statistical Analysis Plan (SAP) is a critical document that can significantly impact the success of your research. It outlines the intent and methodology of your statistical analysis before the study begins.


What is the SAP?

The SAP is a prospective document created before the active phase of the study concludes. It details the planned statistical methods and analyses.


Components of the SAP

The SAP includes key elements such as:


  • Populations to be analyzed
  • Definitions of intent-to-treat and per-protocol populations
  • Outcome measures

Importance of Timing

The SAP must be documented and agreed upon before the database is locked and unblinded. This timing helps avoid bias and ensures transparency.


Case Study: 2017 Amino Acid Beverage Claim

In 2017, EFSA requested the SAP for an amino acid beverage claim. The SAP was dated after the study had completed, and only the per-protocol population showed positive results, undermining the study's credibility.

An SAP is essential for maintaining the integrity of your research. It demonstrates that you have planned your analyses in advance, reducing the risk of bias and increasing the credibility of your findings.

 

Key Takeaways

  1. Power Calculations: Ensure studies have adequate power calculations focused on primary endpoints to avoid credibility issues.
  2. Randomization: Implement proper randomization to maintain balanced groups and reduce bias.
  3. Validated Measures: Use validated outcome measures suitable for the target population to ensure reliable results.
  4. Multiplicity Handling: Adjust for multiple endpoints to maintain statistical significance and credibility.
  5. Statistical Analysis Plan (SAP): Develop a comprehensive SAP before study completion to outline intended analyses and prevent bias.

 



 

FAQ

Here are some frequently asked questions about the statistical considerations in health claims.


What is the primary goal of power calculations?

Power calculations aim to determine the sample size needed to detect a meaningful effect in your study. They ensure your study has enough participants to produce credible results.


Why is randomization crucial in study design?

Randomization helps create balanced groups, reducing bias and enhancing the reliability of your results. It ensures that subjects are allocated to groups without bias.


What happens if validated measures are not used?

Using unvalidated measures can compromise the reliability of your study's outcomes. It's crucial to use measures validated for the specific population and condition being studied.


How should multiple endpoints be handled?

Proper handling of multiple endpoints involves adjusting your statistical analysis to account for the increased likelihood of finding a significant result by chance. This can include adjusting p-values and creating a hierarchy of outcomes.


Why is a Statistical Analysis Plan important?

The SAP outlines the intent and methodology of your statistical analysis before the study begins. It helps avoid bias and ensures that your analyses are transparent and credible.

Understanding these statistical considerations is vital for the success of your health claim application. Proper planning, execution, and documentation can significantly enhance the credibility of your research.