Identify Biomarkers in Migraine and Cluster Headache by Improving Experimental Design

Simona Denise Frederiksen, PhD, MS

AHSAM 2020 - Oral session
Published on October 2, 2020 | NEW


4 minute read

Key messages

  • Researchers have attempted to identify biomarkers in the headache field for decades.
  • In order to improve success in biomarker discovery, researchers need to consider what leads to variability between study outcomes.
  • Improved understanding of confounding factors that influence outcomes will inform future study design.
  • Sex distribution, age, aura, menstrual cycle, study quality, specimen source, blood specimen, and blood sampling site and timing have been identified as potential confounders.1,2
  • Standardization and multivariate analyses are methods that could lead to a better understanding of confounding factors and improve biomarker discovery.

Key messages

  • Researchers have attempted to identify biomarkers in the headache field for decades.
  • In order to improve success in biomarker discovery, researchers need to consider what leads to variability between study outcomes.
  • Improved understanding of confounding factors that influence outcomes will inform future study design.
  • Sex distribution, age, aura, menstrual cycle, study quality, specimen source, blood specimen, and blood sampling site and timing have been identified as potential confounders.1,2
  • Standardization and multivariate analyses are methods that could lead to a better understanding of confounding factors and improve biomarker discovery.

Background

What do we already know about this topic?

  • Researchers have attempted to identify biomarkers in the headache field for decades.
  • The majority of research has focused on migraine with little attention paid to cluster headache.
  • The diagnostic criteria for migraine and cluster headache are distinct but biochemical levels similar.
  • As yet, no biomarkers have been established in clinical practice, but calcitonin gene-related peptide (CGRP) is currently the most promising candidate.

Summary

Success in biomarker discovery?

  • In order to improve success in biomarker discovery, researchers need to consider the variability between studies that has led to inconsistent findings and irreproducibility.
  • Within- and between-study variabilities have resulted in estimates with low precision, false negatives and false positives, and non-repeatability.
  • The focus of current research should be adjusted to broaden the scope outside of a limited number of biochemical compounds.

How to better recognize confounders

  • Taking CRGP as a potential biomarker, a full literature search should be conducted to identify all available evidence that investigates factors that affect CRGP levels.
  • Overall, a better understanding of confounding factors is of importance for the design of future studies investigating exposure associations.
  • Sex distribution, age, aura, menstrual cycle, study quality, specimen source, blood specimen and blood sampling site and timing were identified as potential confounders.1,2
  • Further studies are needed to confirm they are potential confounders.

How to control for confounding factors

  • Restriction, matching and randomization are methods often employed by investigative studies to control for confounding factors but there are often consequences to employing these methods.
  • Standardization and multivariate analyses are methods that could lead to a better understanding of confounding factors and improve biomarker discovery.

 

Table: How to control for confounding factors

Conclusions

  • The systemic and meta-analysis carried out by Frederiksen SD, et al1  revealed a need to (i) identify and validate confounders underlying signaling molecule fluctuations, (ii) select a biological material where less variation is observed, (iii) develop standardized criteria on how to report findings on cluster headaches, and (iv) establish guidelines related to the conduct of these types of studies.

This is a highlights summary of an oral session given at the AHSAM 2020 Virtual Annual Scientific Meeting and presented by:

Simona Denise Frederiksen, PhD, MS
University of Calgary, Cumming School of Medicine
Calgary, Alberta

The content is produced by Infomedica, the official reporting partner of ASHAM 2020 Virtual Annual Scientific Meeting. The summary text was drafted by Goldcrest Medical Writing, reviewed by Marco Vercellino, MD, an independent external expert, and approved by Jessica Ailani, MD, FAHS and Mark J. Burish, MD, PhD, the scientific editors of the program.

The presenting authors of the original session had no part in the creation of this conference highlights summary.

1. Frederiksen SD, Bekker-Nielsen Dunbar M, Snoer AH, et al. Serotonin and neuropeptides in blood from migraine and cluster headache patients in case-control and case-crossover settings: A systematic review and meta-analysis. Headache 2020;60:1132-1164.

2. Frederiksen, S.D. Promote Biomarker Discovery by Identifying Homogenous Primary Headache Subgroups. Headache: The Journal of Head and Face Pain 2019;59:797-801.



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