Call for authors - Developing a systematic review on accuracy and precision of data collection and analytical methods for haemoglobin assessment in populations

Deadline of submission: 15 August 2023

4 July 2023
Call for authors

The World Health Organization (WHO) Department of Nutrition and Food Safety is aiming to comprehensively review and analyze available evidence on data collection and analytical methods for the assessment of haemoglobin concentration. This work will help to inform recommendations for sample collection and analysis when assessing haemoglobin in individuals and populations and will inform national and global monitoring, programme planning and decision-making.

Background

Anaemia is an indicator of overall health and WHO monitors the global prevalence of anaemia in women and children through periodically developing global estimates(1).  

Haemoglobin concentration is the most commonly used biomarker to diagnose anaemia. It is measured from whole blood (venous or capillary), most often obtained from venipuncture or finger- or heel-stick.

The cyanmethemoglobin method has been internationally recognized as the reference standard method for the determination of the haemoglobin and has been recommended for the calibration of automated haematology analyzers and point-of-care haemoglobinometers (4, 5, 6. 7). Venous blood assessed by automated haematology analyzers is comparable with the cyanmethemoglobin method, hence has also been considered as the gold standard for haemoglobin determination (8).

In field settings, capillary blood assessed on point-of-care haemoglobinometers is the most common field protocol. However, differences in haemoglobin concentration have been observed when comparing different sources of blood - such as single-drop capillary, pooled drops of capillary, or venous blood - and also when comparing the same source of blood across and within devices (4, 8-11).

Pre-analytical, analytical and post-analytical factors may also influence the measurement of biomarkers. These are further influenced by human and analytical errors, biological differences, method of analysis, type and management of equipment, etc.  Factors that are known to impact haemoglobin concentration include age, sex, source of whole blood, postural position of the patient/subject, analytical method of assessment, equipment calibration, and environmental conditions such as temperature and humidity (8).

Haemoglobin values are used in both the clinical and population/public health settings. They may be used to screen for anaemia, identifying individuals and populations at risk that require prevention and treatment, as well as to monitor the response of an individual or population to an intervention. Therefore, haemoglobin assessment methods must be precise and accurate and should take into consideration preanalytical, analytical and post-analytical factors affecting or influencing its assessment.

Scope

The WHO Department of Nutrition and Food Safety aims to set evidence-informed recommendations for the measurement of haemoglobin in individuals and populations based on a comprehensive review and meta-analysis of available evidence.

WHO is seeking support from individuals/group of experts with relevant expertise and experience to systematically review the evidence on accuracy and precision in methods for the assessment of haemoglobin concentration.

WHO is thus commissioning a systematic review to retrieve, synthesize, and assess all available evidence for the following comparisons:

  1. Blood source comparisons
    • Venous blood (gold standard) vs single drop capillary blood, measured on an automated haematology analyzer (gold standard)
    • Venous blood (gold standard) vs pooled capillary blood, measured on an automated haematology analyzer (gold standard)
    • Single drop capillary blood vs pooled capillary blood measured on an automated haematology analyzer (gold standard)
  2. Devices comparisons
    • Automated haematology analyzer (gold standard) vs HemoCueTM using venous blood (gold standard), stratified by brand and model of haemoglobinometer (e.g. HemoCueTM Hb, HemoCueTM 201+, HemoCueTM 301, other brand and model)
    • Automated haematology analyzer (gold standard) vs HemoCueTM using single drop capillary blood, stratified by brand and model of haemoglobinometer (e.g. HemoCueTM Hb, HemoCueTM 201+, HemoCueTM 301, other brand and model)
    • Automated haematology analyzer (gold standard) vs HemoCueTM using pooled capillary blood, stratified by brand and model of haemoglobinometer (e.g. HemoCueTM Hb, HemoCueTM 201+, HemoCueTM 301, other brand and model)

The selected team will aim to assess variations in measurement, diagnosis, uncertainty and different types of error in haemoglobin measurement. Authors will summarize their findings and provide their views on the most accurate and precise data collection and analytical methods to measure haemoglobin. Additionally, preanalytical, analytical and post-analytical factors available in identified publications must be considered in the analyses. A non-comprehensive list of factors includes:

  • Preanalytical: data collection setting (clinical laboratory or field), fasting state at time of blood collection, order and time between blood draw and finger prick, location (arm/finger) from which blood is obtained, postural position at time of blood collection (standing/sitting/laying down), training of technician collecting blood sample, equipment used to take blood sample (type and/or size of needle and lancet), time between blood sample collection and analysis, storage conditions of blood sample, age and sex of subjects, pregnancy status of subject(s), air temperature and humidity
  • Analytical: calibration of equipment, quality control procedures and training of laboratory technicians.
  • Post-analytical: validation of results, data analysis, data interpretation, data reporting

How to apply?

Interest in conducting this review must be expressed through submission of a proposal that covers all proposed comparisons of haemoglobin assessment.

Applicants are encouraged to form a team with expertise in biochemistry, haematology, programme implementation, statistics and systematic review methods.

Deadline for application is 16:00 o’clock Tuesday 15th August 2023 (Central European Time) thus only applications received before that time will be considered.

Kindly send your proposals to the following e-mail address nfsdata@who.int with the email subject "Proposal systematic review haemoglobin".

Required information:

  • Contact information for the main focal point only (i.e. Lead Investigator)
  • Cover letter/statement of motivation, including a maximum of 600 words detailing why your team is submitting this Expression of Interest, and why you believe your team is the most suitable to undertake this work. Letter must highlight interested author’s/team’s relevant experience with conducting complex reviews, including the most relevant references of reviews that they have published in peer-reviewed journals.  Only apply if you and your team have this experience and expertise.
  • Proposed fee for undertaking the work (in USD)
  • Ideal start date and completion dates to undertake the work (within the timeline proposed)
  • ONE document (ideally in PDF format) that includes all Curriculum Vitae (CV) of the proposed research team, highlighting key references to relevant reviews.
  • ONE document (ideally in PDF format) that includes a brief biography of each research team member (max 150 words per person).
  • The proposal should outline the background and justification for the review, search strategy and databases to be searched, inclusion/exclusion criteria, specific data they will extract from each study (ie. individual-level data), process of data extraction and analytical approach. This description should reflect the scope of work described above. Author(s) teams should demonstrate capacity to conduct the review(s) within the timeline indicated below, and accessibility to required publications. Successful authors will be required to submit a protocol prior to performing the review. 
  • Send your proposals to the following e-mail address nfsdata@who.int with the email subject"Proposal systematic review haemoglobin".

15 August 2023 – Interested authors or teams submit proposals and budget to WHO

WHO review of proposals complete, and authors/teams contacted, and contracts agreed (subject to WHO conditions including review of declarations of interest to members of the review teams) by September 2023

31 October 2023 – Protocol submitted to PROSPERO

29 February 2024 – Draft review submitted to WHO

References

  1. WHO Global Health Observatory. Global Anaemia estimates, 2021 Edition. Geneva: Global Health Observatory, 2022.
  2. World Health Organization.  Comprehensive Implementation Plan on Maternal IaYCNGWHO, 2014.
  3. World Health Organization. Nutritional anaemias: tools for effective prevention and control. Geneva: World Health Organization; 2017. Licence: CC BY-NC-SA 3.0 IGO.
  4. Whitehead RD, Mei Z, Mapango C, Jefferds MED. Methods and analyzers for hemoglobin measurement in clinical laboratories and field settings. Ann N Y Acad Sci. 2019;1450(1):147-71.
  5. Karakochuk CD, Hess SY, Moorthy D, Namaste S, Parker ME, Rappaport AI, et al. Measurement and interpretation of hemoglobin concentration in clinical and field settings: a narrative review. Ann N Y Acad Sci. 2019;1450(1):126-46.
  6. Centers for Disease Control and Prevention, World Health Organization, Nutrition International,  UNICEF.       Micronutrient survey manual. Geneva: World Health Organization; 2020. Licence: CC BY-NC-  SA 3.0 IGO .
  7. Cakmak I, Kalayci M, Ekiz H, Braun HJ, Kilinc Y, Yilmaz A. Effect of Zinc and Iron-Deficiency on Phytosiderophore Release in Wheat Genotypes Differing in Zinc Efficiency.
  8. Neufeld LM, Larson LM, Kurpad A, Mburu S, Martorell R, Brown KH. Hemoglobin concentration and anemia diagnosis in venous and capillary blood: biological basis and policy implications. Ann N Y Acad Sci. 2019;1450(1):172-89.
  9. Stevens GA, Flores-Urrutia MC, Rogers LM, Paciorek CJ, Rohner F, Namaste S, et al. Associations between type of blood collection, analytical approach, mean haemoglobin and anaemia prevalence in population-based surveys: A systematic review and meta-analysis. J Glob Health. 2022;12:04088.
  10. Chugh V, Dhaliwal HS. Biofortification of Staple Crops. Bhullar GS, Bhullar NK, editors. San Diego: Elsevier Academic Press Inc; 2013. 177-96 p.
  11. Rappaport AI, Karakochuk CD, Hess SY, Whitehead RD, Jr., Namaste SML, Dary O, et al. Variability in haemoglobin concentration by measurement tool and blood source: an analysis from seven countries. J Clin Pathol. 2021;74(10):657-63.
  12. Larson LM, Braat S, Hasan MI, Mwangi MN, Estepa F, Hossain SJ, et al. Preanalytic and analytic factors affecting the measurement of haemoglobin concentration: impact on global estimates of anaemia prevalence. BMJ Glob Health. 2021;6(7).
  13. De la Salle B. Pre- and postanalytical errors in haematology. Int J Lab Hematol. 2019;41 Suppl 1:170-6.