Impact of the Choosing Wisely Campaign on Folate Test Utilization: An Observational Study in a National Reference Laboratory

To the Editor:

Aiming to reduce medical interventions offering marginal clinical benefits, the Choosing Wisely^TM Campaign launched in 2012 encouraged medical societies to identify tests or treatments whose necessity should be questioned (1). The American Society of Clinical Pathology (ASCP) has represented the laboratory since the inception of this campaign, publishing 35 recommendations on tests offering limited value to patient care (2). This study focuses on the impact of the Choosing Wisely campaign on folate test utilization using data from a large national reference laboratory over a 10-year period. Folate is essential in DNA synthesis and repair and its deficiency can lead to fetal neural tube defects (NTDs), macrocytic anemia, and neurological symptoms (3). The general population deficiency has declined appreciably since the 1998 US mandate requiring folate fortification in processed grains to address deficiency and prevent NTDs in newborns (4). Folate status can be evaluated through serum or red blood cell (RBC) folate measurements. In September 2017 the ASCP recommended direct treatment in suspected deficiency cases instead of testing, and further indicated that RBC folate testing should not be ordered as it adds no value to diagnosis or treatment (2).

This study was exempt from Institutional Review Board. Specimens with serum and/or RBC folate tests were retrieved from Labcorp^® diagnostics database from January 1, 2013 to December 31, 2023 (serum folate; n = 40 million results approximately, RBC folate; n = 860 000 results approximately). Testing was performed using Roche cobas serum or RBC folate methods at various US testing locations, serving patients in the Northeast (NE), South (S), Midwest (M), and West (W) regions as defined by the US Census Bureau. Data were aggregated by year and standardized against 2 tests commonly ordered with folate to normalize variations in testing volume: complete blood count (CBC) or vitamin B₁₂ (B₁₂) tests ordered during the same period. The data was further split into pre-Choosing Wisely (2013–2017) and post-Choosing Wisely (2018–2023) periods and normalized volumes were used to determine annualized change within each period: $((VolumeinfinalyearIntialVolume)1timeperiod)−1$⁠. The Mann–Kendall trend test was performed per period to determine statistical significance (P < 0.05). Data analyses were performed in Python (v.3.10.6) using Amazon SageMaker Studio. Libraries included pandas (v.2.2.2), matplotlib (v.3.8.4), seaborn (v.0.13.2), pymannkendall (v.1.4.3), and SciPy (v.1.13.0).

The relative percentages of samples representing the NE, M, S, and W remained steady across the pre- and post-Choosing Wisely periods: RBC folate; pre-Choosing Wisely—15.5%, 10.8%, 58.4%, and 15.3%, respectively; post-Choosing Wisely—15.5%, 11.7%, 54.0%, and 18.8%, respectively; Serum folate: pre-Choosing Wisely—20.5%, 6.0%, 55.7%, and 17.9%, respectively; post-Choosing Wisely—18.8%, 6.4%, 56.2%, and 18.7%, respectively. Normalization against both CBC and B₁₂ revealed a decreasing trend in RBC folate test utilization during the pre-Choosing Wisely period with an annualized decrease of 3.2% (P < 0.05) and 4.9% (P < 0.05), respectively. A decreasing trend was observed in the post-Choosing Wisely period with an annualized decrease of 5.5% and 9.8%, respectively (P < 0.05) (Fig. 1A). By contrast, serum folate utilization exhibited no trend during the pre-Choosing Wisely period (P > 0.05) when normalized to CBC. A 4.8% annualized increase in utilization was observed in the post-Choosing Wisely period (P > 0.05) (Fig. 1B). Normalization with B₁₂ showed a decreasing trend during the pre-Choosing Wisely period (P < 0.05) with an annualized decrease of 1.3% while no trend was observed in the post-Choosing Wisely period (P > 0.05).

Fig. 1.

Trends in folate testing (2013–2023). (A), RBC folate testing showed a decline in the pre-Choosing Wisely period that accelerated in the post-Choosing Wisely period based on comparing annualized change with CBC normalization (solid line) or B₁₂ normalization (dashed line); (B), Serum folate testing showed no trend with CBC normalization (solid line) but a decrease with B₁₂ normalization (dashed line) in the pre-Choosing Wisely period. An increase in utilization was observed with CBC normalization and no change observed with B₁₂ normalization in the post-Choosing Wisely period. The dashed vertical line represents when Choosing Wisely for folate was published.

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In our cohort we observed an increased reduction in RBC folate utilization after the ASCP Choosing Wisely recommendation. Interestingly, the impact on serum folate testing is unclear as the data normalized to CBC showed an upward trend but normalization to B₁₂ showed no change. These trends may have been influenced by changes in physician ordering patterns for CBC or B₁₂ or if practice changes occurred, they may have been too small to be captured in this type of analysis.

Regardless of whether serum folate orders have increased or remained unchanged post-Choosing Wisely, the lack of the intended effect of the campaign may be due to several reasons. Implementing guidelines and recommendations can be challenging, requiring strategic intervention techniques by healthcare organizations and resources to have a sustained effect. There is also the question of stark deficiency (risk of megaloblastic anemia) vs insufficiency (risk of NTDs) that maybe driving utilization in some patient populations. While both deficiency and insufficiency have decreased postfortification, the 2019 NHANES study on folate fortification spanning 1999–2016 reported insufficiency rates averaging at approximately 20% and disparities noted in women of certain ethnic groups (4). The authors of this study recommend continued monitoring to improve these gaps (4). Last, deficiency rates have been reported to be higher than the national average of <1% in localized communities lending support for laboratory monitoring of folate status (4, 5).

The strength of this analysis includes the use of millions of records over a decade with every US region represented, providing a nationwide view of serum and RBC folate test utilization. The study is limited by its retrospective design, reliance on de-identified laboratory data, and no information on patient-specific factors that may be influencing ordering patterns.

Nonstandard Abbreviations: ASCP, American Society of Clinical Pathology; NTDs, neural tube defects; RBC, red blood cell; NE, Northeast; S, South; M, Midwest; W, West; CBC, complete blood count; B₁₂, vitamin B₁₂.

Author Contributions:  The corresponding author takes full responsibility that all authors on this publication have met the following required criteria of eligibility for authorship: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. Nobody who qualifies for authorship has been omitted from the list.

Ato Aikins (Data curation-Lead, Formal analysis-Lead, Visualization-Lead, Writing—original draft-Supporting, Writing—review & editing-Supporting), Zahra Shajani-Yi (Conceptualization-Supporting, Writing—review & editing-Supporting), Sanjai Nagendra (Conceptualization-Supporting, Writing—review & editing-Supporting), David Alfego (Formal analysis-Supporting, Resources-Supporting, Supervision-Supporting), and Pratistha Ranjitkar (Conceptualization-Lead, Data curation-Lead, Writing—original draft-Lead, Writing—review & editing-Lead).

Authors’ Disclosures or Potential Conflicts of Interest:  Upon manuscript submission, all authors completed the author disclosure form.

Research Funding: None declared.

Disclosures: All authors are employed by Labcorp. Z. Shajani-Yi has received honoraria for presenting at annual meetings for the American Society for Clinical Pathology (ASCP) and Association for Diagnostics & Laboratory Medicine (ADLM, formerly AACC); has received travel support from ADLM, ASCP, and College of American Pathologists (CAP); and has stock or stock options as an employee of Labcorp. S. Nagendra received travel support paid to institution for the Patient-centered Laboratory Utilization Guidance Services (PLUGS) Annual Meeting 2024. D. Alfego has stock or stock options as an employee of Labcorp. P. Ranjitkar has stock or stock options as an employee of Labcorp.

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