Letter to the Editor: Clarification Required for Study Result Validation

To the Editor:

Kang et al. (January 16, 2024 issue, Journal of Korean Medical Science)1 proposed an alternative method for alert of seasonal influenza epidemics. The study compared the issuing time of influenza epidemic alert defined by the current Korea Disease Control and Prevention Agency (KDCA) method and the Time Derivative (TD) method for the past 10 influenza seasons in Korea.1

The authors explained that the KDCA uses the U.S. Centers for Disease Control and Prevention (CDC) formula for epidemic threshold calculation. However, there are differences between the two formulas in terms of the definition of non-influenza time period and the number of previous influenza seasons used for the calculation. The CDC defines the non-influenza period based on the weekly number of influenza-positive samples out of the season’s total number of influenza-positive samples, whereas the KDCA defines the period based on the weekly influenza-positive sample proportion out of the total respiratory samples collected during that week.2,3 Besides, the CDC uses previous two influenza seasons for the threshold calculation, but the KDCA uses previous three seasons (Table 1).2,3 Accordingly, it is unclear which method was adopted in the study for the comparison purpose.

Table 1. Epidemic threshold for seasonal influenza.

Agency	Epidemic threshold
KDCA	- [mean rate of ILI (per 1,000) during non-influenza weeks for the most recent three seasons + (2 × standard deviations)]
	- A non-influenza time period is defined as two or more consecutive weeks in which influenza positivity among respiratory laboratory samples is lower than 2%
CDC	- [mean percentage of ILI during non-influenza weeks for the most recent two seasons + (2 × standard deviations)]
	- A non-influenza time period is defined as two or more consecutive weeks in which each week accounted for less than 2% of the season’s total number of specimens that tested positive for influenza

KDCA = Korea Disease Control and Prevention Agency, CDC = Centers for Disease Control and Prevention, ILI = Influenza-Like Illness.

In addition, the authors used 2021–22 season, 2019–20 season, and 2018–19 season for the 2022–23 epidemic threshold calculation. In this calculation, 2021–22 season may not be eligible for inclusion as the author stated that there was no influenza epidemic for that season. This is also a contradiction to the introduction in the manuscript, where the authors stated that the ILI rate during past seasons when seasonal influenza epidemic occurred was used. We are curious about if the inclusion of 2017–18 season in place of 2021–22 season could lead to any change in the result.

We believe these factors could result in a bias in the study conclusion. Therefore, clarification would be required to increase generalizability and validity of the study result.

Authors’ Response to the Letter

Thank you so much for your comment. We truly appreciate your valuable feedback.

The author of the letter pointed out the difference between KDCA’s epidemic threshold calculation and the U.S. CDC’s calculation, based on the most up-to-date information from the CDC website. We agree that there are some differences between the two institutions. For your information, the KDCA epidemic threshold calculation method was originally adopted from the U.S. CDC method, and the definition of the non-influenza epidemic period was modified based on discussions at the influenza advisory meeting in 2016 (not published). It has been used without changes, but the U.S. CDC method has been constantly changing, especially after the COVID-19 pandemic (from 3 seasons to 2 seasons).3

Therefore, we would like to revise our article to clarify this issue.

(previous) The influenza epidemic alerts in Korea are issued using the same influenza epidemic formula as the U.S. Centers for Disease Control and Prevention (CDC) standard

(revised) The influenza epidemic alerts in Korea are issued based on the influenza epidemic formula, which was originally adopted from the U.S. Centers for Disease Control and Prevention (CDC) method in 2007. It was modified in terms of the definition of the non-influenza epidemic period in 2016, and it has been used without changes since then (not published).

The author of the letter also commented on the inclusion of the 2021–22 season in the epidemic threshold calculation for the 2022–23 season. The influenza epidemic threshold was decided based on the influenza advisory meeting in 2022. As there was no influenza epidemic in the previous two seasons (2020–21, 2021–22), the advisory group decided to maximize the sensitivity of the threshold to detect the epidemic as early as possible. They agreed on including the 2021–22 season, as the influenza virus was detected during this season, even if there was no seasonal epidemic. The option of using the 2017–18 season instead of the 2021–22 season was also discussed during the meeting, but it was not selected in the end.

For your information, if we use 2017–18 season instead of 2021–22 season for 2022–23 season epidemic threshold calculation, the threshold is 5.8 and the epidemic alert for KDCA method could have been in week 40, which is the same week with epidemic alert with TD method.

We found that there was some error in the discussion section, paragraph 2, and we would like to revise it.

(previous) If calculated based on the data from the 2021–2022 season, 2020–2021 season, and 2019–2020 season, using the existing influenza epidemic threshold formula, the epidemic threshold is 5.8.

(revised) If calculated based on the data from the 2017–2018 season, 2018–2019 season, and 2019–2020 season, using the existing influenza epidemic threshold formula, the epidemic threshold is 5.8.

Seul-Ki Kang¹, Bryan Inho Kim¹, and Woo-Sik Son²

¹Division of Infectious Disease Control, Bureau of Infectious Disease Policy, Korea Disease Control and Prevention Agency, Cheongju, Korea.

²Research Team for Transmission Dynamics of Infectious Disease, Division of Fundamental Research on Public Agenda, National Institute for Mathematical Sciences, Daejeon, Korea.

Address for Correspondence: Bryan Inho Kim, PhD. Division of Infectious Disease Control, Bureau of Infectious Disease Policy, Korea Disease Control and Prevention Agency, 187, Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju 258159, Republic of Korea. globalepi@korea.kr