I thank Professor Colquhoun for taking the time to comment on our work. I am happy to be able to reassure him that there was no breakdown in the editorial process, and that – unlike the accompanying editorial – our article was subjected to independent peer review.
As Professor Colquhoun will be aware, absolute risk reduction is commonly represented by presenting the ‘Number needed to treat’ (NNT) (the inverse of the absolute risk reduction), which in the case of our study represents the average number of people who need to take a vitamin D supplement in order to prevent one individual from having at least one acute respiratory infection (ARI). I draw his attention to the panel on the bottom left of page 1 of the article, where NNT data are presented. The 2% absolute risk reduction alluded to by Avenell and Bolland is a raw value. More accurate estimates of absolute effect size for the study population as a whole are generated from adjusted odds ratios (aOR) as presented in the summary of findings table (supplementary Table S3), which shows a reduction in risk of having at least one ARI from 42.2% to 39.1% using the adjusted odds ratio (aOR) of 0.88 generated by the one-step IPD meta-analysis. Using the aOR from the two-step IPD meta-analysis (0.80, 95% CI 0.69 to 0.93), the absolute risk reduction is from 42.2% to 36.9%. The corresponding NNTs are 33 for the estimate from one-step IPDMA and 19 for the estimate from two-step IPDMA. To put these numbers into context, Cochrane reviews report the NNT to prevent one influenza-like illness with parenteral inactivated influenza vaccine to be 40 in adults (1) and 28 in children (2). Influenza vaccination programmes are motivated by the principle that when a disease is common, even minor reductions in incidence can have significant public health benefits; vitamin D fortification programmes might well be motivated by the same principle, particularly given that ARI is a major cause of industrial absenteeism, health service use and antibiotic prescribing (3). Approximately 30% of the UK population is estimated to be vitamin D deficient in winter and spring (4) – in this group the NNT with daily/weekly vitamin D supplementation to prevent one ARI falls to four. This represents a large protective effect by any standards.
I am fully in agreement with Professor Colquhoun that the press are responsible for the publicity this article has received. I can only presume that this is because the statistics above suggest that our findings are of potential importance for public health.
1. Demicheli V, Rivetti D, Deeks JJ, Jefferson TO. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2004(3):CD001269.
2. Jefferson T, Rivetti A, Di Pietrantonj C, Demicheli V, Ferroni E. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev. 2012(8):CD004879. Epub 2012/08/17.
3. Fendrick AM, Monto AS, Nightengale B, Sarnes M. The economic burden of non-influenza-related viral respiratory tract infection in the United States. Arch Intern Med. 2003;163(4):487-94. Epub 2003/02/18.
4. Cashman KD, Dowling KG, Skrabakova Z, Gonzalez-Gross M, Valtuena J, De Henauw S, et al. Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr. 2016;103(4):1033-44. Epub 2016/02/13.
Competing interests:
I am the corresponding author of the paper on which Professor Colquhoun has commented.
Rapid Response:
Re: Author's response to Professor Colquhoun
I thank Professor Colquhoun for taking the time to comment on our work. I am happy to be able to reassure him that there was no breakdown in the editorial process, and that – unlike the accompanying editorial – our article was subjected to independent peer review.
As Professor Colquhoun will be aware, absolute risk reduction is commonly represented by presenting the ‘Number needed to treat’ (NNT) (the inverse of the absolute risk reduction), which in the case of our study represents the average number of people who need to take a vitamin D supplement in order to prevent one individual from having at least one acute respiratory infection (ARI). I draw his attention to the panel on the bottom left of page 1 of the article, where NNT data are presented. The 2% absolute risk reduction alluded to by Avenell and Bolland is a raw value. More accurate estimates of absolute effect size for the study population as a whole are generated from adjusted odds ratios (aOR) as presented in the summary of findings table (supplementary Table S3), which shows a reduction in risk of having at least one ARI from 42.2% to 39.1% using the adjusted odds ratio (aOR) of 0.88 generated by the one-step IPD meta-analysis. Using the aOR from the two-step IPD meta-analysis (0.80, 95% CI 0.69 to 0.93), the absolute risk reduction is from 42.2% to 36.9%. The corresponding NNTs are 33 for the estimate from one-step IPDMA and 19 for the estimate from two-step IPDMA. To put these numbers into context, Cochrane reviews report the NNT to prevent one influenza-like illness with parenteral inactivated influenza vaccine to be 40 in adults (1) and 28 in children (2). Influenza vaccination programmes are motivated by the principle that when a disease is common, even minor reductions in incidence can have significant public health benefits; vitamin D fortification programmes might well be motivated by the same principle, particularly given that ARI is a major cause of industrial absenteeism, health service use and antibiotic prescribing (3). Approximately 30% of the UK population is estimated to be vitamin D deficient in winter and spring (4) – in this group the NNT with daily/weekly vitamin D supplementation to prevent one ARI falls to four. This represents a large protective effect by any standards.
I am fully in agreement with Professor Colquhoun that the press are responsible for the publicity this article has received. I can only presume that this is because the statistics above suggest that our findings are of potential importance for public health.
1. Demicheli V, Rivetti D, Deeks JJ, Jefferson TO. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev. 2004(3):CD001269.
2. Jefferson T, Rivetti A, Di Pietrantonj C, Demicheli V, Ferroni E. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev. 2012(8):CD004879. Epub 2012/08/17.
3. Fendrick AM, Monto AS, Nightengale B, Sarnes M. The economic burden of non-influenza-related viral respiratory tract infection in the United States. Arch Intern Med. 2003;163(4):487-94. Epub 2003/02/18.
4. Cashman KD, Dowling KG, Skrabakova Z, Gonzalez-Gross M, Valtuena J, De Henauw S, et al. Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr. 2016;103(4):1033-44. Epub 2016/02/13.
Competing interests: I am the corresponding author of the paper on which Professor Colquhoun has commented.