An introduction to multiplicity issues in clinical trials: the what, why, when and how

Li, Guowei; Taljaard, Monica; Heuvel, Edwin R. van den; Levine, Mitchell; Cook, Deborah J.; Wells, George A.; Devereaux, P.J.; Thabane, Lehana

doi:10.1093/ije/dyw320

Cited by 229 publications

(235 citation statements)

References 60 publications

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“…Hence, the results from the present study should be interpreted cautiously. However, when interpreting these analyses, it is also imperative to consider that (a) multiplicity adjustments primarily apply to confirmatory hypotheses and corresponding analyses, not for exploratory analyses 22,50,51 ; (b) the lack of statistical power have limited us to handle the necessary α-adjustments, 50,51 and (c) the Hochberg procedure is more conservative and less powerful than other semi-parametric and parametric tests. 21,22 Some limitations need to be mentioned: (a) the crosssectional design of the study does not allow us to make causal inferences; (b) the results should be interpreted with caution given the small size of the studied sample; (c) only interested participants were involved in the study; (d) a selfreported survey was used to collect sociodemographic and clinical data.…”

Section: Discussionmentioning

confidence: 99%

Association of sedentary time and physical activity levels with immunometabolic markers in early pregnancy: The GESTAFIT project

Acosta‐Manzano

Acosta

Femia

et al. 2019

Scandinavian Med Sci Sports

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Objectives:To analyze the association of sedentary time and physical activity (PA) intensity levels with immunometabolic markers during early pregnancy; and to examine if meeting the PA recommendations is associated with the immunometabolic profile of pregnant women. Methods: Fifty Caucasian pregnant women (age: 32.8 ± 4.7 years old, body mass index: 24.2 ± 4.1kg/m 2 , gestational age: 17 ± 1.5weeks) participated in this crosssectional study (from September 2015 through May 2016). Sedentary time and PA intensity levels were objectively measured with triaxial accelerometer (seven consecutive valid days). Fasting serum glucose, total cholesterol, phospholipids, and triglycerides were assessed with standard methods. Serum pro-inflammatory and anti-inflammatory cytokines (fractalkine, interleukin-1β, interleukin-6, interleukin-8, interleukin-10, interferon-γ, and tumor necrosis factor-α) were measured using Luminex xMAP technology. Results: Sedentary time and PA were not correlated with any glycemic or lipid marker (P > .05). After adjusting for the potential confounders, vigorous PA showed a positive non-significant association with interleukin-6 (P = .06), and bouts of moderatevigorous PA was inversely associated with interleukin-1β and interferon-γ (P = .02 and P = .04, respectively). Meeting the PA guidelines was inversely associated with interleukin-1β and positively associated with interleukin-8 (P = .01 and P = .04, respectively). These associations disappeared after controlling for multiplicity. | 149ACOSTA-MANZANO eT Al. | 157ACOSTA-MANZANO eT Al.Víctor Segura-Jiménez https://orcid.

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Section: Discussionmentioning

confidence: 99%

Association of sedentary time and physical activity levels with immunometabolic markers in early pregnancy: The GESTAFIT project

Acosta‐Manzano

Acosta

Femia

et al. 2019

Scandinavian Med Sci Sports

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“…Data are presented as mean ± standard deviation, and P values less than .05 were considered statistically significant. Because this was a secondary data analysis, no adjustments for multiple comparisons were made …”

Section: Methodsmentioning

confidence: 99%

Full axillary lymph node dissection and increased breast epidermal thickness 1 year after radiation therapy for breast cancer

Lin

Yang

Serra

et al. 2019

Journal of Surgical Oncology

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Background We previously reported a prospective study showing axillary lymph node dissection (ALND) is associated with increased breast skin thickening during and 6 weeks post‐radiation therapy (RT), and now report ALND's long‐term impact at 1 year. Methods Among 66 women who received whole breast RT after lumpectomy, objective ultrasound measurements of epidermal thickness over four quadrants of the treated breast were measured at five time points: before RT, week 6 of RT, and 6 weeks, 6 months, and 1 year post‐RT. Skin thickness ratio (STRA) was generated by normalizing for corresponding measurements of the contralateral breast. Results A total of 2,436 ultrasound images were obtained. Among 63 women with evaluable data at 1 year, mean STRA significantly increased at 6 months (absolute mean increase of 65%, SD 0.054), and remained elevated at 1 year post‐RT (absolute mean increase of 44%, SD 0.048). In multivariable analysis, ALND compared to sentinel lymph node biopsy, longer interval between surgery and RT, increased baseline STRA, and Caucasian race predicted for more severe changes in STRA at 1 year compared to baseline (all P < .05). Conclusions In the setting of whole breast RT, our findings suggest that ALND has long‐term repercussions on breast skin thickening.

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“…P values were not corrected for multiple testing, as this study was of exploratory nature. [25][26][27]…”

Section: Multi-parameter Regression Modellingmentioning

confidence: 99%

Sex-associated differences in cytomegalovirus prevention: Prophylactic strategy is associated with a strong kidney function impairment in female renal transplant patients

Blázquez-Navarro

Dang-Heine

Bauer

et al. 2019

Preprint

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Post-transplantation cytomegalovirus (CMV) syndrome can be prevented using the antiviral drug (val)ganciclovir. (Val)ganciclovir is typically administered following a prophylactic or a pre-emptive strategy. The prophylactic strategy entails early universal administration, the pre-emptive strategy, early treatment in case of infection. However, it is not clear which strategy is superior with respect to transplantation outcome; sex-specific effects of these prevention strategies are not known. We have retrospectively analysed 540 patients from the multi-centre Harmony study along eight pre-defined visits: 308 were treated according to a prophylactic, 232 according to a pre-emptive strategy. As expected, we observed an association of prophylactic strategy with lower incidence of CMV syndrome, delayed onset and lower viral loads compared to the pre-emptive strategy. However, in female patients, the prophylactic strategy was associated with a strong impairment of glomerular filtration rate one year post-transplant (difference: -12.0±4.2 mL·min -1 ·1.73m -2 , P=0.005). Additionally, we observed a tendency of higher incidence of acute rejection and severe BK virus reactivation in the prophylactic strategy group. While the prophylactic strategy was more effective for preventing CMV syndrome, our results suggest for the first time that the prophylactic strategy might lead to inferior transplantation outcomes in female patients, providing evidence for a strong association with sex.

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An introduction to multiplicity issues in clinical trials: the what, why, when and how

Cited by 229 publications

References 60 publications

Association of sedentary time and physical activity levels with immunometabolic markers in early pregnancy: The GESTAFIT project

Association of sedentary time and physical activity levels with immunometabolic markers in early pregnancy: The GESTAFIT project

Full axillary lymph node dissection and increased breast epidermal thickness 1 year after radiation therapy for breast cancer

Sex-associated differences in cytomegalovirus prevention: Prophylactic strategy is associated with a strong kidney function impairment in female renal transplant patients

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