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Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
PMC9974829
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or ...
PMC9974829
References
PMC9974829
Subject terms
CORTEX
Task shielding is an important executive control demand in dual-task performance enabling the segregation of stimulus–response translation processes in each task to minimize between-task interference. Although neuroimaging studies have shown activity in left dorsolateral prefrontal cortex (dlPFC) during various multita...
PMC10105771
Introduction
CORTEX
Multitasking is required in a variety of contexts in modern life, ranging from multimedia use to vehicle operation and scheduling of complex task sequences in an emergency room. Yet, performing even two simple cognitive tasks at the same time often results in between-task interference, e.g., when the engagement in an a...
PMC10105771
Methods
PMC10105771
Participants
thirty-four
Forty-one participants signed up for participation in the experiment. Data sets of seven participants were not usable for analyses because of technical problems during recording (one participant), not completing both sessions (four participants), difficulties following task instructions, and obvious signs of disinteres...
PMC10105771
Study overview
The study was conducted as a single-blind, crossover, sham-controlled trial. Each participant completed two sessions on separate days, with an average of 7 days between the two sessions. They received either atDCS or sham tDCS with the order of stimulation conditions being counterbalanced, i.e., half of the participant...
PMC10105771
Materials and methods
PMC10105771
Behavioral task
The dual task consisted of a visual discrimination task (Task 1) and an auditory discrimination task (Task 2), which were performed in close succession. In order to increase processing similarities between the two tasks as the basis for crosstalkStimuli were presented in Arial font (font size 30) and in white on a blac...
PMC10105771
Stimulation protocol
SimNibs
Stimulation was delivered (NeuroConn DCStimulator Plus; neuroCare Grouo GmbH, Munich, Germany) using two saline-soaked surface sponge electrodes over the left dlPFC (anode, centered over F3, 10–20 EEG system, size: 5 × 7 cmDemonstration of the electrode placement and simulation of electric field distribution of applied...
PMC10105771
Design
A 2 (Stimulation condition: atDCS, sham tDCS) × 2 (Compatibility: compatible, incompatible) × 3 (SOA: 40, 130, 300 ms) repeated measures single-blind, crossover, sham-controlled design was applied. Because BCEs take effect in Task 1 performance
PMC10105771
Analysis
The practice block of each session was not considered for analyses. Before RT analyses, erroneous trials in either Task 1 or Task 2 were removed. Further, all trials with RT1 < 200 ms and RT1 > 2000 ms and RT2 < 200 ms, and RT2 > 2500 ms were considered outliers and were not included in the analysis. This led to a remo...
PMC10105771
Results
PMC10105771
PE1
Participants made more errors in Task 1 when the Task 2 response was incompatible (Importantly, the application of atDCS modulated the BCE as compared to sham tDCS across the three SOAs, as indicated by the significant three-way interaction between Stimulation condition, SOA, and Compatibility, To test for potential ef...
PMC10105771
RT1
Participants responded faster in compatible trials (There was also a significant main effect of SOA,
PMC10105771
PE2
Mean PE2 is summarized in Table
PMC10105771
RT2
Mean correct RT2 is summarized in Table
PMC10105771
General tDCS effects
itching, fatigue, pain
HEAT, SIDE EFFECT
The frequency and severity of reported side effects (i.e., itching, pain, burning, heat, metallic taste, and fatigue) were assessed for the last experimental session. None of the participants reported metallic taste as a side effect in atDCS or sham tDCS. Two-sided Fisher exact tests revealed no association between the...
PMC10105771
Discussion
The present study investigated whether modulation of excitability in the left-lateralized executive control network, as modulated by a prefrontal tDCS setup with anode over left dlPFC, facilitated the executive control function of prioritized task shielding in dual tasking. Results demonstrated that atDCS, as compared ...
PMC10105771
Limitations
The present study used a conventional tDCS setup as applied in previous studies that reported successful tDCS-related dual-task performance benefitsIn addition, to potentially increase blinding efficacy, a double-blind design might be taken into consideration. We carefully implemented certain protocols to standardize t...
PMC10105771
Acknowledgements
We thank Josefin Fruck and Hannah Pünjer for their assistance in data collection.
PMC10105771
Author contributions
D.M., D.A., R.F. conceived and designed the experiment, D.M. analyzed the data under the supervision of R.F., D.M. and R.F. wrote the manuscript, D.A. and A.F. edited, and revised the manuscript. D.M. prepared Figs. 
PMC10105771
Funding
Open Access funding enabled and organized by Projekt DEAL.
PMC10105771
Data availability
The datasets generated during the current study are available in the PsychArchives repository, 10.23668/psycharchives.8155.
PMC10105771
Competing interests
The authors declare no competing interests.
PMC10105771
References
PMC10105771
Background
Rates of advance directive (AD) completion in the United Kingdom are lower than in the United States and other western European countries, which is especially concerning in light of the COVID-19 pandemic. UK residents typically complete an advance decision to refuse care (ADRT), whereas US versions of ADs present a mor...
PMC10196681
Methods
In an online experiment, 801 UK-based respondents were randomly allocated to document their preferences for end-of-life care in a 2 (US AD or UK ADRT) by 2 (presence or absence of COVID-19 prime) between-subjects factorial design.
PMC10196681
Results
Most (74.8%) of participants across all conditions chose comfort-oriented care. However, framing comfort care as a refusal of treatment made respondents significantly less likely to choose it (65.4% v. 84.1%,
PMC10196681
Conclusions
The UK ADRT significantly reduced the proportion of participants choosing comfort-oriented care, an effect that was heightened in the presence of information about COVID-19. This suggests the current way end-of-life care wishes are documented in the United Kingdom could affect people’s choices in a way that does not al...
PMC10196681
Highlights
deaths, death, infections, infectious disease
INFECTIOUS DISEASE, VIRUS, INFECTIONS
Participants completing an AD framed as an advance decision to refuse treatment were significantly less likely to choose comfort-oriented care than participants completing an AD with a neutral choice between comfort-oriented and life-prolonging care.Exposure to a COVID-19 prime had an interactive effect on documented p...
PMC10196681
Methods
EVENT
A preregistered online randomized experiment was conducted in which participants documented their preferences for end-of-life care, in the event of being unable to communicate their wishes (
PMC10196681
UK condition
PMC10196681
US condition
Following completion of the form, participants were asked additional questions about attitudes toward and experiences of health care, their concerns and experiences with COVID-19, and demographic information such as age, sex, education, and ethnicity.
PMC10196681
Outcomes
death, dementia
CORONAVIRUS, DISEASE, SECONDARY
The primary outcome is whether participants choose comfort care or life-prolonging care, in 3 domains: 1) as the overall preference for their care, 2) in the case of 4 specific illnesses (being diagnosed with dementia, a brain injury, a disease of the CNS, and other terminal illnesses), and 3) in the case of 5 specific...
PMC10196681
Power Calculation
REGRESSION
The necessary sample size to detect a minimum effect size of 0.3 (a small to medium minimum effect size), with 0.80 power and a standard 0.05 alpha error probability, was calculated using G*Power for a Wilcoxon-Mann-Whitney nonparametric test and a logistic regression. The sample size per group was between 160 and 184,...
PMC10196681
Statistical Analyses
REGRESSIONS
Data were analysed using Wilcoxon-Mann-Whitney nonparametric tests for differences-in-proportions. Further analysis was performed using logistic regressions to determine the main effects of country frame and prime, their interactive effects, and control for additional variables such as age, gender, and ethnicity. To ac...
PMC10196681
Results
PMC10196681
Participants
A total of 801 UK resident participants were recruited through Prolific Academic, of whom 60.6% were female, with an average age of 34.08 ± 13.1 y (ranging from 18 to 80 y). Ethnicity was predominantly White at 84.1%, 8.5% Asian, 2.5% Black, 3.9% mixed race, and 1% other. Participant Characteristics by Experimental Con...
PMC10196681
Exploratory Analysis for Overall Goal of Care
REGRESSION, REGRESSIONS
The logistic regressions with control variables also highlighted further findings for which explicit hypotheses were not included in the preregistration. In particular, older respondents, respondents for whom religion was important, or respondents who were very worried about COVID-19 were more likely to choose comfort ...
PMC10196681
Correlations between Choices
Decisions for the overall goal of care, specific illnesses, and specific medical treatments were all highly correlated. Between specific illnesses, these ranged from
PMC10196681
Documenting End-of-Life Decisions
The self-reported likelihood of formally documenting end-of-life preferences in the near future did not significantly differ across conditions. In the US condition, 35.8% of participants stated they were likely or very likely to do so, compared with 36.6% in the UK condition (z = 1.33, For the behavioral measure, only ...
PMC10196681
Discussion
cancer, AD
CANCER, VIRUS
This study is the first of its kind to experimentally examine the difference between a US-style AD, in which the choice between comfort and life-prolonging care is presented neutrally, and the ADRT used in the United Kingdom, where comfort care is framed as refusing treatment. This was combined with a COVID-19 prime, t...
PMC10196681
Conclusions
This study is the first of its kind to experimentally examine the effect of framing comfort care as a refusal of treatment on people’s choices between comfort or life-prolonging care. While the majority of participants still chose comfort care and personal preferences played a role, this framing made people significant...
PMC10196681
Supplemental Material
PMC10196681
References
PMC10196681
Supplementary Information
ICH, FIP
FIP
The first-in-patient (FIP) starting dose for oncology agents should be reasonably safe and provide potential therapeutic benefit to the patient. For late-stage oncology patients, this dose is often based on the ICH S9 guidance, which was developed primarily based on experience with cytotoxic chemotherapeutic agents usi...
PMC10638197
Keywords
PMC10638197
Introduction
cancer, FIP, ICH
MALIGNANCIES, CANCER, FIP
The first-in-patient (FIP) nonclinical safety package is designed to enable an initial risk assessment of the drug candidate, identify appropriate clinical safety monitoring, and define the recommended starting dose (RSD) for the FIP clinical trial. The FIP trial for oncology agents is generally conducted in patients w...
PMC10638197
Methods
dose-limiting, toxicities, FIP
STD, FIP
An IQ DruSafe Working Group was formed to evaluate an alternative approach to setting starting doses in oncology FIP clinical studies. The scope was small molecule marketed MTA oncology drugs or those in clinical development that had reached an MTD/RP2D. A database was created capturing 50 fields of information for eac...
PMC10638197
Results
PMC10638197
Overview
ICH
The companies were asked to characterize the target class for the compound (Table Target class*Other (With regard to the MTA nonclinical toxicology FIP-enabling packages, 74% were conducted after the implementation of ICH S9. The dosing route was oral in 86% of cases for both nonclinical and clinical studies. The major...
PMC10638197
Analysis of nonclinical NOAEL
toxicity, ICH
SECONDARY
The determination of a NOAEL in toxicology studies conducted to support the clinical dosing of new drugs to oncology patients is not a required endpoint in ICH S9 [When assessing criteria for justifying the starting dose in clinical studies, it is important to understand species sensitivity to the compound with the mor...
PMC10638197
Discussion
NOAEL-based, toxicity, cancer, toxicities, ICH, FIP
CANCER, FIP
The primary goal of selecting a FIP starting dose for cancer patients should be to define a safe dose level that is sufficiently high to potentially result in clinical benefit and to enable rapid identification of the RP2D [Similarly, Le Tourneau et al. reviewed the Scopus abstract database for FIP trials of MTAs in ca...
PMC10638197
Acknowledgements
The database was developed under the auspices of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), a not-for-profit organization of pharmaceutical and biotechnology companies with a mission of advancing science and technology to augment the capability of member companies to dev...
PMC10638197
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
PMC10638197
Declarations
PMC10638197
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
PMC10638197
References
PMC10638197
Purpose:
mRCC, P., Cancer
METASTATIC RENAL CELL CARCINOMA, CANCER
Current address for P. Iruku: Cone Health Cancer Center, Greensboro, North Carolina; and current address for M. Amirault, Massachusetts General Hospital, Boston, Massachusetts. Immune checkpoint inhibitor and VEGFR inhibitor combinations are effective treatments for patients with metastatic renal cell carcinoma (mRCC)....
PMC10249509
Experimental Design:
non-clear, clear-cell
ONCOLOGY, DISEASE
Eligible patients had mRCC with clear-cell or non-clear cell histology, adequate organ function, Eastern Cooperative Oncology Group 0–1 performance status, and no prior exposure to pembrolizumab or cabozantinib. The primary endpoint was objective response rate (ORR) at the recommended phase II dose (RP2D). Secondary en...
PMC10249509
Results:
nausea, diarrhea, fatigue, encephalopathy, dysgeusia, weight loss, anorexia
HYPOPHOSPHATEMIA, ADVERSE EVENTS, ENCEPHALOPATHY, SYNDROME, HYPERTENSION, ANOREXIA
Forty-five patients were enrolled. A total of 40 patients were treated at the RP2D of pembrolizumab 200 mg i.v. every 3 weeks and cabozantinib 60 mg orally once daily, 38 of which were evaluable for response. The ORR was 65.8% [95% confidence interval (CI), 49.9–78.8] for all evaluable patients [78.6% as first-line the...
PMC10249509
Conclusions:
toxicity
Pembrolizumab and cabozantinib treatment in patients with mRCC demonstrated encouraging preliminary efficacy and a manageable toxicity profile comparable with other available checkpoint inhibitor-tyrosine kinase inhibitor combinations.
PMC10249509
Trial Registration:
ClinicalTrials.gov Identifier: NCT03149822
PMC10249509
Significance:
This study evaluated the safety and effectiveness of the combination of pembrolizumab and cabozantinib in patients with mRCC. The safety profile was manageable. The combination showed promising activity with an objective response rate of 65.8%, median PFS of 10.45 months, and median OS of 30.81 months.
PMC10249509
Introduction
Kidney cancer, cancer
KIDNEY CANCER, DISEASE, CANCER
Kidney cancer is an important cancer worldwide with an estimated 431,000 new cases globally and 81,800 new cases in the United States with a 5-year survival of 13% for stage IV disease (Pembrolizumab, a potent and highly selective humanized monoclonal anti-PD-1 antibody, has demonstrated survival benefit in combination...
PMC10249509
Materials and Methods
PMC10249509
Patient Eligibility
pneumonitis, RPLS, toxicities, clear-cell RCC, non-clear, RCC, autoimmune disease
ADVERSE EVENT, PNEUMONITIS, IMMUNODEFICIENCY, REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME, WOUND DEHISCENCE, ONCOLOGY, OSTEONECROSIS OF THE JAW, AUTOIMMUNE DISEASE, RCC
Eligible patients had histologically confirmed, locally advanced, recurrent, or mRCC. Patients with clear-cell RCC (ccRCC) or non-clear cell RCC (nccRCC) were included. Key inclusion criteria were Eastern Cooperative Oncology Group 0–1 performance status, adequate organ function, and resolution of prior treatment-relat...
PMC10249509
Study Design and Treatment
Phase I dose escalation was done using a standard 3 + 3 design. Phase II dose expansion was done using a Simon two-stage design (The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines. The protocol was approved by the Institutional Review Board and all patients prov...
PMC10249509
Study Endpoints
toxicities, tumor, DLT
DISEASE, BONE METASTASES, TUMOR
The primary endpoint of the overall study was objective response rate (ORR) in patients treated at the RP2D of pembrolizumab and cabozantinib. Secondary endpoints included dose-limiting toxicities (DLT), MTD, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of treatment, time...
PMC10249509
Antitumor Activity Assessments
Tumor
TUMOR
Tumor assessments were performed at baseline and every 9 weeks on study. Tumor responses were evaluated based on investigator assessment per RECIST 1.1 (
PMC10249509
Safety Assessments
DLT was defined as any treatment-related AE (TRAE) grade 3 or higher that occurred during the 21-day DLT assessment window. Any dose-escalation patient who did not complete the DLT period for any reason other than a DLT was replaced by an additional patient at that same dose level. DLT-evaluable patients were required ...
PMC10249509
Exploratory Assessments
tumor
TUMOR
PD-L1 testing was performed on archival tumor tissues by Discovery Life Sciences (formerly QualTek Molecular Laboratories) using a previously validated IHC assay for PD-L1 using the Merck & Co., Inc proprietary mouse mAb clone 22C3 for the testing of formalin-fixed, paraffin-embedded tissues (
PMC10249509
Statistical Analysis
PD, death
DISEASE
The planned enrollment was estimated to be 6–9 evaluable patients in phase I and 20–38 evaluable patients in phase II. For the primary endpoint of ORR, a Simon two-stage design was used to test the null hypothesis that ORR ≤ 0.20 versus the alternative that ORR ≥ 0.50. After enrollment of 20 evaluable patients in the f...
PMC10249509
Data Availability Statement
Source data generated in this study are not publicly available due to compromise of patient privacy. Derived data supporting the findings of this study may be available from the corresponding author upon request.
PMC10249509
Results
PMC10249509
Patients
toxicity
ONCOLOGY, RCC
Between October 2017 and August 2020, 45 patients were enrolled (8 patients in phase I and 37 patients in phase II) across five sites within the University of Colorado/UCHealth system. A total of 40 patients were treated at the RP2D and were evaluable for PFS and OS, and 38 patients were evaluable for response (CONSORT...
PMC10249509
MTD and DLT Evaluation
Eight patients were enrolled in phase I [5 patients in the first cohort of pembrolizumab 200 mg and cabozantinib 40 mg (2 were not evaluable for DLT due to missing ≥25% of the planned cabozantinib doses in cycle 1, not related to TRAE) and 3 patients in the second cohort of pembrolizumab 200 mg and cabozantinib 60 mg]....
PMC10249509
Safety
RPLS
REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME, ADVERSE EVENT
The most common TRAEs in all 45 patients are reported in TRAEs in ≥10% of patients and all grade ≥3Abbreviations: AE, adverse event; ALT, alanine transaminase; AST, aspartate transaminase; No., number of patients; RPLS, reversible posterior leukoencephalopathy syndrome.
PMC10249509
Efficacy
PD, tumor, clear-cell renal cell carcinoma, non-clear cell renal cell carcinoma
EVENTS, TUMOR, BEST
Thirty-eight patients were evaluable for tumor response at the RP2D (pembrolizumab 200 mg i.v. every 3 weeks and cabozantinib 60 mg orally daily). The ORR was 65.8% (25/38 patients, 95% CI, 49.9–78.8) with 1 CR, 24 PR, 12 SD, 1 PD. The ORR was 78.6% (11/14) in evaluable patients who received study treatment as 1 L ther...
PMC10249509
Exploratory Studies
PD, tumor, MPS
TUMOR, BONE METASTASES
There were 44 samples of archival tissue available for PD-L1 testing, 40 of which (90.9%) were interpretable and four samples which did not have tumor in the specimen. Of the 40 evaluable samples, 32 (80.0%) had PD-L1 tumor MPS ≥ 1. The ORR was 69% in patients with PD-L1–positive samples and 50% in patients with PD-L1–...
PMC10249509
Discussion
tumor, RCC
TUMOR, BONE METASTASES, RCC
We conducted this phase I/II study of pembrolizumab and cabozantinib beginning in 2017, prior to the FDA approvals of combination CPI-TKI therapies including pembrolizumab and axitinib in 2019, and nivolumab and cabozantinib and pembrolizumab and lenvatinib in 2021. In our study, the primary endpoint of ORR for all pat...
PMC10249509
Limitations
tumors
TUMORS
Inherent to small phase I/II studies, the main limitations of this clinical trial include small number of patients, single-arm design with no comparator treatment arm, and absence of randomization. Another limitation is the heterogeneity of the patients included in this study. Because of demonstrated activity of caboza...
PMC10249509
Conclusions
toxicity
The combination of pembrolizumab and cabozantinib treatment in patients with mRCC demonstrated encouraging preliminary efficacy that is comparable with other available CPI-TKI combinations with a manageable toxicity profile. Further prospective evaluation of pembrolizumab and cabozantinib is warranted, especially in th...
PMC10249509
Supplementary Material
clear cell renal cell carcinoma
CLEAR CELL RENAL CELL CARCINOMA, EVALUABLE, BEST
Supplemental Figure S1: Kaplan-Meier curves of (A) progression-free survival (PFS) and (B) overall survival (OS) for patients with clear cell renal cell carcinoma histology (N=34). Vertical lines show censored patientsClick here for additional data file.Best Response by RECIST in Evaluable Patients Treated at RP2D (Pem...
PMC10249509
Acknowledgments
Cancer
ONCOLOGY, CANCER
We are grateful to the patients who participated in this study, their caretakers, and families. In addition, we thank the study coordinators, nurses, and pharmacy teams at all the study sites, the University of Colorado Cancer Center Cancer Clinical Trials Office, and Oncology Clinical Research Support Team.
PMC10249509
Authors’ Disclosures
OnQuality, Cancer
ONCOLOGY, CANCER, MOORE
E.R. Kessler reports grants from Merck during the conduct of the study; grants from Bristol Myers Squibb, Seattle Genetics, Eli Lily, and AstraZeneca outside the submitted work. J. Moore reports other from Merck outside the submitted work. T.W. Flaig reports other from MERCK and Exelixis during the conduct of the study...
PMC10249509
Role of the Funder/Sponsor
Cancer
CANCER
This was an investigator-initiated study coordinated by the University of Colorado Cancer Center (sponsor) and E.T. Lam (principal investigator) who were responsible for administering the study and coordinating the subsites involved in the study. The funder did not have a role in the design and conduct of the study; co...
PMC10249509
Authors’ Contributions
PMC10249509
References
PMC10249509
Background
death
DISEASE PROGRESSION, COVID-19 INFECTION
The COMET-ICE trial demonstrated that sotrovimab clinically and statistically significantly reduces the risk of all-cause > 24-h hospitalization or death due to any cause among patients with COVID-19 at high risk of disease progression. Patient-reported outcomes are important to capture symptom burden of COVID-19 and a...
PMC10499766
Methods
obesity, asthma, chronic kidney disease, diabetes
OBESITY, DISEASE PROGRESSION, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, CONGESTIVE HEART FAILURE, ASTHMA, DIABETES
Randomized (1:1), double-blind, multicenter, placebo-controlled, phase 2/3 study in 57 centers across five countries. Participants were non-hospitalized patients with symptomatic, mild-to-moderate COVID-19 and ≥ 1 baseline risk factor for disease progression (aged ≥ 55 years or ≥ 1 of the following: diabetes requiring ...
PMC10499766
Results
In total, 1057 patients were randomized to sotrovimab (n = 528) or placebo (n = 529). At Day 7, mean decrease in FLU-PRO Plus total score (measured by AUC) was statistically significantly greater for patients on sotrovimab (–3.05 [95% confidence interval (CI) –3.27 to –2.83]) than placebo (–1.98 [95% CI –2.20 to –1.76]...
PMC10499766
Supplementary Information
The online version contains supplementary material available at 10.1186/s41687-023-00621-8.
PMC10499766
Keywords
PMC10499766
Introduction
SARS
SEVERE ACUTE RESPIRATORY SYNDROME
Sotrovimab is an Fc-engineered pan-sarbecovirus human monoclonal antibody, which was developed for the treatment of COVID-19 from a parental antibody isolated from a survivor of the severe acute respiratory syndrome (SARS) outbreak in 2003 [The Globally, COVID-19 is associated with significant clinical, public health a...
PMC10499766
Methods
COMET-ICE was a randomized, double-blind, multicenter, placebo-controlled phase 2/3 study, involving 57 centers across five countries (CONSORT-PRO checklist available in Additional file The COMET-ICE study was conducted in accordance with the principles of the Declaration of Helsinki and Council for International Organ...
PMC10499766
PRO measurements
fatigue, throat, cough, gastrointestinal, body/systemic, and sense., taste and smell assessments, loss of smell or taste
DISEASE
Questionnaires were administered using an electronic device where possible. A paper PRO option was used in instances where logistical or technical difficulties in using electronic PROs were experienced. FLU-PRO Plus was completed once-daily with a 24-h recall, from Day 1 through Day 21, and then at Day 29, Week 8, and ...
PMC10499766
Statistical analysis
SECONDARY
Change in FLU-PRO Plus total score (AUC) through Day 7 was a secondary trial endpoint, formally tested with an alpha level of 5% (two-sided) after adjustment for multiplicity using a pre-specified testing hierarchy (Fig. S1 in Additional file Subgroup analyses by symptom severity were adjusted for treatment, baseline v...
PMC10499766