Comparison of HIV incidence estimated in clinical trial and observational cohort settings in a high risk fishing population in Uganda: Implications for sample size estimates

e22091 Background: Deaths due to cSCC are expected to exceed melanoma-specific deaths. With the demonstration of effective therapies for advanced cSCC, and as treatment of patients in the adjuvant setting is considered, accurate prognosis is critical. For improved identification of ‘high-risk’ patients, with biologically aggressive disease capable of metastasis, a prognostic 40-gene expression profile (40-GEP) test was validated using an independent cohort of patients with high-risk cSCC and known clinical outcomes. The test identified three groups with increasing metastasis risk profiles: Class 1 (low risk), Class 2A (high risk), and Class 2B (highest risk) having metastasis rates of 8.9%, 20.4%, and 60%, respectively. Multivariable analysis demonstrated prognostic efficacy of the 40-GEP test alone and in combination with clinicopathological staging systems. This study evaluated risk stratification with concurrent consideration of the 40-GEP result and the Brigham and Women’s Hospital (BWH) stage. The primary objective was evaluation of the potential impact of the 40-GEP on adjuvant clinical trial design. Methods: To determine if a 40-GEP Class 2B result could optimize clinical trial accrual, metastasis rates of BWH high-risk T stage patients (T2b-T3) alone and in combination with 40-GEP results from the validation cohort were used for two-arm trial sample size calculations. Results: Metastasis rates for cases with T2b-T3 tumors increased from 35.1% to 71.4% when selecting for T2b-T3 cases with a 40-GEP Class 2B result. To provide 80% power to detect hazard ratio of 0.6 with 3 years of follow-up (alpha = 0.05), in line with improvement rates by addition of radiation to surgery, 434 T2b-T3 patients are required for randomization. However, sample size could be reduced by 51% to 214 patients by focusing enrollment on T2b-T3 patients with a 40-GEP Class 2B result. Conclusions: These results support the incorporation of the 40-GEP test into selection processes for patients with T2b-T3 tumors who are at the highest risk for metastasis and appropriate for adjuvant clinical trials.

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Abstract #2: Diffusion Tensor Imaging As a Neuroprotection Outcome Metric in Multiple Sclerosis: Clinical Trial Sample Size Estimates

Neurotherapeutics ◽

10.1016/j.nurt.2010.06.004 ◽

2010 ◽

Vol 7 (3) ◽

pp. 328-328

Author(s):

Robert J. Fox ◽

Thomas Cronin ◽

Jian Lin ◽

Ken Sakaie ◽

Daniel Ontaneda ◽

...

Keyword(s):

Multiple Sclerosis ◽

Clinical Trial ◽

Diffusion Tensor Imaging ◽

Sample Size ◽

Diffusion Tensor ◽

Size Estimates

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Honey and Nigella Sativa in the Prophylaxis of COVID-19; A Randomized Controlled Trial

10.21203/rs.3.rs-757643/v1 ◽

2021 ◽

Author(s):

Sohaib Ashraf ◽

Shoaib Ashraf ◽

Rutaba Akmal ◽

Moneeb Ashraf ◽

Larab Kalsoom ◽

...

Keyword(s):

Clinical Trial ◽

High Risk ◽

Sample Size ◽

Nigella Sativa ◽

Risk Exposure ◽

Medical Institute ◽

Care Providers ◽

Post Graduate ◽

Graduate Medical ◽

Allocation Ratio

Abstract ObjectivesConsidering the therapeutic potential of honey and Nigella sativa (HNS) in coronavirus disease 2019 (COVID-19) patients, the objective of the study is defined to evaluate the prophylactic role of HNS. Trial designThe study is a randomized, placebo-controlled, adaptive clinical trial with parallel group design, superiority framework with an allocation ratio of 1:1 among experimental (HNS) and placebo group. An interim analysis will be done when half of the patients have been recruited to evaluate the need to adapt sample size, efficacy, and futility of the trial.ParticipantsAll asymptomatic patients with hospital or community based COVID-19 exposure will be screened if they have had 4 days exposure to a confirmed case. Non-pregnant adults with significant exposure level will be enrolled in the study● High-risk exposure (<6 feet distance for >10min without face protection) ● Moderate exposure (<6 feet distance for >10min with face protection)Subjects with acute or chronic infection, COVID-19 vaccinated, and allergy to HNS will be excluded from the study.Recruitment will be done at Shaikh Zayed Post-Graduate Medical Institute, Ali Clinic and Doctors Lounge in Lahore (Pakistan). Intervention and comparatorIn this clinical study, patients will receive either raw natural honey (0.5 g) and encapsulated organic Nigella sativa seeds (40 mg) per kg body weight per day or empty capsule with and 30 ml of 5% dextrose water as a placebo for 14 days. Both the natural products will be certified for standardization by Government College University (Botany department). Furthermore, each patient will be given standard care therapy according to version 3.0 of the COVID-19 clinical management guidelines by the Ministry of National Health Services of Pakistan.Main outcomesPrimary outcome will be Incidence of COVID-19 cases within 14 days of randomisation. Secondary endpoints include incidence of COVID-19-related symptoms, hospitalizations, and deaths along with the severity of COVID-19-related symptoms till 14th day of randomization. RandomisationParticipants will be randomized into experimental and control groups (1:1 allocation ratio) via the lottery method. There will be stratification based on high risk and moderate risk exposure. Blinding (masking)Quadruple blinding will be ensured for the participants, care providers and outcome accessors. Data analysts will also be blinded to avoid conflict of interest. Site principal investigator will be responsible for ensuring masking.Numbers to be randomised (sample size)1000 participants will be enrolled in the study with 1:1 allocation.Trial StatusThe final protocol version 1.4 was approved by institutional review board of Shaikh Zayed Post-Graduate Medical Complex on February 15, 2021. The trial recruitment was started on March 05, 2021, with a trial completion date of February 15, 2022. Trial registrationClinical trial was registered on February 23, 2021, www.clinicaltrials.gov with registration ID NCT04767087.

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Prophylactic potential of honey and Nigella sativa L. against hospital and community-based SARS-CoV-2 spread: a structured summary of a study protocol for a randomised controlled trial

Trials ◽

10.1186/s13063-021-05510-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Sohaib Ashraf ◽

Shoaib Ashraf ◽

Rutaba Akmal ◽

Moneeb Ashraf ◽

Larab Kalsoom ◽

...

Keyword(s):

Clinical Trial ◽

High Risk ◽

Sample Size ◽

Study Protocol ◽

Nigella Sativa ◽

Risk Exposure ◽

Community Based ◽

Post Graduate ◽

Full Protocol ◽

Allocation Ratio

Abstract Objectives Considering the therapeutic potential of honey and Nigella sativa (HNS) in coronavirus disease 2019 (COVID-19) patients, the objective of the study is defined to evaluate the prophylactic role of HNS. Trial design The study is a randomized, placebo-controlled, adaptive clinical trial with parallel group design, superiority framework with an allocation ratio of 1:1 among experimental (HNS) and placebo group. An interim analysis will be done when half of the patients have been recruited to evaluate the need to adapt sample size, efficacy, and futility of the trial. Participants All asymptomatic patients with hospital or community based COVID-19 exposure will be screened if they have had 4 days exposure to a confirmed case. Non-pregnant adults with significant exposure level will be enrolled in the study High-risk exposure (<6 feet distance for >10min without face protection) Moderate exposure (<6 feet distance for >10min with face protection) Subjects with acute or chronic infection, COVID-19 vaccinated, and allergy to HNS will be excluded from the study. Recruitment will be done at Shaikh Zayed Post-Graduate Medical Institute, Ali Clinic and Doctors Lounge in Lahore (Pakistan). Intervention and comparator In this clinical study, patients will receive either raw natural honey (0.5 g) and encapsulated organic Nigella sativa seeds (40 mg) per kg body weight per day or empty capsule with and 30 ml of 5% dextrose water as a placebo for 14 days. Both the natural products will be certified for standardization by Government College University (Botany department). Furthermore, each patient will be given standard care therapy according to version 3.0 of the COVID-19 clinical management guidelines by the Ministry of National Health Services of Pakistan. Main outcomes Primary outcome will be Incidence of COVID-19 cases within 14 days of randomisation. Secondary endpoints include incidence of COVID-19-related symptoms, hospitalizations, and deaths along with the severity of COVID-19-related symptoms till 14th day of randomization. Randomisation Participants will be randomized into experimental and control groups (1:1 allocation ratio) via the lottery method. There will be stratification based on high risk and moderate risk exposure. Blinding (masking) Quadruple blinding will be ensured for the participants, care providers and outcome accessors. Data analysts will also be blinded to avoid conflict of interest. Site principal investigator will be responsible for ensuring masking. Numbers to be randomised (sample size) 1000 participants will be enrolled in the study with 1:1 allocation. Trial Status The final protocol version 1.4 was approved by institutional review board of Shaikh Zayed Post-Graduate Medical Complex on February 15, 2021. The trial recruitment was started on March 05, 2021, with a trial completion date of February 15, 2022. Trial registration Clinical trial was registered on February 23, 2021, www.clinicaltrials.gov with registration ID NCT04767087. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). With the intention of expediting dissemination of this trial, the conventional formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

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Competing event risk stratification may improve the design and efficiency of clinical trials: Secondary analysis of SWOG 8794.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.6121 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 6121-6121

Author(s):

Brent Shane Rose ◽

Kaveh Zakeri ◽

Sachin Gulaya ◽

Anthony Victor D'Amico ◽

Loren K. Mell

Keyword(s):

Clinical Trials ◽

High Risk ◽

Sample Size ◽

Risk Score ◽

Performance Status ◽

Risk Scores ◽

Adjuvant Radiation ◽

Type I ◽

Event Risk ◽

Size Estimates

6121 Background: Efficiency of clinical trials may be improved by stratifying according to competing event risk. We aimed to test whether effect and sample size estimates would be altered when adjusting for competing event risk, using data from the SWOG 8794 trial of adjuvant radiation therapy (RT) for high-risk post-operative prostate cancer. Methods: The primary outcome was metastasis-free survival (MFS), defined as time to first occurrence of metastasis or death from any cause (i.e., competing mortality (CM)). We developed separate risk scores for time to metastasis and CM using backward stepwise competing risks regression. Risk factors for metastasis were PSA, Gleason score, and seminal vesicle invasion, and for CM were age, performance status, and Charlson comorbidity index. Treatment effects were estimated using Cox models adjusted for risk scores. We identified an enriched subgroup of 75 patients at high risk of metastasis and low risk of CM, based on risk score cutoffs. Sample size estimates assumed type I and II error of 0.10 and 0.20, and accrual and follow-up times of 6 and 6 years. Results: The mean CM risk score was significantly lower in the RT vs. control arm (p=0.001). The effect of RT on MFS (HR 0.70; 95% CI, 0.53-0.92; p=0.010) was attenuated when controlling for metastasis and CM risk (HR 0.76; 95% CI, 0.58-1.00; p=0.049). The hazard for CM was reduced by RT (HR 0.82; 95% CI, 0.59-1.14; p=0.24), but this effect was attenuated when controlling for CM risk (HR 0.94; 95% CI, 0.67-1.31; p=0.71). In contrast, there was no difference in the adjusted and unadjusted HRs for metastasis (0.50; 95% CI, 0.31-0.81; p=0.005 and 0.49; 95% CI, 0.30-0.81; p=0.005). Compared to the whole cohort, the enriched subgroup had the same baseline 10-year incidence of MFS (40%; 95% CI 22-57%), but a higher incidence of metastasis (30% (95% CI, 15-47%) vs. 20% (95% CI, 15-26%)). A randomized trial in an enriched population could have achieved 80% power with 44% less patients (313 vs. 709 patients, respectively), due to the differing event composition. Conclusions: Stratification based on competing event risk may improve the design and efficiency of clinical trials. These findings should be externally validated.

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Featured Clinical Trial: Study of Individuals and Families at High Risk for Blood Cancers

PsycEXTRA Dataset ◽

10.1037/e301012005-006 ◽

2004 ◽

Author(s):

Keyword(s):

Clinical Trial ◽

High Risk

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Featured Clinical Trial: Study of Individuals and Families at High Risk for Melanoma

PsycEXTRA Dataset ◽

10.1037/e306192005-010 ◽

2004 ◽

Author(s):

Keyword(s):

Clinical Trial ◽

High Risk

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Planning the Size of Clinical Trials with Allowance for Patient Noncompliance

Methods of Information in Medicine ◽

10.1055/s-0038-1634787 ◽

1990 ◽

Vol 29 (03) ◽

pp. 243-246 ◽

Cited By ~ 2

Author(s):

M. A. A. Moussa

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Sample Size ◽

Event Rate ◽

Survival Functions ◽

Time Intervals ◽

Patient Noncompliance ◽

Event Rates ◽

Larger Sample

AbstractVarious approaches are considered for adjustment of clinical trial size for patient noncompliance. Such approaches either model the effect of noncompliance through comparison of two survival distributions or two simple proportions. Models that allow for variation of noncompliance and event rates between time intervals are also considered. The approach that models the noncompliance adjustment on the basis of survival functions is conservative and hence requires larger sample size. The model to be selected for noncompliance adjustment depends upon available estimates of noncompliance and event rate patterns.

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