19 research outputs found
Multi-institution analysis of racial disparity among African- American men eligible for prostate cancer active surveillance
There is a significant controversy on whether race should be a factor in considering active surveillance for low-risk prostate cancer. To address this question, we analyzed a multi-institution database to assess racial disparity between African-American and White-American men with low risk prostate cancer who were eligible for active surveillance but underwent radical prostatectomy. A retrospective analysis of prospectively collected clinical, pathologic and oncologic outcomes of men with low-risk prostate cancer from seven tertiary care institutions that underwent radical prostatectomy from 2003–2014 were used to assess potential racial disparity. Of the 333 (14.8%) African-American and 1923 (85.2%) White-American men meeting active surveillance criteria, African-American men were found to be slightly younger (57.5 vs 58.5 years old; p = 0.01) and have higher BMI (29.3 v 27.9; p \u3c 0.01), pre-op PSA (5.2 v 4.7; p \u3c 0.01), and maximum percentage cancer on biopsy (15.1% v 13.6%; p \u3c 0.01) compared to White-American men. Univariate and multivariate analysis demonstrated similar rates of upgrading, upstaging, positive surgical margin, and biochemical recurrence between races. These results suggest that single institution studies recommending more stringent AS enrollment criteria for AA men with a low-risk prostate cancer may not capture the complete oncologic landscape due to institutional variability in cancer outcomes. Since all seven institutions demonstrated no significant racial disparity, current active surveillance eligibility should not be modified based upon race until a prospective study has been completed. © Dinizo et al
Problems in dealing with missing data and informative censoring in clinical trials
A common problem in clinical trials is the missing data that occurs when patients do not complete the study and drop out without further measurements. Missing data cause the usual statistical analysis of complete or all available data to be subject to bias. There are no universally applicable methods for handling missing data. We recommend the following: (1) Report reasons for dropouts and proportions for each treatment group; (2) Conduct sensitivity analyses to encompass different scenarios of assumptions and discuss consistency or discrepancy among them; (3) Pay attention to minimize the chance of dropouts at the design stage and during trial monitoring; (4) Collect post-dropout data on the primary endpoints, if at all possible; and (5) Consider the dropout event itself an important endpoint in studies with many
Kidney outcomes using a sustained ≥40% decline in eGFR: A meta-analysis of SGLT2 inhibitor trials
Background: A recent meta-analysis of sodium–glucose cotransporter 2 (SGLT2)
inhibitor outcome trials reported that SGLT2 inhibitors were associated with reduction in the risk of adverse composite kidney outcomes, with moderate heterogeneity
across the trials; however, the endpoints were defined differently across the trials.
Hypothesis: The apparent heterogeneity of the meta-analysis of kidney composite
outcomes of SGLT2 inhibitor trials will be substantially reduced by using a consistent
assessment of sustained ≥40% decline in eGFR/chronic kidney dialysis/transplantation/renal death across trials.
Methods: We performed a meta-analysis of kidney composite outcomes from the
four SGLT2 cardiovascular outcome trial programs conducted in general type 2 diabetes mellitus populations, which included, as a surrogate of progression to kidney
failure, a sustained ≥40% decline in eGFR along with kidney replacement therapy and
kidney death. The trials assessed were VERTIS CV (NCT01986881), CANVAS Program (NCT01032629 and NCT01989754), DECLARE-TIMI 58 (NCT01730534), and
EMPA-REG OUTCOME (NCT01131676).
Results: Data from the trials comprised 42 516 individual participants; overall,
998 composite kidney events occurred. SGLT2 inhibition was associated with a significant reduction in the kidney composite endpoint (HR 0.58 [95% CI 0.51–0.65])
and with a highly consistent effect across the trials (Q statistic p = .64; I
2 = 0.0%).
Conclusions: Our meta-analysis highlights the value of using similarly defined endpoints across trials and supports the finding of consistent protection against kidney
disease progression with SGLT2 inhibitors as a class in patients with type 2 diabetes
mellitus who either have established atherosclerotic cardiovascular disease or are at
high cardiovascular risk with multiple cardiovascular risk factors
Design and baseline characteristics of the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes trial (VERTIS-CV)
Background Ertugliflozin is an inhibitor of sodium-glucose co-transporter-2 (SGLT2), approved in the United States and
European Union to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). The VERTIS cardiovascular (CV)
outcomes trial (NCT01986881) has a primary objective to demonstrate non-inferiority of ertugliflozin versus placebo on major
adverse CV events: time to the first event of CV death, nonfatal myocardial infarction, or nonfatal stroke. Secondary objectives
are to demonstrate superiority of ertugliflozin versus placebo on time to: 1) the composite outcome of CV death or
hospitalization for heart failure (HF); 2) CV death; and 3) the composite outcome of renal death, dialysis/transplant, or
doubling of serum creatinine from baseline.
Methods Patients ≥40 years old with T2DM (HbA1c 7.0–10.5%) and established atherosclerotic cardiovascular disease
(ASCVD) of the coronary, cerebral, and/or peripheral arterial systems, were randomized 1:1:1 to once daily double-blind
placebo, ertugliflozin 5 mg or 15 mg added to existing therapy.
Results 8246 patients were randomized and 8238 received at least 1 dose of investigational product. Mean age was
64.4 years, 11.0% were ≥75 years old, and mean diabetes duration was 12.9 years with screening HbA1c of 8.3%. At entry,
coronary artery disease, cerebrovascular disease, and peripheral arterial disease were present in 76.3%, 23.1%, and 18.8%
of patients, respectively. HF was present in 23.1%, and Stage 3 kidney disease in 21.6% of patients.
Conclusion The results from the VERTIS-CV trial will define the CV and renal safety and efficacy of ertugliflozin in patients
with T2DM and ASCVD. (Am Heart J 2018;206:11-23.
Estimation of the mean when data contain non-ignorable missing values from a random effects model
This paper is concerned with the inference of incomplete data when the missing data process is non-ignorable in the sense of Rubin (Biometrica 38 (1982) 963-974). With the random effects model and the proposed missing data process, the conditions missing at random (MAR) and distinct parameters (DP) are discussed. The impact of the missing data is illustrated by the asymptotic bias of the sample mean based on only the observed data and ignoring the missing data process. Maximum likelihood and moment estimators of the marginal mean are obtained.Missing values random effects model non-ignorable missing data process missing at random distinct parameters EM algorithm ECM algorithm