The impact of covariate imbalance on the size of the logrank test in randomized clinical trials N. Kinukawa, T. Nakamura, K. Akazawa and Y. Nose,Statistics in Medicine 2000;19: 1955-1967

Anemia is common in heart failure (HF) patients and has been well-established as a risk factor for increased risk of HF hospitalization and mortality. Treatment with erythropoietin stimulating agents (ESA) has increased hemoglobin, but outcomes trials are limited and use of ESA has been controversial given disparate results in other populations. This meta-analysis aimed to evaluate the impact of ESA and iron on outcomes in HF patients. A systematic review of four databases was conducted in April 2008 (n = 95 unique trials). Analysis inclusion criteria included randomized controlled trial to ESA/iron with clinically defined HF, yielding 10 eligible trials published between 6/01–3/08. Data was independently extracted and cross-checked for accuracy and reliability (2 investigators). A total of 768 subjects (421 treated and 338 controls) are included (Characteristics in Table 1 ). Randomization to ESA produced a significant improvement in exercise capacity 0.39 standard units [95% CI 0.1– 0.6, p = 0.001], a 5.72% [95% CI 1.2–10.3, p = 0.014] increase in left ventricle ejection fraction and a 0.23 mg/dL [95% CI 0.4 – 0.1 p = 0.001] reduction in serum creatinine. There was no difference in all-cause mortality - RR 0.79 [95% CI 0.49, 1.26, p = 0.320]. Trends were noted in reduced hospitalization rates, decreased brain natriuretic peptide, and improved quality of life. Meta-analysis of randomized studies of treatment of anemia in HF patients suggests significant benefit in exercise capacity, left ventricular ejection fraction, and serum creatinine. There does not appear to be excess mortality with ESA/iron treatment. Despite favorable findings, definitive randomized clinical trials are needed to assess the role of this treatment modality in HF management. Table 1. Baseline Patient and Study Characteristics

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New Paradigms in Polypoidal Choroidal Vasculopathy Management: The Impact of Recent Multicenter, Randomized Clinical Trials

Ophthalmic Surgery Lasers and Imaging Retina ◽

10.3928/23258160-20171215-01 ◽

2018 ◽

Vol 49 (1) ◽

pp. 4-10 ◽

Cited By ~ 5

Author(s):

Colin S. Tan ◽

Seenu M. Hariprasad ◽

Louis W. Lim

Keyword(s):

Clinical Trials ◽

Polypoidal Choroidal Vasculopathy ◽

Randomized Clinical Trials ◽

The Impact ◽

Choroidal Vasculopathy

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Spa-therapy can improve quality of life in chronic musculoskeletal disorder subjects: a narrative review

Journal of restorative medicine and rehabilitation ◽

10.38025/2078-1962-2020-96-2-3-6 ◽

2020 ◽

Vol 96 (2) ◽

pp. 3-6

Author(s):

M.C. Maccarone ◽

G. Magro ◽

U. Solimene ◽

S. Masiero

Keyword(s):

Quality Of Life ◽

Clinical Trials ◽

Randomized Clinical Trials ◽

Thermal Environment ◽

Narrative Review ◽

Spa Therapy ◽

Age Related ◽

Therapy Interventions ◽

The Impact

Chronic Musculoskeletal Disorders (MSDs) are age-related conditions, linked to functional impairment and decreased quality of life (QoL). As a result of the increased life expectancy in Europe, great attention has been focused on investigating the impact of these diseases on QoL. Thermal environment is a suitable place for providing interventions (mud therapy, bath, exercise, etc.) for chronic MSD patients. Our narrative review aims to assess if Spa therapy may improve QoL in patients with chronic MSDs. We searched randomized clinical trials and clinical trials screening PubMed and Google Scholar databases from 2016 up to March 2020. We included 14 trials testing Spa therapy interventions concerning osteoarthritis, rheumatoid arthritis, chronic shoulder pain and fibromyalgia. In conclusion, even though limitations must be considered, evidence shows that Spa therapy, especially in combination with rehabilitation approach, can significantly improve QoL of patients with chronic MSDs.

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Impact of Peritoneal Dialysis Dose Guidelines on Clinical Outcomes

Peritoneal Dialysis International ◽

10.1177/089686080502503s24 ◽

2005 ◽

Vol 25 (3_suppl) ◽

pp. 95-98 ◽

Cited By ~ 7

Author(s):

David N. Churchill

Keyword(s):

Clinical Trials ◽

Peritoneal Dialysis ◽

Clinical Practice ◽

Adverse Effects ◽

Randomized Clinical Trials ◽

Intervention Group ◽

The United States ◽

Dialysis Dose ◽

Middle Molecules ◽

The Impact

The objective was to review the rationale for the Kidney Disease Outcomes Quality Initiative (K/DOQI) recommendations for adequacy of peritoneal dialysis and to evaluate the impact of these recommendations on clinical practice and patient survival. The K/DOQI recommendations were based on large observational studies; the target weekly Kt/V value of 2.0 assumed equivalence of peritoneal and renal clearances. This assumption is no longer considered correct. The impact on clinical practice was evaluated by an examination of temporal trends before and after publication of the guidelines in 1997. In the United States and The Netherlands, there had been a trend toward increased delivered total Kt/V prior to 1997, and there was no acceleration in this trend after 1997. Two randomized clinical trials have implemented these guidelines with increased peritoneal Kt/V (or creatinine clearance) used to achieve the K/DOQI target in the intervention group. This was not associated with improved survival, compared to a lower Kt/V, in either of the randomized clinical trials. Among the explanations for the failure to improve outcome are potential adverse effects of increasing the dialysis dose. These include increased intraperitoneal pressure associated with increased exchange volume, failure to increase clearance of middle molecules, and increased exposure to glucose. Strategies that increase peritoneal clearance without exposure to these potential adverse effects include more-frequent exchanges rather than increased exchange volume, and decreased exposure to glucose and glucose degradation products. Pending such studies, current K/DOQI guidelines should be updated in a timely manner.

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The impact of data errors on the outcome of randomized clinical trials

Clinical Trials ◽

10.1177/1740774517716158 ◽

2017 ◽

Vol 14 (5) ◽

pp. 499-506 ◽

Cited By ~ 9

Author(s):

Marc Buyse ◽

Pierre Squifflet ◽

Elisabeth Coart ◽

Emmanuel Quinaux ◽

Cornelis JA Punt ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Trials ◽

Metastatic Colorectal Cancer ◽

Randomized Clinical Trials ◽

Systematic Errors ◽

Age Related Macular Degeneration ◽

Random Errors ◽

Significant Treatment ◽

Age Related ◽

The Impact

Background/aims Considerable human and financial resources are typically spent to ensure that data collected for clinical trials are free from errors. We investigated the impact of random and systematic errors on the outcome of randomized clinical trials. Methods We used individual patient data relating to response endpoints of interest in two published randomized clinical trials, one in ophthalmology and one in oncology. These randomized clinical trials enrolled 1186 patients with age-related macular degeneration and 736 patients with metastatic colorectal cancer. The ophthalmology trial tested the benefit of pegaptanib for the treatment of age-related macular degeneration and identified a statistically significant treatment benefit, whereas the oncology trial assessed the benefit of adding cetuximab to a regimen of capecitabine, oxaliplatin, and bevacizumab for the treatment of metastatic colorectal cancer and failed to identify a statistically significant treatment difference. We simulated trial results by adding errors that were independent of the treatment group (random errors) and errors that favored one of the treatment groups (systematic errors). We added such errors to the data for the response endpoint of interest for increasing proportions of randomly selected patients. Results Random errors added to up to 50% of the cases produced only slightly inflated variance in the estimated treatment effect of both trials, with no qualitative change in the p-value. In contrast, systematic errors produced bias even for very small proportions of patients with added errors. Conclusion A substantial amount of random errors is required before appreciable effects on the outcome of randomized clinical trials are noted. In contrast, even a small amount of systematic errors can severely bias the estimated treatment effects. Therefore, resources devoted to randomized clinical trials should be spent primarily on minimizing sources of systematic errors which can bias the analyses, rather than on random errors which result only in a small loss in power.

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Fundamental dilemmas of the randomized clinical trial process: results of a survey of the 1,737 Eastern Cooperative Oncology Group investigators.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.9.1796 ◽

1994 ◽

Vol 12 (9) ◽

pp. 1796-1805 ◽

Cited By ~ 104

Author(s):

K M Taylor ◽

M L Feldstein ◽

R T Skeel ◽

K J Pandya ◽

P Ng ◽

...

Keyword(s):

Clinical Trials ◽

Randomized Clinical Trials ◽

Eastern Cooperative Oncology Group ◽

Oncology Group ◽

Future Design ◽

Actual Patient ◽

Critical Issues ◽

Accrual Rate ◽

The Impact ◽

Patient Accrual

PURPOSE We studied oncologists' attitudes and behavior with regard to their participation in randomized clinical trials. METHODS We surveyed the 1,737 physician members of the Eastern Cooperative Oncology Group (ECOG) using the Physician Orientation Profile (POP), a self-administered mailed questionnaire. A response rate of 86% was achieved (1,485 of 1,737); each physician's actual patient accrual was recorded. RESULTS All respondents indicated that they had a systematic pattern of patient preselection for entry onto trials beyond the formal inclusion/exclusion trial criteria. Eighty-nine percent stated that improving patient quality of life rather than prolonging survival was more personally satisfying. Sixty-two percent did not enter a single patient during the 12-month period following the survey, while 10% entered 80% of all patients during that time. Physicians overestimated their accrual rate by a factor of 6. Eighty-three percent defined randomization and adherence to trial protocol as a serious challenge to their ability to make individualized treatment decisions. CONCLUSION This study raises questions regarding the following: (1) the perceived generalizability of trial findings, (2) the role of end points other than survival for clinical trials, (3) the consequences of physician overestimation of patient accrual, and (4) the impact of randomized trials on the behavior of clinicians. Further investigation into these critical issues will provide meaningful recommendations to enhance the future design, implementation, and conduct of randomized clinical trials in cancer.

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