The effect of poor compliance and treatment side effects on sample size requirements in randomized clinical trials

1994 ◽  
Vol 4 (2) ◽  
pp. 223-232 ◽  
Author(s):  
Kenneth B. Schechtman ◽  
Mae O. Gordon
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Sample Size ◽  
Randomized Clinical Trials ◽  
Poor Compliance ◽  
Treatment Side Effects

Statistical power of negative randomized clinical trials (RCTs) presented at the American Society of Clinical Oncology (ASCO) Annual Meetings

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6516-6516
Author(s):  
P. Bedard ◽  
M. K. Krzyzanowska ◽  
M. Pintilie ◽  
I. F. Tannock
Keyword(s):  
Clinical Trials ◽  
Sample Size ◽  
Annual Meeting ◽  
Primary Endpoint ◽  
Effect Size ◽  
Statistical Power ◽  
Randomized Clinical Trials ◽  
Medium Effect ◽  
Post Hoc ◽  
Adequate Sample Size

6516 Background: Underpowered randomized clinical trials (RCTs) may expose participants to risks and burdens of research without scientific merit. We investigated the prevalence of underpowered RCTs presented at ASCO annual meetings. Methods: We surveyed all two-arm parallel phase III RCTs presented at the ASCO annual meeting from 1995–2003 where differences for the primary endpoint were non-statistically significant. Post hoc calculations were performed using a power of 80% and a=0.05 (two-sided) to determine the sample size required to detect a small, medium, and large effect size between the two groups. For studies reporting a proportion or time to event as a primary endpoint, effect size was expressed as an odds ratio (OR) or hazard ratio (HR) respectively, with a small effect size defined as OR/HR=1.3, medium effect size OR/HR=1.5, and large effect OR/HR=2.0. Logistic regression was used to identify factors associated with lack of statistical power. Results: Of 423 negative RCTs for which post hoc sample size calculations could be performed, 45 (10.6%), 138 (32.6%), and 333 (78.7%) had adequate sample size to detect small, medium, and large effect sizes respectively. Only 35 negative RCTs (7.1%) reported a reason for inadequate sample size. In a multivariable model, studies presented at plenary or oral sessions (p<0.0001) and multicenter studies supported by a co-operative group were more likely to have adequate sample size (p<0.0001). Conclusion: Two-thirds of negative RCTs presented at the ASCO annual meeting do not have an adequate sample to detect a medium-sized treatment effect. Most underpowered negative RCTs do not report a sample size calculation or reasons for inadequate patient accrual. No significant financial relationships to disclose.

Placebo and nocebo effects in randomized double-blind clinical trials for fatigue in advanced cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9640-9640
Author(s):  
M. de la Cruz ◽  
D. Hui ◽  
H. A. Parsons ◽  
P. Lynn ◽  
C. Parker ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Randomized Clinical Trials ◽  
Placebo Response ◽  
Well Being ◽  
Advanced Cancer Patients ◽  
Edmonton Symptom Assessment Scale ◽  
Nocebo Effects

9640 Background: We have previously reported significant placebo response in randomized controlled treatment trials for cancer related fatigue (CRF). We conducted a retrospective study to determine the frequency and predictors of response to placebo and nocebo effect in patients with CRF. Methods: We reviewed patients that received placebo in two previous randomized clinical trials conducted by our group and determined the proportion of patients who demonstrated clinical response to fatigue using an increase (ΔFACIT-F score) > 7 from baseline to day 8, and those with nocebo response as those who reported side effects. Baseline patient characteristics and symptoms recorded from the Edmonton Symptom Assessment Scale (ESAS) were analyzed to determine their association with placebo and nocebo effects. Results: A total of 105 advanced cancer patients received placebo. 59 (56%) patients responded to placebo (median Δ FACIT-F score of 22). Worse baseline anxiety and well-being subscale score (univariate) and well-being (multivariate, MR) were significantly associated with placebo response. Common side effects reported were insomnia (79%), anorexia (53%), nausea (38%) and restlessness (34%). MR analysis showed that worse baseline (ESAS) sleep, appetite, nausea, and restless are associated with increased reporting of these side effects ( Table ). Conclusions: Nearly half of advanced cancer patients enrolled in the fatigue trials responded to placebo. Worse physical well-being score was associated with placebo response. Patients experiencing specific symptoms at baseline were more likely to report these as side effects of the medication. These findings should be considered in fatigue clinical trial design. [Table: see text] No significant financial relationships to disclose.

scholarly journals Outcome Measures for Clinical Drug Trials in Autism

CNS Spectrums ◽  
2004 ◽  
Vol 9 (1) ◽  
pp. 36-47 ◽  
Author(s):  
Michael G. Aman ◽  
Sherie Novotny ◽  
Carole Samango-Sprouse ◽  
Luc Lecavalier ◽  
Elizabeth Leonard ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Randomized Clinical Trials ◽  
Vital Signs ◽  
Autism Spectrum ◽  
Spectrum Disorders ◽  
Age Range ◽  
Clinical Drug ◽  
Cognitive Data ◽  
Core Features

ABSTRACTThis paper identifies instruments and measures that may be appropriate for randomized clinical trials in participants with autism spectrum disorders (ASDs). The Clinical Global Impressions scale was recommended for all randomized clinical trials. At this point, however, there is no “perfect” choice of outcome measure for core features of autism, although we will discuss five measures of potential utility. Several communication instruments are recommended, based in part on suitability across the age range. In trials where the intention is to alter core features of ASDs, adaptive behavior scales are also worthy of consideration. Several “behavior complexes” common to ASDs are identified, and instruments are recommended for assessment of these. Given the prevalence of cognitive impairment in ASDs, it is important to assess any cognitive effects, although cognitive data from ASD randomized clinical trials, thus far, are minimal. Guidance from trials in related pharmacologic areas and behavioral pharmacology may be helpful. We recommend routine elicitation of side effects, height and weight, vital signs, and (in the case of antipsychotics) extrapyramidal side-effects assessment. It is often appropriate to include laboratory tests and assessments for continence and sleep pattern.

scholarly journals The Impact of Pegylated Liposomal Doxorubicin in Recurrent Ovarian Cancer : An Updated Meta-Analysis of Randomized Clinical Trials

2021 ◽  
Author(s):  
Xin-Ru Li ◽  
Yi Zhu ◽  
Guo-Nan Zhang ◽  
Jian-Ming Huang ◽  
Li-Xia Pei
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Side Effects ◽  
Confidence Level ◽  
Liposomal Doxorubicin ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Pegylated Liposomal Doxorubicin ◽  
Recurrent Ovarian Cancer ◽  
Cochrane Library

Abstract Background: Pegylated Liposomal Doxorubicin (PLD) could improve the survival rate of patients with recurrent ovarian cancer in previous meta-analysis studies. The aim of the present meta-analysis was to further update the role of PLD in the treatment of recurrent ovarian cancer.Methods: Literature search was performed by using the electronic databases Medicine, EMBASE, Web of Science, and Cochrane library until 27 July 2020. We only restricted the randomized clinical trials. Study specific hazard ratios and 95% confidence level (HR/95% CI), risk ratios and 95% confidence level (RR/95% CI), were pooled using a random effect model. Results: 10 studies (12 trials) were included after screening of 940 articles. We categorized the eligible studies into two groups: the doublet regimens (four trials, 1767 patients) resulted that PLD plus carboplatin(carbo) provided superior progression free survival (PFS) (HR, 0.85; 95% CI, 0.74-0.97) and similar overall survival (OS) (HR, 1.00; 95% CI, 0.88-1.14) compared PAC plus carbo. PLD plus carboplatin was associated with significantly more anemia and Thrombocytopenia, other side effects well-tolerated. In platin resistant patients, the monotherapy regimens (eight trials, 1980 patients) resulted that PLD had similar PFS (HR, 1.02; 95% CI, 0.90–1.16) and OS (HR, 0.88; 95% CI, 0.77–1.01) to other monotherapies. PLD alone was more associated with mucositis/stomatitis and hand-foot syndrome, other side effects well-tolerated.Conclusion: In platinum-sensitive recurrent ovarian cancer, PLD plus carbo is more effective than PAC plus carbo. In platinum-resistant or refractory recurrent ovarian cancer, PLD has similar survival to others monotherapies. For side effects, PLD plus carbo or monotherapy chemotherapy both were well-tolerated.

scholarly journals Existing and Emerging Approaches to Treating Chronic Inflammatory Demyelinating Polyneuropathy

US Neurology ◽  
2019 ◽  
Vol 15 (1) ◽  
pp. 33
Author(s):  
Brannagan III Thomas H ◽  
Khosro Farhad ◽  
Inna Kleyman ◽  
Megan Leitch ◽  
Rebecca Traub ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Randomized Clinical Trials ◽  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Neurological Diseases ◽  
Demyelinating Polyneuropathy ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Inflammatory Demyelinating Polyneuropathy

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare disabling disease with an incompletely understood autoimmune etiology. Differentiating the condition from other neurological diseases can be challenging and appropriate treatment is often delayed. Intravenous immunoglobulin (IVIg), plasmapheresis, corticosteroids and subcutaneous immunoglobulin (SCIg) have all been demonstrated to be beneficial in placebo-controlled, randomized clinical trials. Corticosteroids, including methylprednisolone and dexamethasone are effective and frequently used in CIDP but their long-term use is limited by side effects. One of the most commonly prescribed treatments for CIDP is IVIg which diminishes inflammatory processes and prevents disease progression. Treatment with IVIg has proven effective in randomized, double blind, placebo controlled, clinical trials and the results support its use in CIDP. For some patients, the benefit of IVIg, is limited by the frequency of infusions and systemic side effects such as flu-like symptoms, headache, and nausea. Other effective treatments for CIDP include corticosteroids that are associated with serious side effects in long-term use and plasmapheresis which requires specialized facilities. More recently, SCIg has been demonstrated in double blind, placebo-controlled studies to be effective for maintenance use in CIDP in patients whose disease has been controlled by IVIg. In a large clinical trial, 0.2 g/kg and 0.4 g/kg body weight doses of 20% SCIg equivalent to 1 mL/kg or 2 mL/kg, respectively, administered weekly, demonstrated efficacy in CIDP and were well tolerated. Immunomodulating treatments such as cyclophosphamide, mycophenolate mofetil and rituximab have also shown efficacy in select populations with CIDP.

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