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Translational Behavioral Medicine Dec 2013There has been a recent surge of eHealth programs in cancer and other content areas, but few reviews have focused on the methodologies and designs employed in these... (Review)
Review
There has been a recent surge of eHealth programs in cancer and other content areas, but few reviews have focused on the methodologies and designs employed in these studies. We conducted a systematic review of studies on eHealth interventions on cancer prevention and control published between 2001 and 2010 applying the Pragmatic Explanatory Continuum Indicator Summary (PRECIS) criteria and external validity components from the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework. We identified 113 studies that focused on cancer prevention and control of eHealth interventions. Most studies fell midway along the explanatory/pragmatic trial continuum, but few reported on various practical feasibility criteria for translation. Despite vast interest in cancer eHealth and the applied nature of this field, few studies considered key external validity issues. There is a need for use of alternative pragmatic study designs and transparent reporting of external validity components to produce more rapid and generalizable results.
PubMed: 24294327
DOI: 10.1007/s13142-013-0224-1 -
Cancer Treatment Reviews Jun 2022Research on therapeutic strategies for patients with unknown primary cancer (CUP) has been underwhelming. This paper summarized and evaluated the CUP therapeutic... (Review)
Review
BACKGROUND
Research on therapeutic strategies for patients with unknown primary cancer (CUP) has been underwhelming. This paper summarized and evaluated the CUP therapeutic research over the previous five years. Based on this evaluation, recommendations for clinical trial designs are made to improve the impact of CUP research on patients.
METHODS
Published and ongoing research were evaluated. PubMed was searched from January 1, 2015, to November 1, 2021. The start date of 2015 was chosen to identify research published after ESMO issued new diagnostic and therapeutic guidelines. The US National Library of Medicine indexed ongoing clinical trials.
FINDINGS
Of the 244 CUP studies indexed in PubMed, 11.9% were prospective studies, and 4.9% were clinical trials. The review protocol deemed 65 publications eligible for full-text review. Eleven studies evaluating therapeutic regimens were retained. The two prospective studies and non-randomized trials showed promising outcomes for site-specific treatments. Randomized clinical trials were less promising; however, the trials had recruitment challenges resulting in biased accrual and the inability to keep pace with advancing diagnostics and therapeutics. Most of the 35 ongoing studies were phase II single-arm trials assessing immune checkpoint inhibitors (ICI) or site-specific therapies among CUP patients with suspected favorable prognoses.
CONCLUSION
Our evaluation suggests two prospective clinical trial designs that addressed recent study design and recruitment challenges. A visionary approach uses a multi-arm, multistage randomized trial to address rapid advancements in diagnosis and therapy. A pragmatic approach utilizes a single-arm trial with historical controls to overcome comparison group and recruitment challenges.
Topics: Humans; Immune Checkpoint Inhibitors; Prospective Studies; Research Design
PubMed: 35569387
DOI: 10.1016/j.ctrv.2022.102407 -
International Journal of Geriatric... May 2014We investigated the proportion of people with dementia who are eligible for and willing to participate in intervention studies. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We investigated the proportion of people with dementia who are eligible for and willing to participate in intervention studies.
METHODS
We systematically reviewed 12 studies fitting predetermined criteria, reporting eligibility or participation rates for dementia intervention trials or intervention studies that sought to increase recruitment. We assessed the study validity using a checklist, reported trial eligibility and participation rates and meta-analysed these where appropriate.
RESULTS
In higher quality studies, 26% [95% confidence interval 19-35%] of people with Alzheimer's disease (AD) attending memory clinics or receiving antidementia medication were eligible for industry drug trials, and 43% of eligible people agreed to participate in one study, suggesting 11% of these populations would take part in drug trials if approached. There was replicated, higher quality evidence that younger people, men and those with more education were more likely to be eligible for AD drug trials. No randomised controlled trials have investigated how to increase recruitment to dementia intervention studies.
CONCLUSION
One in 10 people with AD or taking donepezil would, according to best available evidence, take part in industry drug trials if approached. We found no data regarding non-pharmacological intervention or pragmatic drug trial recruitment, but eligibility and participation rates for these studies are probably higher. If international studies are extrapolated to the UK, they suggest the national target of recruiting 10% of people with dementia diagnoses to research may be achieved through a nationwide policy of asking all people with dementia and their carers for consent to be approached for research participation.
Topics: Cholinesterase Inhibitors; Dementia; Eligibility Determination; Female; Humans; Male; Patient Participation; Patient Selection; Randomized Controlled Trials as Topic; Research Design; United Kingdom
PubMed: 24706605
DOI: 10.1002/gps.4034 -
BMJ Open Jul 2020To synthesise findings from randomised controlled trials (RCTs) of interventions aimed at increasing medication adherence in individuals with type 2 diabetes (T2DM)... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To synthesise findings from randomised controlled trials (RCTs) of interventions aimed at increasing medication adherence in individuals with type 2 diabetes (T2DM) and/or cardiovascular disease (CVD). And, in a novel approach, to compare the intervention effect of studies which were categorised as being more pragmatic or more explanatory using the Pragmatic-Explanatory Continuum Indicator Summary-2 (PRECIS-2) tool, to identify whether study design affects outcomes. As explanatory trials are typically held under controlled conditions, findings from such trials may not be relatable to real-world clinical practice. In comparison, pragmatic trials are designed to replicate real-world conditions and therefore findings are more likely to represent those found if the intervention were to be implemented in routine care.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Ovid Medline, Ovid Embase, Web of Science and CINAHL from 1 January 2013 to 31 December 2018.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
RCTs lasting ≥3 months (90 days), involving ≥200 patients in the analysis, with either established CVD and/or T2DM and which measured medication adherence. From 4403 citations, 103 proceeded to full text review. Studies published in any language other than English and conference abstracts were excluded.
MAIN OUTCOME MEASURE
Change in medication adherence.
RESULTS
Of 4403 records identified, 34 studies were considered eligible, of which 28, including 30 861 participants, contained comparable outcome data for inclusion in the meta-analysis. Overall interventions were associated with an increase in medication adherence (OR 1.57 (95% CI: 1.33 to 1.84), p<0.001; standardised mean difference 0.24 (95% CI: -0.10 to 0.59) p=0.101). The effectiveness of interventions did not differ significantly between studies considered pragmatic versus explanatory (p=0.598), but did differ by intervention type, with studies that included a multifaceted rather than a single-faceted intervention having a more significant effect (p=0.010). The analysis used random effect models and used the revised Cochrane Risk of Bias Tool to assess study quality.
CONCLUSIONS
In this meta-analysis, interventions were associated with a significant increase in medication adherence. Overall multifaceted interventions which included an element of education alongside regular patient contact or follow-up showed the most promise. Effectiveness of interventions between pragmatic and explanatory trials was comparable, suggesting that findings can be transferred from idealised to real-word conditions.
PROSPERO REGISTRATION NUMBER
CRD42017059460.
Topics: Cardiovascular Diseases; Humans; Medication Adherence
PubMed: 32709649
DOI: 10.1136/bmjopen-2019-036575 -
The Cochrane Database of Systematic... Jan 2012Antipsychotic medication remains the mainstay of treatment for schizophrenia and has been in use for a long time. As evidenced by ongoing research and partial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic medication remains the mainstay of treatment for schizophrenia and has been in use for a long time. As evidenced by ongoing research and partial effectiveness of the antipsychotics on cognitive and negative symptoms, the search is on for drugs that may improve these domains of functioning for someone suffering from schizophrenia. Acetylcholinesterase inhibitors have long been in use for treating cognitive symptoms of dementia.
OBJECTIVES
The aim of the review was to evaluate the clinical effects, safety and cost effectiveness of acetylcholinesterase inhibitors for treating people with schizophrenia
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Register (February 2009), and inspected the references of all identified studies for further trials.
SELECTION CRITERIA
We included all clinical randomised trials comparing acetylcholinesterase inhibitors with antipsychotics or placebo either alone, or in combination, for schizophrenia and schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For dichotomous data, we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat (ITT) basis based on a random-effects model. For continuous data, we calculated mean differences (MD), again based on a random-effects model.
MAIN RESULTS
The acetylcholinesterase inhibitor plus antipsychotic showed benefit over antipsychotic and placebo in the following outcomes.1. Mental state - PANSS negative symptoms average end point score (2 RCTs, n = 31, MD -1.69 95% CI -2.80 to -0.57), PANSS General Psychopathology average end point score (2 RCTs, n = 31, MD -3.86 95% CI -5.40 to -2.32), and improvement in depressive symptoms showed at least by one short-term study as measured by CDSS scale (data skewed).2. Cognitive domains - attention, (1 RCT, n = 73, MD 1.20 95% CI 0.14 to 2.26), visual memory (2 RCTs, n = 48 , MD 1.90 95% CI 0.52 to 3.28), verbal memory and language (3 RCTs, n = 42, MD 3.46 95% CI 0.67 to 6.26) and executive functioning (1 RCT, n = 24, MD 17.10 95% CI 0.70 to 33.50).3. Tolerability - EPSE: AIMS, (1 RCT, n = 35, MD 1.50 95% CI 1.04 to 1.96).No difference was noted between the two arms in other outcomes. The overall rate of participants leaving studies early was low (13.6 %) and showed no clear difference between the two groups.
AUTHORS' CONCLUSIONS
The results seem to favour the use of acetylcholinesterase inhibitors in combination with antipsychotics on a few domains of mental state and cognition, but because of the various limitations in the studies as mentioned in the main text, the evidence is weak. This review highlights the need for large, independent, well designed, conducted and reported pragmatic randomised studies.
Topics: Antipsychotic Agents; Cholinesterase Inhibitors; Donepezil; Galantamine; Humans; Indans; Phenylcarbamates; Piperidines; Psychotic Disorders; Randomized Controlled Trials as Topic; Rivastigmine; Schizophrenia; Schizophrenic Psychology
PubMed: 22258978
DOI: 10.1002/14651858.CD007967.pub2 -
Pediatric Critical Care Medicine : a... Jun 2013To systematically review randomized controlled trials (RCTs) of steroids conducted in children with fluid and/or vasoactive medication-dependent shock and evaluate and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically review randomized controlled trials (RCTs) of steroids conducted in children with fluid and/or vasoactive medication-dependent shock and evaluate and report on the quality and clinical and methodological heterogeneity of included trials.
DATA SOURCES
MEDLINE (1946 to January Week 2, 2012), Embase (1947-January 20, 2012), Cochrane Central Register of Controlled Trials (through January 2012), and reference lists of retrieved publications. No language restrictions were applied.
STUDY SELECTION
We included only RCTs reporting on steroid use and clinical outcomes in pediatric shock.
DATA EXTRACTION
Study characteristics, interventions, and outcomes were retrieved by three independent reviewers. Pooled relative risks and 95% CIs were calculated using a random effects model.
DATA SYNTHESIS
We identified 535 citations from which 13 full-text articles were retrieved for assessment. Eight articles evaluating a total of 447 children were selected for review. The median trial size was 67 patients (range, 28-98). Seven of the eight trials were published prior to 1996, and all trials were conducted in the developing world, and six of eight trials were in the setting of dengue shock. We found methodological issues related to allocation concealment, blinding and reporting of co-interventions, and outcome data among the included trials along with varying types, doses, timings, and duration of steroids making it difficult to compare outcomes. The overall meta-analysis showed no difference in mortality rates between those who did and did not receive steroids (relative risks, 0.744 [95% CI, 0.475-1.165]; p = 0.197).
CONCLUSIONS
The literature on the use of steroids in pediatric shock is limited in amount and methodological quality and demonstrates conflicting results. The limited evidence on which current guidelines are based strongly supports the need for a well-designed, pragmatic randomized controlled trial on the use of steroids in pediatric shock to inform future guidelines.
Topics: Adrenal Cortex Hormones; Cardiovascular Agents; Child; Fluid Therapy; Humans; Intensive Care Units, Pediatric; Randomized Controlled Trials as Topic; Shock, Septic
PubMed: 23867428
DOI: 10.1097/PCC.0b013e31828a8125 -
International Journal of Colorectal... Oct 2023A watch-and-wait (WW) strategy or surgery for low to intermediate rectal cancer that has reached clinical complete remission (cCR) after neoadjuvant chemotherapy (nCRT)... (Meta-Analysis)
Meta-Analysis Review
Oncologic outcomes of watch-and-wait strategy or surgery for low to intermediate rectal cancer in clinical complete remission after adjuvant chemotherapy: a systematic review and meta-analysis.
BACKGROUND
A watch-and-wait (WW) strategy or surgery for low to intermediate rectal cancer that has reached clinical complete remission (cCR) after neoadjuvant chemotherapy (nCRT) or total neoadjuvant therapy (TNT) has been widely used in the clinic, but both treatment strategies are controversial.
OBJECTIVE
The aim of this study was to compare the oncologic outcomes of a watch-and-wait strategy or a surgical approach to treat rectal cancer in complete remission and to report the evidence-based clinical advantages of the two treatment strategies.
METHODS
Seven national and international databases were searched for clinical trials comparing the watch-and-wait strategy with surgical treatment for oncological outcomes in patients with rectal cancer in clinical complete remission.
RESULTS
In terms of oncological outcomes, there was no significant difference between the watch-and-wait strategy and surgical treatment in terms of overall survival (OS) (HR = 0.92, 95% CI (0.52, 1.64), P = 0.777), and subgroup analysis showed no significant difference in 5-year disease-free survival (5-year DFS) between WW and both local excision (LE) and radical surgery (RS) (HR = 1.76, 95% CI (0.97, 3.19), P = 0.279; HR = 1.98, 95% CI (0.95, 4.13), P = 0.164), in distant metastasis rate (RR = 1.12, 95% CI (0.73, 1.72), P = 0.593), mortality rate (RR = 1.62, 95% CI (0.93, 2.84), P = 0.09), and organ preservation rate (RR = 1.05, 95% CI (0.94, 1.17), P = 0.394) which were not statistically significant and on the outcome indicators of local recurrence rate (RR = 2.09, 95% CI (1.44, 3.03), P < 0.001) and stoma rate (RR = 0.35, 95% CI (0.20, 0.61), P < 0.001). There were significant differences between the WW group and the surgical treatment group.
CONCLUSION
There were no differences in OS, 5-year DFS, distant metastasis, and mortality between the WW strategy group and the surgical treatment group. The WW strategy did not increase the risk of local recurrence compared with local resection but may be at greater risk of local recurrence compared with radical surgery, and the WW group was significantly better than the surgical group in terms of stoma rate; the WW strategy was evidently superior in preserving organ integrity compared to radical excision. Consequently, for patients who exhibit a profound inclination towards organ preservation and the evasion of stoma formation in the scenario of clinically complete remission of rectal cancer, the WW strategy can be contemplated as a pragmatic alternative to surgical interventions. It is, however, paramount to emphasize that the deployment of such a strategy should be meticulously undertaken within the ambit of a multidisciplinary team's management and within specialized centers dedicated to rectal cancer management.
Topics: Humans; Rectal Neoplasms; Remission Induction; Disease-Free Survival; Chemoradiotherapy; Digestive System Surgical Procedures; Neoadjuvant Therapy; Watchful Waiting; Neoplasm Recurrence, Local; Treatment Outcome
PubMed: 37787779
DOI: 10.1007/s00384-023-04534-2 -
Journal of Clinical Oncology : Official... Dec 2012The objectives of this article are (1) to examine the similarities and differences between comparative effectiveness research (CER) and evidence-based medicine (EBM);... (Review)
Review
PURPOSE
The objectives of this article are (1) to examine the similarities and differences between comparative effectiveness research (CER) and evidence-based medicine (EBM); (2) to describe the implications of CER for systematic review methodologies in oncology; and (3) to address the transition from systematic reviews to guideline development and the implications of CER in this process.
METHOD
An analysis of the principles and methods of CER was undertaken in light of EBM, systematic reviews, and guidelines.
RESULTS AND CONCLUSION
There is considerable overlap between the principles and methods of the two paradigms. The focus on best care options in the context of routine practice is a more central tenet of the CER paradigm. Thus, its value is not that it is the first paradigm to recognize the importance of a patient-focused approach in the research community, but rather, given the attention it has garnered, the CER paradigm may be precisely the reminder and push required to: one, influence how systematic questions are framed so that a more patient-relevant perspective is achieved; two, broaden the types of study designs that are valued and to include those, such as pragmatic trials and observational studies, that are better able to answer effectiveness questions; three, accelerate the development and application of statistical methods that enable indirect comparisons of cancer care options; and four, create clinical practice guidelines that are better positioned to improve quality of care and system performance. Over time, we will see if the CER paradigm lives up to its potential.
Topics: Comparative Effectiveness Research; Humans; Practice Guidelines as Topic; Review Literature as Topic
PubMed: 23071227
DOI: 10.1200/JCO.2012.42.1644 -
Neurology Apr 2016We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS).
OBJECTIVE
We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS).
METHODS
We held an international workshop, informed by a systematic review of the incidence and prevalence of comorbidity in MS and an international survey about research priorities for studying comorbidity including their relation to clinical trials in MS.
RESULTS
We recommend establishing age- and sex-specific incidence estimates for comorbidities in the MS population, including those that commonly raise concern in clinical trials of immunomodulatory agents; shifting phase III clinical trials of new therapies from explanatory to more pragmatic trials; describing comorbidity status of the enrolled population in publications reporting clinical trials; evaluating treatment response, tolerability, and safety in clinical trials according to comorbidity status; and considering comorbidity status in the design of pharmacovigilance strategies.
CONCLUSION
Our recommendations will help address knowledge gaps regarding comorbidity that interfere with the ability to interpret safety in monitored trials and will enhance the generalizability of findings from clinical trials to "real world" settings where the MS population commonly has comorbid conditions.
Topics: Clinical Trials as Topic; Comorbidity; Humans; Multiple Sclerosis
PubMed: 26888986
DOI: 10.1212/WNL.0000000000002471 -
The Cochrane Database of Systematic... 2000Typical antipsychotic drugs are widely used as first line treatment for people with schizophrenia. The atypical class of antipsychotic drugs, however, is making... (Review)
Review
BACKGROUND
Typical antipsychotic drugs are widely used as first line treatment for people with schizophrenia. The atypical class of antipsychotic drugs, however, is making important inroads into this approach and zotepine is one such compound. It is a dopamine antagonist and claimed to be to be particularly effective for negative symptoms
OBJECTIVES
To determine the effects of zotepine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses.
SEARCH STRATEGY
Electronic searches of Biological Abstracts (1980-1999), CINAHL (1982-1999), The Cochrane Library (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), Dialog Corporation Datastar service (1999), MEDLINE (1966-1999), and PsycLIT (1974-1999) were undertaken. References of all identified studies were searched for further trials. Knoll Pharmaceuticals and authors of trials were contacted.
SELECTION CRITERIA
All randomised clinical trials that compared zotepine to other treatments for people with schizophrenia or other psychoses were included.
DATA COLLECTION AND ANALYSIS
Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. Data were excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the relative risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) and numbers needed to harm (NNH), were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity.
MAIN RESULTS
All outcomes were short term (4-12 weeks). Limited data suggest that zotepine is an antipsychotic, at least as effective as typical drugs. Mental state measures of 'no clinically important improvement' favour zotepine when compared to other active drugs (n=356, RR 0.8 CI 0.7-0.9, NNT 7 CI 4-22). About one third of people in both zotepine and control groups left the studies before trial completion. Zotepine may result in less movement disorder adverse effects than typical antipsychotic drugs. Trials have not highlighted clear differences between zotepine and other atypical drugs.
REVIEWER'S CONCLUSIONS
Zotepine may be a valuable addition to the increasing ranks of atypical antipsychotic drugs. More data from already existing studies is urgently needed to increase the confidence in the findings of this review. New data from well planned, conducted and reported long term pragmatic randomised trials are necessary. Otherwise clinical use of zotepine will be based on speculation on the meaning of the findings of short explanatory trials for everyday practice.
Topics: Antipsychotic Agents; Dibenzothiepins; Humans; Psychotic Disorders; Schizophrenia
PubMed: 10796671
DOI: 10.1002/14651858.CD001948