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Fertility and Sterility Jan 2014To examine and compare differences, if any, between industry- and nonindustry-sponsored clinical trials on endometriosis and to evaluate the effect of prior published... (Review)
Review
OBJECTIVE
To examine and compare differences, if any, between industry- and nonindustry-sponsored clinical trials on endometriosis and to evaluate the effect of prior published positive preclinical results, or lack thereof, on trial status.
DESIGN
Cross-sectional study of clinical trials on endometriosis that evaluate drugs/biologicals registered at ClinicalTrials.gov as of July 3, 2013.
SETTING
University-affiliated hospital.
PATIENT(S)
None.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
Trial status, size, phase, and duration; use of comparator groups; drug classes, number of arms, targeting conditions; and presence or absence of prior positive preclinical results before the launch of the trial.
RESULT(S)
Eighty trials were identified. The trials sponsored by industry and non-industry have distinct features, differing in trial status, phase, comparator, drug classes, number of arms, trial size, and duration. The phase II/III trials are predominantly industry supported, but these trials frequently use placebo as the comparator. Trials launched without prior published preclinical results do not seem to fare well, although the presence of such studies is no guarantee for success.
CONCLUSION(S)
Questions as to whether the drug on trial is truly superior to the best available drug or of its cost-benefit profile are overlooked in most cases. There seems to be a deluge of "me-too" drugs with equivocal superiority over existing drugs and cost-benefit profiles. Because clinical trials are time-consuming, no blockbuster drug for endometriosis seems to be on the horizon yet.
Topics: Aromatase Inhibitors; Clinical Trials as Topic; Cross-Sectional Studies; Endometriosis; Female; Hormone Antagonists; Humans
PubMed: 24112527
DOI: 10.1016/j.fertnstert.2013.08.050 -
Trials Jun 2009Randomised controlled trials are the best research design for decisions about the effect of different interventions but randomisation does not, of itself, promote the... (Review)
Review
Randomised controlled trials are the best research design for decisions about the effect of different interventions but randomisation does not, of itself, promote the applicability of a trial's results to situations other than the precise one in which the trial was done. While methodologists and trialists have rightly paid great attention to internal validity, much less has been given to applicability. This narrative review is aimed at those planning to conduct trials, and those aiming to use the information in them. It is intended to help the former group make their trials more widely useful and to help the latter group make more informed decisions about the wider use of existing trials. We review the differences between the design of most randomised trials (which have an explanatory attitude) and the design of trials more able to inform decision making (which have a pragmatic attitude) and discuss approaches used to assert applicability of trial results. If we want evidence from trials to be used in clinical practice and policy, trialists should make every effort to make their trial widely applicable, which means that more trials should be pragmatic in attitude.
Topics: Attitude of Health Personnel; Evidence-Based Medicine; Health Knowledge, Attitudes, Practice; Humans; Randomized Controlled Trials as Topic; Reproducibility of Results; Research Design; Treatment Outcome
PubMed: 19493350
DOI: 10.1186/1745-6215-10-37 -
Journal of Clinical Pharmacology Jul 2018The selection of appropriate endpoints in pediatric drug development trials is a critical aspect of trial design. Given the high pediatric trial failure rate, selecting...
The selection of appropriate endpoints in pediatric drug development trials is a critical aspect of trial design. Given the high pediatric trial failure rate, selecting optimal trial design elements, such as the primary efficacy endpoint, is essential to ensuring increased potential for trial success. The objectives of this study were to identify the primary efficacy endpoints measured in pediatric drug development trials submitted to the US Food and Drug Administration and to relate endpoint attributes to trial and label outcome. The analysis included pediatric pivotal efficacy studies submitted from September 2007 to July 2016 for which there was a corresponding adult trial for the same indication. Two hundred and thirty-four efficacy trials on 138 unique products studied in pediatric patients were assessed. The adult and pediatric endpoints were the same in 141 of the 234 trials (60.3%), and these trials succeeded in meeting their primary endpoint more often (122 of 141 [86.5%]) than when the adult and pediatric endpoints differed (57 of 93 [61.3%]; odds ratio, 4.03; 95%CI, 2.10-7.80). Trials that included both pediatric and adult patients succeeded more frequently than those trials that did not combine pediatric and adult patients (85 of 95 versus 94 of 139, respectively; odds ratio, 4.05; 95%CI, 1.94-9.31). No differences were observed in pediatric trial success between those using subjective and objective endpoints. Using the same endpoint in the pediatric trial as was measured in the corresponding adult trial and enrolling pediatric and adult patients in the same trial were attributes associated with trial success.
Topics: Adult; Child; Clinical Trials as Topic; Drug Development; Endpoint Determination; Humans; Pediatrics; Treatment Outcome; United States; United States Food and Drug Administration
PubMed: 29663424
DOI: 10.1002/jcph.1109 -
Kidney International Nov 2008Chronic kidney disease is assuming epidemic proportions, and an increasing number of clinical trials are testing treatments developed to improve morbidity and mortality.... (Review)
Review
Chronic kidney disease is assuming epidemic proportions, and an increasing number of clinical trials are testing treatments developed to improve morbidity and mortality. Surprisingly, however, a large proportion of these trials have had negative or neutral results. When trials unexpectedly demonstrate either no benefit or a detrimental impact of a treatment, especially when that treatment is already used in practice, critics commonly argue that the results were dictated by flawed trial design rather than the intrinsic properties of the treatment. In kidney disease therapeutics, trials commonly rely on observational data and test the hypothesis that these associations may be extrapolated to cause-and-effect. Other key issues in trial design that may affect outcomes include the impact of enrolling relatively healthier subjects, the complexity of recruiting participants with specific characteristics while maintaining generalizability, and the subtleties of event adjudication and quality of life assessments. In this article, general principles of trial design will be discussed and the potential lessons learned from recent trials in nephrology will be critically reviewed.
Topics: Chronic Disease; Clinical Protocols; Clinical Trials as Topic; Humans; Kidney Diseases; Patient Selection; Treatment Outcome
PubMed: 18563051
DOI: 10.1038/ki.2008.286 -
Trials Aug 2023Arts therapies are widely but inconsistently provided in community mental health. Whilst they are appealing to patients, evidence for their effectiveness is mixed....
Effectiveness of group arts therapies (art therapy, dance movement therapy and music therapy) compared to group counselling for diagnostically heterogeneous psychiatric community patients: study protocol for a randomised controlled trial in mental health services (the ERA study).
BACKGROUND
Arts therapies are widely but inconsistently provided in community mental health. Whilst they are appealing to patients, evidence for their effectiveness is mixed. Trials to date have been limited to one art-form or diagnosis. Patients may hold strong preferences for or against an art-form whilst group therapies rely on heterogeneity to provide a range of learning experiences. This study will test whether manualised group arts therapies (art therapy, dance movement therapy and music therapy) are effective in reducing psychological distress for diagnostically heterogeneous patients in community mental health compared to active group counselling control.
METHODS
A pragmatic multi-centre 2-arm randomised controlled superiority trial with health economic evaluation and nested process evaluation. Adults aged ≥ 18, living in the community with a primary diagnosis of psychosis, mood, or anxiety disorder will be invited to participate and provide written informed consent. Participants are eligible if they score ≥ 1.65 on the Global Severity Index of the Brief Symptom Inventory. Those eligible will view videos of arts therapies and be asked for their preference. Participants are randomised to either their preferred type of group arts therapy or counselling. Groups will run twice per week in a community venue for 20 weeks. Our primary outcome is symptom distress at the end of intervention. Secondary outcomes include observer-rated symptoms, social situation and quality of life. Data will be collected at baseline, post-intervention and 6 and 12 months post-intervention. Outcome assessors and trial statisticians will be blinded. Analysis will be intention-to-treat. Economic evaluation will assess the cost-effectiveness of group arts therapies. A nested process evaluation will consist of treatment fidelity analysis, exploratory analysis of group process measures and qualitative interviews with participants and therapists.
DISCUSSION
This will be the first trial to account for patient preferences and diagnostic heterogeneity in group arts therapies. As with all group therapies, there are a number of logistical challenges to which we have had to further adapt due to the COVID-19 pandemic. Overall, the study will provide evidence as to whether there is an additive benefit or not to the use of the arts in group therapy in community mental health care.
TRIAL REGISTRATION
ISRCTN, ISRCTN88805048 . Registered on 12 September 2018.
Topics: Adult; Humans; Art Therapy; Counseling; COVID-19; Dance Therapy; Mental Health Services; Multicenter Studies as Topic; Music Therapy; Pandemics; Quality of Life; Randomized Controlled Trials as Topic; Adolescent; Pragmatic Clinical Trials as Topic; Equivalence Trials as Topic
PubMed: 37626418
DOI: 10.1186/s13063-023-07232-0 -
Neurology Nov 2013Neurofibromatosis (NF) is a genetic disease with multiple clinical manifestations that can significantly impact quality of life (QOL). Clinical trials should include... (Review)
Review
OBJECTIVES
Neurofibromatosis (NF) is a genetic disease with multiple clinical manifestations that can significantly impact quality of life (QOL). Clinical trials should include patient-reported outcomes (PROs) as endpoints to assess treatment effects on various aspects of QOL, but there is no consensus on the selection and use of such measures in NF. This article describes the PRO Working Group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) Collaboration, its main goals, methods for identifying appropriate PRO measures for NF clinical trials, and recommendations for assessing pain intensity.
METHODS
The REiNS PRO group selected core endpoint domains important to assess in NF. The members developed criteria to rate PRO measures, including patient characteristics, psychometric properties, and feasibility, and utilized a systematic process to evaluate PROs for NF clinical trials. Within the subdomain of pain intensity, the group reviewed the Numerical Rating Scale-11 (NRS-11), the Visual Analogue Scale, and the Faces Pain Scale-Revised using this process.
RESULTS
Based on the review criteria, each of these pain intensity scales is brief, reliable, valid, and widely used. However, the NRS-11 was given the highest rating for use in NF clinical trials due to recommendations from pain experts and other consensus groups, its extensive use in research, strong psychometric data including sensitivity to change, and excellent feasibility in ages ≥ 8 years.
CONCLUSIONS
The systematic review criteria and process are effective for identifying appropriate PRO measures and provide information utilized by the REiNS Collaboration to achieve consensus regarding PROs in NF clinical trials.
Topics: Clinical Trials as Topic; Consensus; Humans; Neurilemmoma; Neurofibromatoses; Pain Measurement; Patient Outcome Assessment; Skin Neoplasms
PubMed: 24249806
DOI: 10.1212/01.wnl.0000435747.02780.bf -
Pediatrics Jun 2014There has been an overall improvement in survival rates for persons with cancer over the past 35 years. However, these gains are less prevalent among adolescents with... (Review)
Review
BACKGROUND
There has been an overall improvement in survival rates for persons with cancer over the past 35 years. However, these gains are less prevalent among adolescents with cancer aged 15 to 19 years, which may be due to lower clinical trial enrollment among adolescents with cancer.
METHODS
We conducted a literature review to assess current research regarding clinical trial enrollment and subsequent outcomes among adolescents with cancer. The search included English-language publications that reported original data from January 1985 to October 2011.
RESULTS
The search identified 539 records. Of these 539 records, there were 30 relevant original research articles. Multiple studies reported that adolescents with cancer are enrolled in clinical trials at lower rates compared with younger children and older adults. Treatment setting, physician type, and institution type may all be factors in the low enrollment rate among adolescents. Few data focused solely on adolescents, with many studies combining adolescents with young adults. The number of available studies related to this topic was limited, with significant variability in study design, methods, and outcomes.
CONCLUSIONS
This literature review suggests that adolescents with cancer are not treated at optimal settings and are enrolled in clinical trials at low rates. This may lead to inferior treatment and poor subsequent medical and psychosocial outcomes. The scarcity in data further validates the need for additional research focusing on this population.
Topics: Adolescent; Clinical Trials as Topic; Humans; Neoplasms; Patient Selection; Survival Rate; Treatment Outcome; Young Adult
PubMed: 24918213
DOI: 10.1542/peds.2014-0122C -
BMC Infectious Diseases Jul 2022Sepsis is still a major public health concern and a medical emergency due to its high morbidity and mortality. Accurate and timely etiology diagnosis is crucial for...
Evaluation of droplet digital PCR rapid detection method and precise diagnosis and treatment for suspected sepsis (PROGRESS): a study protocol for a multi-center pragmatic randomized controlled trial.
BACKGROUND
Sepsis is still a major public health concern and a medical emergency due to its high morbidity and mortality. Accurate and timely etiology diagnosis is crucial for sepsis management. As an emerging rapid and sensitive pathogen detection tool, digital droplet PCR (ddPCR) has shown promising potential in rapid identification of pathogens and antimicrobial resistance genes. However, the diagnostic value and clinical impact of ddPCR tests remains to be studied in patients with suspected sepsis. PROGRESS trial is aimed to evaluate the clinical effectiveness of a novel ddPCR assay compared with standard practice.
METHODS
PROGRESS is a multicenter, open-label, pragmatic randomized controlled trial (pRCT) set in ten hospitals, including departments of infectious disease and intensive care units. In this study, a total of 2292 patients with suspected sepsis will be randomly assigned to two arms: the ddPCR group and the control group with a ratio of 3:1. The primary outcome is the diagnostic efficacy, that is, the sensitivity and specificity of the ddPCR assay compared with the synchronous blood culture. Secondary outcomes include the mortality rates and the mean Sequential Organ Failure Assessment (SOFA) score at follow-up time points, the length of stay in the hospital, the time to directed antimicrobial therapy, duration of broad-spectrum antibiotic use, and the EQ-5D-5L score on day 90.
DISCUSSION
It is the first multicenter pragmatic RCT to explore the diagnostic efficacy and clinical impact of the ddPCR assay in patients with suspected sepsis, taking advantage of both RCT's ability to establish causality and the feasibility of pragmatic approaches in real-world studies (RWS). This trial will help us to get a comprehensive view of the assay's capacity for precise diagnosis and treatment of sepsis. It has the potential to monitor the pathogen load change and to guide the antimicrobial therapy, making a beneficial impact on the prognosis of sepsis patients.
TRIAL REGISTRATION
ClinicalTrial.gov, NCT05190861. Registered January 13, 2022-'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT05190861 .
Topics: Humans; Multicenter Studies as Topic; Organ Dysfunction Scores; Polymerase Chain Reaction; Pragmatic Clinical Trials as Topic; Prognosis; Randomized Controlled Trials as Topic; Sepsis; Treatment Outcome
PubMed: 35854212
DOI: 10.1186/s12879-022-07557-2 -
Annali Dell'Istituto Superiore Di Sanita 2011Neurodegenerative diseases are disabling conditions continuously increasing due to aging of population. A disease modifying therapy that slows or stops disease... (Review)
Review
Neurodegenerative diseases are disabling conditions continuously increasing due to aging of population. A disease modifying therapy that slows or stops disease progression is therefore a major unmet medical need. Unfortunately, research for effective treatments is hampered by lack of knowledge on the pathologic processes underpinning these diseases and of reliable biomarkers. Clinical trials are difficult, as they require large populations that need to be followed for very long periods to capture possible effects on disease progression. These difficulties produce frequent failures and waste of human and economic resources. Since research has to continue in this area, until comprehensive knowledge of basic pathologic processes is obtained, alternative study designs can be considered to identify disease modifiers and to reduce costs of clinical studies.
Topics: Clinical Trials as Topic; Cost-Benefit Analysis; Humans; Neurodegenerative Diseases; Research Design; Treatment Outcome
PubMed: 21430339
DOI: 10.4415/ANN_11_01_11 -
Annals of Oncology : Official Journal... Oct 2015
Topics: Academies and Institutes; Clinical Trials as Topic; Humans; Neoplasms; Research Design; State Medicine
PubMed: 26240217
DOI: 10.1093/annonc/mdv332