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Journal of B.U.ON. : Official Journal... Dec 2018In oncology clinical trials, many different endpoints can be used as primary or secondary endpoints. Advances in cancer treatment have provided longer survival outcomes,... (Review)
Review
In oncology clinical trials, many different endpoints can be used as primary or secondary endpoints. Advances in cancer treatment have provided longer survival outcomes, particularly in certain types of cancer. Overall survival is accepted as the gold standard endpoint for demonstrating clinical benefit; however, it is associated with some disadvantages such as requirement of long-term follow-up, requirement of higher number of patients, and high cost. Thus, the question "what is the most appropriate endpoint in clinical trials?" comes to mind. The present review discusses the endpoints in oncology clinical trials.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Disease-Free Survival; Humans; Neoplasms; Quality of Life; Survival Rate
PubMed: 30722104
DOI: No ID Found -
Clinical Gastroenterology and... May 2007The choice of primary endpoint for a clinical trial is one of the most important determinants of the ability of a clinical trial to demonstrate efficacy of therapeutic... (Review)
Review
The choice of primary endpoint for a clinical trial is one of the most important determinants of the ability of a clinical trial to demonstrate efficacy of therapeutic agents. Although there are still no clear, universally accepted guidelines on the definition of clinical benefit for irritable bowel syndrome (IBS), consensus guidelines stress the importance of using validated endpoints. This article reviews the evidence available in the literature on the psychometric validation and performance of the 3 endpoints recommended by the Rome III Committee for use as primary endpoints in treatment trials of IBS. The Rome III Committee recommends 2 types of measures: binary endpoints addressing the construct of relief (that is, adequate relief and satisfactory relief) and an integrative symptom questionnaire that addresses the change in severity of a representative group of symptoms of IBS (that is, the IBS Severity Scale). The current evidence suggests that at present, adequate relief should be recognized by regulatory authorities as an acceptable primary endpoint in clinical trials. This analysis also suggests that data from individual clinical trials should be pooled and undergo meta-analysis, and that prospective studies should be considered to further characterize the performance of available endpoints as outcome measures in pharmacotherapeutic trials in IBS.
Topics: Clinical Trials as Topic; Humans; Irritable Bowel Syndrome; Outcome Assessment, Health Care; Practice Guidelines as Topic; Research Design
PubMed: 17428741
DOI: 10.1016/j.cgh.2007.03.004 -
The Journal of Headache and Pain Sep 2018Primary headache are prevalent and debilitating disorders. Acute pain cessation is one of the key points in their treatment. Many drugs have been studied but the design... (Review)
Review
BACKGROUND
Primary headache are prevalent and debilitating disorders. Acute pain cessation is one of the key points in their treatment. Many drugs have been studied but the design of the trials is not usually homogeneous. Efficacy of the trial is determined depending on the selected primary endpoint and usually other different outcomes are measured. We aim to critically appraise which were the employed outcomes through a systematic review.
METHODS
We conducted a systematic review of literature focusing on studies on primary headache evaluating acute relief of pain, following the PRISMA guideline. The study population included patients participating in a controlled study about symptomatic treatment. The comparator could be placebo or the standard of care. The collected information was the primary outcome of the study and all secondary outcomes. We evaluated the studied drug, the year of publication and the type of journal. We performed a search and we screened all the potential papers and reviewed them considering inclusion/exclusion criteria.
RESULTS
The search showed 4288 clinical trials that were screened and 794 full articles were assessed for eligibility for a final inclusion of 495 papers. The studies were published in headache specific journals (58%), general journals (21.6%) and neuroscience journals (20.4%). Migraine was the most studied headache, in 87.8% studies, followed by tension type headache in 4.7%. Regarding the most evaluated drug, triptans represented 68.6% of all studies, followed by non-steroidal anti-inflammatories (25.1%). Only 4.6% of the papers evaluated ergots and 1.6% analyzed opioids. The most frequent primary endpoint was the relief of the headache at a determinate moment, in 54.1%. Primary endpoint was evaluated at 2-h in 69.9% of the studies. Concerning other endpoints, tolerance was the most frequently addressed (83%), followed by headache relief (71.1%), improvement of other symptoms (62.5%) and presence of relapse (54%). The number of secondary endpoints increased from 4.2 (SD = 2.0) before 1991 to 6.39 after 2013 (p = 0.001).
CONCLUSION
Headache relief has been the most employed primary endpoint but headache disappearance starts to be firmly considered. The number of secondary endpoints increases over time and other outcomes such as disability, quality of life and patients' preference are receiving attention.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Disabled Persons; Headache Disorders, Primary; Humans; Patient Compliance; Practice Guidelines as Topic; Quality of Life; Treatment Outcome; Tryptamines
PubMed: 30242571
DOI: 10.1186/s10194-018-0920-9 -
The European Respiratory Journal Sep 2013Clinical trials for the treatment of cystic fibrosis (CF) lung disease are important to test and optimise new therapeutic interventions. To evaluate the effect of these... (Review)
Review
Clinical trials for the treatment of cystic fibrosis (CF) lung disease are important to test and optimise new therapeutic interventions. To evaluate the effect of these interventions, sensitive and accurate outcome measures are needed. The most commonly used endpoints are spirometric variables such as the forced expiratory volume in 1 s and respiratory tract exacerbations. Unfortunately, these endpoints are relatively insensitive for monitoring progression of CF lung disease, and thus require a large number of patients when used in clinical studies. In addition, these endpoints are not suitable to study CF lung disease in young children. Chest computed tomography (CT) holds great promise for use as a sensitive surrogate endpoint in CF. A large body of evidence has been produced to validate the use of chest CT as a primary endpoint to study CF lung disease. However, before chest CT can be used in clinical trials, it has to be recognised as a validated surrogate endpoint by regulatory agencies. The aim of this review is to summarise what is currently known about the use of chest CT as surrogate endpoint in clinical trials in CF.
Topics: Clinical Trials as Topic; Cystic Fibrosis; Disease Progression; Humans; Image Processing, Computer-Assisted; Lung; Quality of Life; Reproducibility of Results; Sensitivity and Specificity; Spirometry; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 23258780
DOI: 10.1183/09031936.00051512 -
World Journal of Surgery Jun 2014Few randomized controlled trials (RCTs) have been performed in patients undergoing pancreaticoduodenectomy (PD). An important factor contributing to this is the large... (Review)
Review
BACKGROUND
Few randomized controlled trials (RCTs) have been performed in patients undergoing pancreaticoduodenectomy (PD). An important factor contributing to this is the large number of patients needed to adequately power RCTs for relevant clinical single endpoints. A PD-specific composite endpoint (CEP) could solve this problem. The aim of the present study was to develop a PD-specific CEP, consisting of complications related to PD, allowing reduction in sample sizes and improving the ability to compare outcomes.
METHODS
PD-specific CEP components were selected after a systematic review of the literature and consensus between 25 international pancreatic surgeons. Ultimately, prospective cohorts of patients who underwent PD in two high-volume HPB centers (London, UK, and Maastricht, NL) were used to assess the event rate and effect of implementing a PD-specific CEP.
RESULTS
From a total of 18 single-component endpoints, intra-abdominal abscess, sepsis, post-PD hemorrhage, bile leakage, gastrojejunostomy leakage, leakage of the pancreatic anastomosis, delayed gastric emptying, and operative mortality within 90 days were selected to be included the PD-specific CEP. All eight components had consensus definitions and a Dindo-Clavien classification of 3 or more. The incidence of the PD-specific CEP was 24.7 % in the Maastricht cohort and 23.3 % in the London cohort. These incidence rates led to a twofold reduction in the theoretical calculated sample size for an adequately powered RCT on PD using this CEP as a primary endpoint.
CONCLUSIONS
The proposed PD-specific CEP enables clinical investigators to adequately power RCTs on PD and increases the feasibility, comparability, and utility in meta-analysis.
Topics: Aged; Endpoint Determination; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Pancreaticoduodenectomy; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; United Kingdom
PubMed: 24366279
DOI: 10.1007/s00268-013-2421-y -
Critical Reviews in Oncology/hematology Dec 2019Spin, the misrepresentation of research findings, in clinical trial abstract has been shown to influence how oncologist rate a drug's efficacy. (Review)
Review
PURPOSE
Spin, the misrepresentation of research findings, in clinical trial abstract has been shown to influence how oncologist rate a drug's efficacy.
MATERIALS AND METHODS
We searched PubMed for clinical trials published in ten key journals in 2017. Our primary objectives were to assess the frequency and manifestations of spin in the abstracts of those clinical trials that measured both overall survival and at least one surrogate efficacy endpoints.
RESULTS
124 trials were included for analysis. We found evidence of spin in 46 of 124 (37.1%, 95% CI 29.1%-45.9%) trial abstracts. Spin in the abstract results was most often due to authors emphasizing a statistically significant subgroup analysis (n = 6). Spin in the abstract conclusions was most often due to authors relying on a statistically significant surrogate endpoint to highlight the bioefficacy of the intervention (n = 17).
CONCLUSION
Spin is prevalent in the abstracts of oncology clinical trials that measure OS and a surrogate endpoint. The conclusion sections of abstracts were most prone to contain spin. When OS was the primary endpoint, spin was primarily used to distract from the nonsignificant OS data. To mitigate unintentional hype for cancer therapies, we recommend authors structure their conclusions around patient-important outcomes.
Topics: Clinical Trials as Topic; Humans; Medical Oncology; Neoplasms
PubMed: 31733444
DOI: 10.1016/j.critrevonc.2019.102821 -
Statistics in Medicine Dec 2019Interim analyses are routinely used to monitor accumulating data in clinical trials. When the objective of the interim analysis is to stop the trial if the trial is...
Interim analyses are routinely used to monitor accumulating data in clinical trials. When the objective of the interim analysis is to stop the trial if the trial is deemed futile, it must ideally be conducted as early as possible. In trials where the clinical endpoint of interest is only observed after a long follow-up, many enrolled patients may therefore have no information on the primary endpoint available at the time of the interim analysis. To facilitate earlier decision-making, one may incorporate early response data that are predictive for the primary endpoint (eg, an assessment of the primary endpoint at an earlier time) in the interim analysis. Most attention so far has been given to the development of interim test statistics that include such short-term endpoints, but not to decision procedures. Existing tests moreover perform poorly when the information is scarce, eg, due to rare events, when the cohort of patients with observed primary endpoint data is small, or when the short-term endpoint is a strong but imperfect predictor. In view of this, we develop an interim decision procedure based on the conditional power approach that utilizes the short-term and long-term binary endpoints in a framework that is expected to provide reliable inferences, even when the primary endpoint is only available for a few patients, and has the added advantage that it allows the use of historical information. The operational characteristics of the proposed procedure are evaluated for the phase III clinical trial that motivated this approach, using simulation studies.
Topics: Biostatistics; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Computer Simulation; Decision Making; Early Termination of Clinical Trials; Endpoint Determination; Humans; Models, Statistical
PubMed: 31631357
DOI: 10.1002/sim.8366 -
Expert Opinion on Biological Therapy Feb 2020: Therapeutic goals in inflammatory bowel diseases (IBD) have evolved, over the last decades, from clinical response to complete remission (clinical and endoscopic... (Review)
Review
: Therapeutic goals in inflammatory bowel diseases (IBD) have evolved, over the last decades, from clinical response to complete remission (clinical and endoscopic remission).: Development of biologics and small molecules has been associated with the development of new endpoints in IBD trials that could not have been achieved in the pre-biologics era. Herein, we focus on evolving endpoints for approved biologics and small molecules. We searched for relevant publications using Medline/PubMed, Embase and the Cochrane Library from their inception to 1 July 2019.: Endpoints differ between induction (clinical and endoscopic response) and maintenance trials (clinical and endoscopic remission) because the goal is to evaluate the anti-inflammatory effect of a given drug during induction, whereas full disease control is the ultimate goal during the maintenance phase in order to change patients' life and disease course. Histological healing has recently emerged as a new co-primary endpoint in ulcerative colitis, and is now part of the definition of mucosal healing in these trials. Whether new endpoints such as transmural and radiologic healing could become an endpoint and replace endoscopy in Crohn's disease trials in the near future requires further investigation.
Topics: Biological Products; Biomarkers; Colitis, Ulcerative; Crohn Disease; Drug Approval; Endpoint Determination; History, 20th Century; History, 21st Century; Humans; Inflammatory Bowel Diseases; Libraries; Randomized Controlled Trials as Topic; Small Molecule Libraries; Wound Healing
PubMed: 31815548
DOI: 10.1080/14712598.2020.1702020 -
European Heart Journal Jan 2006Many trials have been conducted to assess the efficacy of various strategies in the prevention of venous thrombo-embolism (VTE). Some of these trials have been subject... (Review)
Review
AIMS
Many trials have been conducted to assess the efficacy of various strategies in the prevention of venous thrombo-embolism (VTE). Some of these trials have been subject to methodological criticisms. We aimed to assess the methodological issues raised by VTE trials.
METHODS AND RESULTS
We searched MEDLINE and the Cochrane Central Register of Controlled Trials for articles assessing primary thromboprophylaxis published between 1994 and 2003 in 60 general medical and specialty journals. A total of 77 articles were analysed by two independent reviewers using a list of items. No primary endpoint was defined in 20% of trials. Although the primary endpoint was collected before day 15 in 75% of trials, there were >/=20% missing data in 56% of articles and >/=30% in 24.2% of articles. The rate of missing data was 23.7+/-9.7% in studies using venography-detected deep-vein thrombosis as an endpoint compared with 5.6+/-6.0% in studies using other endpoints. Among the 47 superiority trials, 27 (57.4%) reported an intention-to-treat (ITT) analysis, but only 10 (21.3%) reported an analysis that complied with this principle. These results were consistent when limiting the analysis to articles published in high-impact journal (impact factor more than 5).
CONCLUSION
Recent randomized controlled trials assessing prophylactic regimens in VTE have important methodological limitations in terms of primary endpoints, missing data, and compliance with the ITT principle. These methodological shortcomings should be addressed when planning future trials.
Topics: Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Risk Factors; Thromboembolism; Treatment Outcome; Venous Thrombosis
PubMed: 16223743
DOI: 10.1093/eurheartj/ehi587