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Journal of Biopharmaceutical Statistics 2019In diagnostic device evaluation, it is important to have an integrated benefit-risk (BR) assessment for safety and effectiveness, which is not same as the assessment for...
In diagnostic device evaluation, it is important to have an integrated benefit-risk (BR) assessment for safety and effectiveness, which is not same as the assessment for drugs and therapeutic devices. Correct diagnosis does not lead to direct clinical outcome such as longer survival, release of symptoms, tumor shrinkage, etc.; but leads to the proper treatment in time while incorrect diagnosis may result in serious consequences of unnecessary tests and wrong treatments. Some common measures used in evaluating the accuracy of a diagnostic device include sensitivity, specificity, positive predictive value and negative predictive value. Here, we propose a BR measure by incorporating information about true-positive and true-negative cases (correct diagnosis) and false-positive and false-negative cases (incorrect diagnosis) for facilitating the necessary decision-making. Three decision rules are discussed depending on the purpose of the clinical study. Different statistical models are developed for estimating the BR measure for data obtained from different sampling schemes (cross-sectional and case-control sampling). The construction of confidence intervals (CIs) for the proposed BR measure is based on (i) the asymptotic normality of the maximum likelihood estimators (MLEs), and (ii) parametric bootstrap re-sampling technique. The performance of these CIs is evaluated by intensive Monte-Carlo simulations which reveal that both CIs perform reasonably well. Finally, the proposed methodology is applied to two clinical trial datasets.
Topics: Case-Control Studies; Clinical Trials as Topic; Diagnostic Tests, Routine; False Negative Reactions; False Positive Reactions; Female; Humans; Male; Monte Carlo Method; Pregnancy; Risk Assessment
PubMed: 31498711
DOI: 10.1080/10543406.2019.1657135 -
Oral Oncology Mar 2015Despite substantial improvements in the treatment of head and neck cancer (HNC) over the last two decades, overall survival rates remain unsatisfactory. The need for... (Review)
Review
Despite substantial improvements in the treatment of head and neck cancer (HNC) over the last two decades, overall survival rates remain unsatisfactory. The need for improved therapeutic approaches for HNC patients is hampered by low patient recruitment rates in HNC clinical trials, particularly Phase III studies. Based on an analysis of ClinicalTrials.gov, this article identified several potential barriers to patient recruitment in Phase I-III clinical trials of treatments for HNC. Of 694 HNC trials identified on ClinicalTrials.gov from multiple sites worldwide, 91 (13.1%) were identified as either terminated, suspended or withdrawn; 27.5% (n=25) of these did not provide an additional reason for stopping recruitment early. Insufficient accrual was the most common reason provided for trial closure (n=23, 25.3%). Possible reasons for the insufficient accrual rates include the inappropriate designs of these studies given the change in HNC tumour biology in the last 20years, the low incidence of the disease, and the diversity of treatment standards and referral processes across countries. Given the low numbers of drugs approved for HNC, it is important that barriers to recruitment in this field are addressed to allow new therapies to be successfully validated in completed clinical trials. This review discusses how these accrual challenges may be overcome with changes to clinical trial designs, including their adaptation to specific subgroups, such as human papillomavirus-positive patients.
Topics: Clinical Trials as Topic; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Global Health; Head and Neck Neoplasms; Humans; Patient Selection; Research Design; Treatment Failure
PubMed: 25593017
DOI: 10.1016/j.oraloncology.2014.12.007 -
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 -
Journal of the National Cancer Institute Mar 2020Historically, the gold standard for evaluation of cancer therapeutics, including medical devices, has been the randomized clinical trial. Although high-quality clinical... (Review)
Review
Historically, the gold standard for evaluation of cancer therapeutics, including medical devices, has been the randomized clinical trial. Although high-quality clinical data are essential for safe and judicious use of therapeutic oncology devices, class II devices require only preclinical data for US Food and Drug Administration approval and are often not rigorously evaluated prior to widespread uptake. Herein, we review master protocol design in medical oncology and its application to therapeutic oncology devices, using examples from radiation oncology. Unique challenges of clinical testing of radiation oncology devices (RODs) include patient and treatment heterogeneity, lack of funding for trials by industry and health-care payers, and operator dependence. To address these challenges, we propose the use of master protocols to optimize regulatory, financial, administrative, quality assurance, and statistical efficiency of trials evaluating RODs. These device-specific master protocols can be extrapolated to other devices and encompass multiple substudies with the same design, statistical considerations, logistics, and infrastructure. As a practical example, we outline our phase I and II master protocol trial of stereotactic magnetic resonance imaging-guided adaptive radiotherapy, which to the best of our knowledge is the first master protocol trial to test a ROD. Development of more efficient clinical trials is needed to promote thorough evaluation of therapeutic oncology devices, including RODs, in a resource-limited environment, allowing more practical and rapid identification of the most valuable advances in our field.
Topics: Clinical Trials as Topic; Equipment and Supplies; Humans; Magnetic Resonance Imaging; Neoplasms; Radiation Oncology; Radiotherapy, Image-Guided; Randomized Controlled Trials as Topic; Stereotaxic Techniques; United States; United States Food and Drug Administration
PubMed: 31504680
DOI: 10.1093/jnci/djz167 -
BMJ (Clinical Research Ed.) Jun 2013Calling researchers and editors to help restore invisible and abandoned trials
Calling researchers and editors to help restore invisible and abandoned trials
Topics: Biomedical Research; Clinical Trials as Topic; Early Termination of Clinical Trials; Evidence-Based Medicine; Humans; Publishing
PubMed: 23766484
DOI: 10.1136/bmj.f3601 -
Fertility and Sterility Jun 2018Personalized medicine has many definitions. This term is often used synonymously with precision medicine, which is defined as the classifying patients with a disease or... (Review)
Review
Personalized medicine has many definitions. This term is often used synonymously with precision medicine, which is defined as the classifying patients with a disease or condition based on their phenotypic findings, such as biomarkers or genomics, into subpopulations that differ in their response to a specific treatment. Personalized medicine, however, can also mean the treatment of individual patients based on many contextual factors, such as response to therapy and patient preferences, in addition to predefined phenotypic findings. Regulatory approval for the marketing of a new drug or a new indication for a marketed drug requires a positive benefit risk profile and substantial evidence of effectiveness. The indication is based on the eligibility criteria and outcomes of the clinical trial(s) underpinning the regulatory approval. For precision medicine, drugs are often developed with companion diagnostics that are necessary for selection of the subgroup of patients, in contrast to personalized medicine which may be directed at a single patient. Most drugs are approved with a fixed dosage regimen for the approved population, but some drugs and biologics are approved with instructions to tailor therapy for individual patients, whether it be dosing, combination with other therapies, or selection among a class of medications. Hence, more often than not, personalized medicine directed at individual patients is achieved through the practice of medicine rather than regulatory action.
Topics: Clinical Trials as Topic; Drug Approval; Drug Industry; Fertility Agents; Humans; Legislation, Medical; Precision Medicine; Reproductive Medicine; Reproductive Techniques, Assisted
PubMed: 29935654
DOI: 10.1016/j.fertnstert.2018.03.027 -
Pediatrics Jun 2014Despite overall improvement in survival, morbidity, and quality of life of US patients with cancer, this progress is less prevalent in the population of adolescent and... (Review)
Review
Despite overall improvement in survival, morbidity, and quality of life of US patients with cancer, this progress is less prevalent in the population of adolescent and young adult patients with cancer, including those between the ages of 15 and 19 years. Evidence suggests that participation in clinical trials is associated with better survival outcomes among children and adolescents with cancer; however, adolescents have lower clinical trial participation rates compared with younger age cohorts. To better understand the unique concerns among adolescent patients with cancer, the Division of Cancer Prevention and Control at the Centers for Disease Control and Prevention convened a workgroup of researchers and health care providers in the field of adolescent and young adult oncology and cancer survivorship to examine the barriers and challenges limiting the participation of adolescents in clinical trials and to define ways to improve upon these concerns. This article summarizes the activities of the workgroup and their suggestions for enhanced accrual.
Topics: Adolescent; Clinical Trials as Topic; Education; Humans; Neoplasms; Patient Selection; Referral and Consultation
PubMed: 24918214
DOI: 10.1542/peds.2014-0122D -
Journal of Clinical Oncology : Official... Mar 2005Current staging and risk-stratification methods in oncology, while helpful, fail to adequately predict malignancy aggressiveness and/or response to specific treatment.... (Review)
Review
Current staging and risk-stratification methods in oncology, while helpful, fail to adequately predict malignancy aggressiveness and/or response to specific treatment. Increased knowledge of cancer biology is generating promising marker candidates for more accurate diagnosis, prognosis assessment, and therapeutic targeting. To apply these exciting results to maximize patient benefit, a disciplined application of well-designed clinical trials for assessing the utility of markers should be used. In this article, we first review the major issues to consider when designing a clinical trial assessing the usefulness of a predictive marker. We then present two classes of clinical trial designs: the Marker by Treatment Interaction Design and the Marker-Based Strategy Design. In the first design, we assume that the marker splits the population into groups in which the efficacy of a particular treatment will differ. This design can be viewed as a classical randomized clinical trial with upfront stratification for the marker. In the second design, after the marker status is known, each patient is randomly assigned either to have therapy determined by their marker status or to receive therapy independent of marker status. The predictive value of the marker is assessed by comparing the outcome of all patients in the marker-based arm to that of all of the patients in the non-marker-based arm. We present detailed sample size calculations for a specific clinical scenario. We discuss the advantages and disadvantages of the two trial designs and their appropriateness to specific clinical situations to assist investigators seeking to design rigorous, marker-based clinical trials.
Topics: Biomarkers, Tumor; Clinical Trials as Topic; Humans; Neoplasms; Predictive Value of Tests; Prognosis; Research Design
PubMed: 15774793
DOI: 10.1200/JCO.2005.01.112 -
JAMA Neurology Sep 2017
Review
Topics: Alzheimer Disease; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials as Topic; Cost-Benefit Analysis; Female; Humans; Molecular Imaging; Therapies, Investigational
PubMed: 28738114
DOI: 10.1001/jamaneurol.2017.1528 -
Neurology Feb 2002Assessment of the diagnostic criteria of reflex sympathetic dystrophy (RSD) and evaluation of the impact of the introduction of the diagnostic criteria of complex... (Comparative Study)
Comparative Study Review
OBJECTIVE
Assessment of the diagnostic criteria of reflex sympathetic dystrophy (RSD) and evaluation of the impact of the introduction of the diagnostic criteria of complex regional pain syndrome (CRPS) on the international application of diagnostic criteria of RSD.
METHODS
Randomized controlled trials and clinical investigations, published between January 1980 and June 2000, were evaluated with regard to the applied diagnostic criteria of RSD.
RESULTS
One hundred seven studies were identified. Thirty-four of these studies were excluded because of inadequate reporting of diagnostic criteria. The 73 included studies were not homogeneous with regard to the diagnostic criteria because they applied many different aspects of sensory and autonomic features. Only 12% of the studies considered the presence of motor features, mostly vaguely described, as mandatory for the diagnosis RSD. Although 10 of the 23 studies published since the introduction of CRPS have applied this term, only 3 used the exact criteria without additions or other modifications.
CONCLUSION
Diagnostic criteria sets of RSD focus on many different aspects of sensory and autonomic features that generally are described vaguely. This has not changed since the introduction of the CPRS criteria. These findings question whether the current criteria adequately define RSD.
Topics: Clinical Trials as Topic; Humans; Neurologic Examination; Reflex Sympathetic Dystrophy
PubMed: 11865127
DOI: 10.1212/wnl.58.4.522