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Regional Anesthesia and Pain Medicine 2011The past century has seen immense progress in the advancement of methodology to evaluate efficacy of treatment interventions for acute and chronic pain. Continuing... (Review)
Review
The past century has seen immense progress in the advancement of methodology to evaluate efficacy of treatment interventions for acute and chronic pain. Continuing challenges revolve around how to best select and measure primary efficacy outcomes for a given analgesic trial. Recognizing the complex, multidimensional, sensory and emotional nature of pain and applying psychometric techniques have facilitated the development of several valid and reliable self-report measures that evaluate pain intensity, pain relief, and other important outcome domains relevant to pain treatment. In the setting of emerging new pain treatment strategies, careful consideration must be given to match current or novel outcome measures to the specific goals of a proposed trial. Future research is needed to directly compare current methods with newer measurement approaches for the critical goal of maximizing validity, reliability, and utility of different outcome measures in clinical trials of pain treatment.
Topics: Animals; Clinical Trials as Topic; Humans; Pain; Pain Management; Pain Measurement; Self Report; Treatment Outcome
PubMed: 21610560
DOI: 10.1097/AAP.0b013e318217a635 -
Fertility and Sterility Nov 2008This Educational Bulletin provides background and tips on how to recognize quality trials and then focuses on evaluating the validity, importance, and relevance of... (Review)
Review
This Educational Bulletin provides background and tips on how to recognize quality trials and then focuses on evaluating the validity, importance, and relevance of clinical trial results.
Topics: Bias; Clinical Trials as Topic; Data Interpretation, Statistical; Female; Humans; Male; Patient Selection; Pregnancy; Random Allocation; Reproducibility of Results; Research Design; Treatment Outcome
PubMed: 19007606
DOI: 10.1016/j.fertnstert.2008.08.037 -
Giornale Italiano Di Cardiologia (2006) Nov 2019Early interruption of a clinical trial is not a rare case, and it may be due to several reasons that are summarized in the present article. It is important for the... (Review)
Review
Early interruption of a clinical trial is not a rare case, and it may be due to several reasons that are summarized in the present article. It is important for the clinician, the primary user of the information derived from clinical trials, to be able to assess whether the eventual interruption of the trial had been planned in the study protocol, whether the study organization was such as to correctly monitor the accrual of efficacy and safety data, who took the decision to interrupt the trial, whether the study patients have been exposed to excessive risks and, finally, whether the conclusions of the study report are valid. In most cases, these issues are carefully assessed during the review process of the study publication (and, of course, by the regulatory authorities) but, particularly for the studies interrupted for "overwhelming evidence of benefit", wisdom and prudence are mandatory, and the results must be considered within the context of all available evidence.
Topics: Clinical Trials as Topic; Early Termination of Clinical Trials; Humans; Research Design
PubMed: 31697268
DOI: 10.1714/3254.32222 -
Contemporary Clinical Trials Jun 2021Modern data analysis tools and statistical modeling techniques are increasingly used in clinical research to improve diagnosis, estimate disease progression and predict... (Review)
Review
Opportunity for efficiency in clinical development: An overview of adaptive clinical trial designs and innovative machine learning tools, with examples from the cardiovascular field.
Modern data analysis tools and statistical modeling techniques are increasingly used in clinical research to improve diagnosis, estimate disease progression and predict treatment outcomes. What seems less emphasized is the importance of the study design, which can have a serious impact on the study cost, time and statistical efficiency. This paper provides an overview of different types of adaptive designs in clinical trials and their applications to cardiovascular trials. We highlight recent proliferation of work on adaptive designs over the past two decades, including some recent regulatory guidelines on complex trial designs and master protocols. We also describe the increasing role of machine learning and use of metaheuristics to construct increasingly complex adaptive designs or to identify interesting features for improved predictions and classifications.
Topics: Adaptive Clinical Trials as Topic; Clinical Trials as Topic; Humans; Machine Learning; Models, Statistical; Research Design; Treatment Outcome
PubMed: 33845209
DOI: 10.1016/j.cct.2021.106397 -
Clinical Cancer Research : An Official... May 2021Restrictive eligibility criteria induce differences between clinical trial and "real-world" treatment populations. Restrictions based on prior therapies are common;...
PURPOSE
Restrictive eligibility criteria induce differences between clinical trial and "real-world" treatment populations. Restrictions based on prior therapies are common; minimizing them when appropriate may increase patient participation in clinical trials.
EXPERIMENTAL DESIGN
A multi-stakeholder working group developed a conceptual framework to guide evaluation of prevailing practices with respect to using prior treatment as selection criteria for clinical trials. The working group made recommendations to minimize restrictions based on prior therapies within the boundaries of scientific validity, patient centeredness, distributive justice, and beneficence.
RECOMMENDATIONS
(i) Patients are eligible for clinical trials regardless of the number or type of prior therapies and without requiring a specific therapy prior to enrollment unless a scientific or clinically based rationale is provided as justification. (ii) Prior therapy (either limits on number and type of prior therapies or requirements for specific therapies before enrollment) could be used to determine eligibility in the following cases: a) the agents being studied target a specific mechanism or pathway that could potentially interact with a prior therapy; b) the study design requires that all patients begin protocol-specified treatment at the same point in the disease trajectory; and c) in randomized clinical studies, if the therapy in the control arm is not appropriate for the patient due to previous therapies received. (iii) Trial designers should consider conducting evaluation separately from the primary endpoint analysis for participants who have received prior therapies.
CONCLUSIONS
Clinical trial sponsors and regulators should thoughtfully reexamine the use of prior therapy exposure as selection criteria to maximize clinical trial participation..
Topics: Biomedical Research; Clinical Decision-Making; Clinical Trials as Topic; Disease Management; Humans; Medical Oncology; Research Design
PubMed: 33563637
DOI: 10.1158/1078-0432.CCR-20-3854 -
Expert Review of Clinical Pharmacology Oct 2017despite methodological advances in epilepsy clinical trials, the proportion of patients reaching seizure-freedom has not substantially changed over the years. We review... (Review)
Review
despite methodological advances in epilepsy clinical trials, the proportion of patients reaching seizure-freedom has not substantially changed over the years. We review the main methodological limitations of current trials, the possible strategies to overcome these limits, and the issues that need to be addressed in next future. Area covered: references were identified by PubMed search until March 2017 and unpublished literature was searched on ClinicalTrials.gov. Add-on trials mainly involve refractory epilepsy subjects, reducing overall response to the investigational drug. The inclusion of subjects with earlier disease from less developed countries has partially allowed overcoming this limitation, but has introduced more random variability of results. Monotherapy trials rise methodological, economical, and ethical concerns with different regulatory requirements in European Union and in the United States of America. Newer trial designs, such as futility trials or 'time-to-event' design, have been implemented. Moreover, both add-on and monotherapy trials results might be affected by patient's ability to recognize and record seizures, and by randomness of seizures occurrence over time. Possible strategies to achieve more reliable outcomes are detailed. Expert commentary: clinical trial methodology needs to be optimized to better address regulatory agencies requirements and to encounter both patients' and clinicians' needs.
Topics: Anticonvulsants; Clinical Trials as Topic; Developing Countries; Epilepsy; Humans; Patient Selection; Research Design; Time Factors; Treatment Outcome
PubMed: 28715945
DOI: 10.1080/17512433.2017.1356720 -
Cancer Investigation Oct 2021The global burden of cancer is estimated to be more than 20 million cases by 2030, the majority occurring in low- and middle- income countries (LMICs). LMICs account for...
The global burden of cancer is estimated to be more than 20 million cases by 2030, the majority occurring in low- and middle- income countries (LMICs). LMICs account for 64% of global cancer deaths and 80% of disability-adjusted-life-years lost. Despite this, only 5% of the global cancer resources are spent in LMICs causing a high mortality-to-income ratio. Despite the burgeoning number of clinical trials in the HICs, there are several reasons to conduct clinical trials in LMICs. In this commentary, we discuss the problem of access to clinical trials in LMICs using India as a case study.
Topics: Clinical Trials as Topic; Cost of Illness; Developing Countries; Early Detection of Cancer; Humans; India; Neoplasms; Registries
PubMed: 33818233
DOI: 10.1080/07357907.2021.1912078 -
Schweizerische Medizinische... Oct 1999The article describes the evolution of high frequency oscillation since its first use by Lunkenheimer through the initial failed NIH trial and subsequent more successful... (Review)
Review
The article describes the evolution of high frequency oscillation since its first use by Lunkenheimer through the initial failed NIH trial and subsequent more successful trials to its current widespread use in the neonatal population. The importance of oscillating at an optimal lung volume, achieved through a volume recruitment manoeuvre, is emphasised as is the efficacy with which oscillation clears CO2. The lack of adequate control of these two factors in the initial NIH trial is suggested as a possible cause of the trial's failure. Comment is made on optimising oscillator settings as well on elementary mechanics of high frequency oscillation and the effect of high frequency oscillation on surfactant degradation. Given the difficulty of recruiting lung volume in late RDS, a suggestion is made to combine high frequency oscillation with perfluorocarbon. The former as a mechanism for maintaining lung volume which has been recruited by the perfluorocarbon. The authors speculate that the use of high frequency oscillation will increase in both the paediatric and adult population.
Topics: Adult; Child; Clinical Trials as Topic; High-Frequency Ventilation; Humans; Infant, Newborn; Lung Volume Measurements; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
PubMed: 10582261
DOI: No ID Found -
Lancet (London, England) Jul 1984
Clinical Trial
Topics: Clinical Trials as Topic; Female; Humans; Pregnancy; Pregnancy Complications; Ultrasonography
PubMed: 6146755
DOI: No ID Found -
European Neurology 1999Regulatory authorities favour the use of clinical endpoints, over surrogate endpoints, to demonstrate the efficacy of therapeutic agents for diabetic peripheral... (Review)
Review
Regulatory authorities favour the use of clinical endpoints, over surrogate endpoints, to demonstrate the efficacy of therapeutic agents for diabetic peripheral neuropathy (DPN). Progress in the quantification of the severity of DPN has been observed in recent years. The NIS-LL (Neuropathy Impairment Score in the Lower Limbs) is a new scale which quantifies the neurological function in DPN. This scale for determining the neuropathy impairment in DPN optimises the chances of demonstrating clinical change following pharmaceutical intervention in patients with early-stage neuropathy. The use of the NIS-LL in clinical trials, together with other tests measuring nerve function, pain and risk of foot ulcer, provides the best opportunity to evaluate the efficacy of new therapeutic agents for the treatment of DPN.
Topics: Aged; Canada; Clinical Trials as Topic; Diabetic Neuropathies; Humans; Middle Aged; Muscle, Skeletal; Neural Conduction; Neurologic Examination; Peripheral Nervous System Diseases; Reflex; Reproducibility of Results; Severity of Illness Index
PubMed: 10023123
DOI: 10.1159/000052074