scholarly journals Analysis of responder-based endpoints: improving power through utilising continuous components

2019 ◽  
Author(s):  
James Wason ◽  
Martina McMenamin ◽  
Susanna Dodd
Keyword(s):  
Clinical Trials ◽  
Continuous Variables ◽  
Methodological Development ◽  
Continuous Component ◽  
Vast Array ◽  
Binary Method ◽  
Continuous Components ◽  
Trial Endpoints ◽  
Definition Of ◽  
Clinical Conditions

Abstract Background Clinical trials and other studies commonly assess effectiveness of an intervention through use of responder-based endpoints. These classify patients based on whether they meet a number of criteria which often involve continuous variables categorised as being above or below a threshold. The proportion of patients who are responders is estimated and, where relevant, compared between groups. An alternative method called the augmented binary method keeps the definition of the endpoint the same but utilises information contained within the continuous component to increase the power considerably (equivalent to increasing the sample size by >30%). In this article we summarise the method and investigate the variety of clinical conditions that use endpoints to which it could be applied. Methods We reviewed a database of physiological and mortality trial endpoints recommended for collection in clinical trials of different disorders. We identified responder-based endpoints where the augmented binary method would be useful for increasing power. Results We identified 68 new clinical areas where endpoints were used that would be more efficiently analysed using the augmented binary method. Conclusions The augmented binary method can potentially provide large benefits in a vast array of clinical areas. Further methodological development is needed to account for some types of endpoint.

scholarly journals Analysis of responder-based endpoints: improving power through utilising continuous components

2019 ◽  
Author(s):  
James Wason ◽  
Martina McMenamin ◽  
Susanna Dodd
Keyword(s):  
Clinical Trials ◽  
Continuous Variables ◽  
Continuous Component ◽  
Core Outcome Sets ◽  
Binary Method ◽  
Continuous Components ◽  
Clinical Disorders ◽  
Trial Endpoints ◽  
Definition Of ◽  
Clinical Conditions

Abstract Background Clinical trials and other studies commonly assess effectiveness of an intervention through use of responder-based endpoints. These classify patients based on whether they meet a number of criteria which often involve continuous variables categorised as being above or below a threshold. The proportion of patients who are responders is estimated and, where relevant, compared between groups. An alternative method called the augmented binary method keeps the definition of the endpoint the same but utilises information contained within the continuous component to increase the power considerably (equivalent to increasing the sample size by >30%). In this article we summarise the method and investigate the variety of clinical conditions that use endpoints to which it could be applied. Methods We reviewed a database of Core Outcome Sets (COS) that covered physiological and mortality trial endpoints recommended for collection in clinical trials of different disorders. We identified responder-based endpoints where the augmented binary method would be useful for increasing power. Results Out of the 287 COS reviewed, we identified 67 new clinical areas where endpoints were used that would be more efficiently analysed using the augmented binary method. Clinical areas that had particularly high numbers were rheumatology (11 clinical disorders identified), non-solid tumour oncology (10 identified), neurology (9 identified), and cardiovascular (8 identified) Conclusions The augmented binary method can potentially provide large benefits in a vast array of clinical areas. Further methodological development is needed to account for some types of endpoint.

scholarly journals Analysis of responder-based endpoints: improving power through utilising continuous components

2020 ◽  
Author(s):  
James Wason ◽  
Martina McMenamin ◽  
Susanna Dodd
Keyword(s):  
Clinical Trials ◽  
Continuous Variables ◽  
Continuous Component ◽  
Core Outcome Sets ◽  
Binary Method ◽  
Continuous Components ◽  
Clinical Disorders ◽  
Trial Endpoints ◽  
Definition Of ◽  
Clinical Conditions

Abstract Background: Clinical trials and other studies commonly assess effectiveness of an intervention through use of responder-based endpoints. These classify patients based on whether they meet a number of criteria which often involve continuous variables categorised as being above or below a threshold. The proportion of patients who are responders is estimated and, where relevant, compared between groups. An alternative method called the augmented binary method keeps the definition of the endpoint the same but utilises information contained within the continuous component to increase the power considerably (equivalent to increasing the sample size by >30%). In this article we summarise the method and investigate the variety of clinical conditions that use endpoints to which it could be applied.Methods : We reviewed a database of Core Outcome Sets (COS) that covered physiological and mortality trial endpoints recommended for collection in clinical trials of different disorders. We identified responder-based endpoints where the augmented binary method would be useful for increasing power.Results: Out of the 287 COS reviewed, we identified 67 new clinical areas where endpoints were used that would be more efficiently analysed using the augmented binary method. Clinical areas that had particularly high numbers were rheumatology (11 clinical disorders identified), non-solid tumour oncology (10 identified), neurology (9 identified), and cardiovascular (8 identified)Conclusions: The augmented binary method can potentially provide large benefits in a vast array of clinical areas. Further methodological development is needed to account for some types of endpoint.

Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 Enhances the Ability of SLE Responder Index to Identify Responders in Clinical Trials

2011 ◽  
Vol 38 (11) ◽  
pp. 2395-2399 ◽  
Author(s):  
ZAHI TOUMA ◽  
DAFNA D. GLADMAN ◽  
DOMINIQUE IBAÑEZ ◽  
SHAHRZAD TAGHAVI-ZADEH ◽  
MURRAY B. UROWITZ
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Systemic Lupus ◽  
Original Definition ◽  
Definition Of

Objective.To evaluate the performance of the Systemic Lupus Erythematosus (SLE) Responder Index (SRI) when the SLE Disease Activity Index 2000 (SLEDAI-2K) is substituted with SLEDAI-2K Responder Index-50 (SRI-50), a valid and reliable index of disease activity improvement. Also, to determine whether the SRI-50 will enhance the ability of SRI in detecting responders.Methods.Our study was conducted on patients who attended the Lupus Clinic from September 2009 to September 2010. SLEDAI-2K, SRI-50, the British Isles Lupus Assessment Group measure, and the Physician’s Global Assessment were determined initially and at followup. SRI was determined at the followup visit according to its original definition using the SLEDAI-2K score and by substituting SLEDAI-2K with SRI-50.Results.A total of 117 patients with SLEDAI-2K ≥ 4 at baseline were studied. Patients had 1 followup visit over a 3-month period. Twenty-nine percent of patients met the original definition of SRI and 35% of patients met the definition of SRI when SLEDAI-2K was substituted with SRI-50. The use of SRI-50 allowed determination of significant improvement in 7 additional patients. This improvement could not be discerned with the use of SLEDAI-2K as a component of SRI. At followup visits that showed improvement, SRI-50 scores decreased to a greater extent than SLEDAI-2K scores (p < 0.0001).Conclusion.SRI-50 enhances the ability of SRI to identify patients with clinically important improvement in disease activity. SRI-50 was superior to SLEDAI-2K in detecting partial clinical improvement, ≥ 50%, between visits. These properties of the SRI-50 enable it to be used as an independent outcome measure of improvement or as a component of SRI in clinical trials.

scholarly journals Defining the Threshold of Permissible Risk for Non-therapeutic Clinical Trials with Children in Europe

2017 ◽  
Vol 24 (4) ◽  
pp. 414-431
Author(s):  
Katherine Wade*
Keyword(s):  
Clinical Trials ◽  
Medical Care ◽  
Medicinal Products ◽  
Council Of Europe ◽  
Therapeutic Trials ◽  
Research With Children ◽  
Individual Trial ◽  
The One ◽  
Definition Of ◽  
Trial Participants

Abstract It is important that clinical research with children is encouraged so that they are not exposed to the dangers of extrapolation from adult treatments. Clinical trials with investigational medicinal products (imps) are an important part of improving medical care for children. Both the 2001 Clinical Trials Directive and the 2014 Regulation recognise the need for such research, including the need for non-therapeutic trials with imps. However, it is also recognised that a balance must be struck between permitting tailored medical care for children as a group on the one hand, and protecting individual trial participants from harm on the other. A central issue in striking this balance relates to defining the threshold of risk which should be permitted in such research. This article provides a critical analysis of the current European law in relation to the definition of acceptable risk for non-therapeutic clinical trials with imps and makes recommendations for reform, drawing on law from the Council of Europe, as well as law from the us.

The Role of the Information Contained in School Physical Evaluation Forms in Preventing the Development of Severe Clinical Conditions in Physical Education Classes

2020 ◽  
pp. 29-36
Author(s):  
Zhanna Vladimirovna Gudinova ◽  
Galina Nikolaevna Zhernakovа ◽  
Irina Vladimirovna Gegechkori ◽  
Elena Ivanovna Tolkova ◽  
Yuliya Sergeevna Vaskovskaya
Keyword(s):  
Public Schools ◽  
Physical Education ◽  
Russian Federation ◽  
Ministry Of Health ◽  
Physical Evaluation ◽  
Conflicting Information ◽  
The Russian Federation ◽  
Definition Of ◽  
Clinical Conditions ◽  
Development Assessment

This research analyses school physical evaluation forms obtained from one of Omsk public schools’ roll books as well as the physical development assessment of 820 students of this school. The findings uncovered a violation of the requirements of SanPiN, the provisions of the Russian Federation Ministry of Health orders regarding the maintenance of physical evaluation forms, the definition of medical groups for students in physical education, and conflicting information about the children’s health, which may cause severe clinical conditions in physical education classes. The noncompliance of the regulatory framework for RPN (in terms of the Health List) and the Russian Federation Ministry of Health (in terms of physical education regulation for children with accommodations) was also uncovered.

scholarly journals Practical and conceptual issues of clinical trial registration for Brazilian researchers

2015 ◽  
Vol 134 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Carolina Gomes Freitas ◽  
Thomas Fernando Coelho Pesavento ◽  
Maurício Reis Pedrosa ◽  
Rachel Riera ◽  
Maria Regina Torloni
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
International Committee ◽  
New Drugs ◽  
Trial Registration ◽  
Clinical Trial Registry ◽  
Clinical Trial Registration ◽  
Registration Process ◽  
Trial History ◽  
Definition Of

CONTEXT AND OBJECTIVE: Clinical trial registration is a prerequisite for publication in respected scientific journals. Recent Brazilian regulations also require registration of some clinical trials in the Brazilian Clinical Trials Registry (ReBEC) but there is little information available about practical issues involved in the registration process. This article discusses the importance of clinical trial registration and the practical issues involved in this process. DESIGN AND SETTING: Descriptive study conducted by researchers within a postgraduate program at a public university in São Paulo, Brazil. METHODS: Information was obtained from clinical trial registry platforms, article reference lists and websites (last search: September 2014) on the following topics: definition of a clinical trial, history, purpose and importance of registry platforms, the information that should be registered and the registration process. RESULTS: Clinical trial registration aims to avoid publication bias and is required by Brazilian journals indexed in LILACS and SciELO and by journals affiliated to the International Committee of Medical Journal Editors (ICMJE). Recent Brazilian regulations require that all clinical trials (phases I to IV) involving new drugs to be marketed in this country must be registered in ReBEC. The pros and cons of using different clinical trial registration platforms are discussed. CONCLUSIONS: Clinical trial registration is important and various mechanisms to enforce its implementation now exist. Researchers should take into account national regulations and publication requirements when choosing the platform on which they will register their trial.

scholarly journals Post-Exposure Effects of Vaccines on Infectious Diseases

2019 ◽  
Author(s):  
Tara Gallagher ◽  
Marc Lipsitch
Keyword(s):  
Clinical Trials ◽  
Observational Studies ◽  
Case Fatality ◽  
Hepatitis E ◽  
Vaccine Preventable Diseases ◽  
Post Exposure ◽  
Vaccine Trials ◽  
Tick Borne Encephalitis ◽  
Pubmed Database ◽  
Definition Of

AbstractMany available vaccines have demonstrated post-exposure effectiveness, but no published systematic reviews have synthesized these findings. We searched the PubMed database for clinical trials and observational human studies concerning the post-exposure vaccination effects, targeting infections with an FDA-licensed vaccine plus dengue, hepatitis E, malaria, and tick borne encephalitis, which have licensed vaccines outside of the U.S. Studies concerning animal models, serologic testing, and pipeline vaccines were excluded. Eligible studies were evaluated by definition of exposure, and their attempt at distinguishing pre- and post-exposure effects was rated on a scale of 1-4. We screened 4518 articles and ultimately identified 14 clinical trials and 31 observational studies for this review, amounting to 45 eligible articles spanning 7 of the 28 vaccine-preventable diseases. For secondary attack rate, this body of evidence found the following medians for post-exposure vaccination effectiveness: hepatitis A: 85% (IQR: 28; 5 sources), hepatitis B: 85% (IQR: 22; 5 sources), measles: 83% (IQR: 21; 8 sources), varicella: 67% (IQR: 48; 9 sources), smallpox: 45% (IQR: 39; 4 sources), and mumps: 38% (IQR: 7; 2 sources). For case fatality proportions resulting from rabies and smallpox, the vaccine efficacies had medians of 100% (IQR: 0; 6 sources) and 63% (IQR: 50; 8 sources) post-exposure. Although mainly used for preventive measures, many available vaccines can modify or preclude disease if administered after exposure. This post-exposure effectiveness could be important to consider during vaccine trials and while developing new vaccines.

Current Clinical Trials in Dry AMD and the Definition of Appropriate Clinical Outcome Measures

2011 ◽  
Vol 26 (3) ◽  
pp. 167-180 ◽  
Author(s):  
Zohar Yehoshua ◽  
Philip J. Rosenfeld ◽  
Thomas A. Albini
Keyword(s):  
Clinical Trials ◽  
Clinical Outcome ◽  
Outcome Measures ◽  
Dry Amd ◽  
Definition Of

scholarly journals Capillaroscopy as an Outcome Measure for Clinical Trials on the Peripheral Vasculopathy in SSc—Is It Useful?

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Maurizio Cutolo ◽  
Alberto Sulli ◽  
Carmen Pizzorni ◽  
Vanessa Smith
Keyword(s):  
Clinical Trials ◽  
Systemic Sclerosis ◽  
Outcome Measure ◽  
Digital Ulcers ◽  
Nailfold Videocapillaroscopy ◽  
Therapeutic Trials ◽  
Specific Serum ◽  
Pulmonary Arterial ◽  
Microvascular Impairment ◽  
Clinical Conditions

Peripheral microvascular impairment in systemic sclerosis (SSc) may be easily detected and scored in a safe noninvasive way by nailfold videocapillaroscopy (NVC). The paper highlights clinical conditions related to SSc in which NVC may represent an outcome measure of therapeutical interventions, by elaborating on their already assessed relationship with the NVC patterns and eventually scores. The 3 important biological/clinical conditions are: the positivity for SSc-specific serum autoantibodies, the presence of SSc skin digital ulcers (DUs) and of pulmonary arterial hypertension (PAH) SSc associated. In conclusion, to the question if capillaroscopy (NVC) may represent in SSc an outcome measure for clinical trials on the peripheral vasculopathy, based on the growing evidence and our detailed studies, the answer is positive. Recent therapeutic trials in SSc are confirming this role, and the experience is growing rapidly.

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