A simulation study using the hybrid statistic and the meta-analysis t-test for data with matched and unmatched subjects in the interim analysis of clinical trials

An interim analysis is usually applied in later phase II or phase III trials to find convincing evidence of a significant treatment difference that may lead to trial termination at an earlier point than planned at the beginning. This can result in the saving of patient resources and shortening of drug development and approval time. In addition, ethics and economics are also the reasons to stop a trial earlier. In clinical trials of eyes, ears, knees, arms, kidneys, lungs, and other clustered treatments, data may include distribution-free random variables with matched and unmatched subjects in one study. It is important to properly include both subjects in the interim and the final analyses so that the maximum efficiency of statistical and clinical inferences can be obtained at different stages of the trials. So far, no publication has applied a statistical method for distribution-free data with matched and unmatched subjects in the interim analysis of clinical trials. In this simulation study, the hybrid statistic was used to estimate the empirical powers and the empirical type I errors among the simulated datasets with different sample sizes, different effect sizes, different correlation coefficients for matched pairs, and different data distributions, respectively, in the interim and final analysis with 4 different group sequential methods. Empirical powers and empirical type I errors were also compared to those estimated by using the meta-analysis t-test among the same simulated datasets. Results from this simulation study show that, compared to the meta-analysis t-test commonly used for data with normally distributed observations, the hybrid statistic has a greater power for data observed from normally, log-normally, and multinomially distributed random variables with matched and unmatched subjects and with outliers. Powers rose with the increase in sample size, effect size, and correlation coefficient for the matched pairs. In addition, lower type I errors were observed estimated by using the hybrid statistic, which indicates that this test is also conservative for data with outliers in the interim analysis of clinical trials.^

Attitudes and other barriers to the utilization of clinical research findings by American physicians: A systematic review

Background: The Institute of Medicine estimates that only a maximum of 25% of clinical research findings are incorporated into practice by physicians. To improve clinical practice, efforts have been made to promote evidence-based medicine and the use of clinical guidelines. Despite these efforts, the gap between research and clinical practice remains wide.^ Objective: To systematically review the literature describing the factors which influence the use of clinical research recommendations by American physicians.^ Hypothesis: Barriers exist in the application of clinical research into clinical practice, and are multifactorial. The establishment of the Clinical and Translational Awards (CTSA; special federal grants awarded to selected institutions to support clinical and translational research) has reduced the effect of these barriers and improved the process of clinical research translation into practice among American physicians.^ Aims: Identify barriers and facilitators of the use of research findings in clinical practice by American physicians. Contrast studies published six years before and after the creation of the CTSA.^ Methods: The sources of data include published literature from Medline, PubMed and PsycINFO. Selected studies must be qualitative, a survey of American clinicians, based on evidence-based medicine practice, clinical guidelines or treatment pathways. Systematic reviews and reports were excluded, as well as studies with less than 100 respondents.^ Results: In total, 1036 abstracts were reviewed; 115 full text potential articles were identified and reviewed, and a total of 31 studies met all criteria for inclusion in the final review.^ Conclusions: The barriers against the application of clinical research findings, in the forms of clinical guidelines, evidence-based medicine guides and clinical pathways, can be divided broadly into physician barriers, practice/system barriers and patient barriers. Physician barriers are the most common barriers, especially the lack of familiarity with guidelines and the lack of time. Of the factors which improve the use of research based guidelines, physician factors such as younger age, lower duration of clinical practice, specialty training, and practice in large group Health Maintenance Organization (HMO) settings with fewer patients seen were the most commonly cited.^

Clinical trials, informed consent, & emergency medicine: A systematic literature review

Background: In the United States, the Food and Drug Administration (FDA) regulates clinical trials. These regulations address good clinical practices as well as human subject protection (FDA, 2012). One of the most important legal and ethical concerns in clinical trials is informed consent. 21 CFR 50 governs human subjects research. Part 50.24 provides an emergency research exception to the informed consent requirement. Research was conducted to determine the appropriateness of this exception, whether the benefit justifies the exception, and its public health significance.^ Methods: A systematic literature review was conducted and articles were identified from peer-reviewed journals.^ Results: There is some variance in opinions regarding the appropriateness of the exception, but the literature reviewed found the study results of these trials justified the waiver.^ Conclusion: The exception to the informed consent requirement is likely appropriate and justified in emergency research when implemented within the specified guidelines.^

Ethics and health systems research in 'post'-conflict situations

Although considerable attention has been given to ethical issues related to clinical research in developing countries, in particular related to HIV therapy, there has been limited focus on health systems research, despite its increasing importance in the light of current trends in development assistance. This paper examines ethical issues related to health systems research in 'post'-conflict situations, addressing both generic issues for developing countries and those issues specific to 'post'-conflict societies, citing examples from the author's Cambodian experience. It argues that the destruction of health infrastructure results in a loss of structures and processes that would otherwise protect prospective research subjects who are part of vulnerable populations. It identifies the growth of health systems research as part of a trend towards sectoral and programmatic development assistance, the emergence of 'knowledge generation' as a form of research linked to development, and the potential for conflict where multilateral and bilateral donors are both primary funders and users of health systems research. It also examines the position of the health system researcher in relation to the sponsors of this research, and the health system being analysed.

Ethics in the provision of removable partial dentures

Aim: To investigate the construction of cobalt-chromium removable partial dentures by commercial private dental laboratories. Methods: Ninety master casts for fabrication of cobalt-chromium removable partial dentures were obtained from three commercial laboratories randomly selected. Casts were assessed for dental arch treated, Kennedy classification, cast surveying, denture design information provided by the dentist, and mouth preparation (rest seat, guiding plane and retentive area). Dental technicians answered a questionnaire regarding qualification of assisted dentists, monthly number of framework castings, and use of dental surveyor. Mouth preparation was compared among laboratories using Kruskal-Wallis test (α=0.05). Results: The percentage of Kennedy class I was 16%, class II 19%, class III 56%, and class IV 9%. The majority of master cats (51%) examined was sent to dental laboratories without any design information and did not comply with ethical guidelines in the provision of RPD. Approximately half of the casts were considered “inappropriate” for guiding planes and retentive areas. One of the laboratories presented all casts “inappropriate” for rest seat distribution (p<0.001). Conclusions: Mouth preparation frequently failed for guiding planes, retentive areas and distribution of rest seats. It is necessary to provide students with adequate clinical experience at the dental school environment, which will actually be carried into the practice of dentistry.

Ethics in the provision of removable partial dentures

Aim: To investigate the construction of cobalt-chromium removable partial dentures by commercial private dental laboratories. Methods: Ninety master casts for fabrication of cobalt-chromium removable partial dentures were obtained from three commercial laboratories randomly selected. Casts were assessed for dental arch treated, Kennedy classification, cast surveying, denture design information provided by the dentist, and mouth preparation (rest seat, guiding plane and retentive area). Dental technicians answered a questionnaire regarding qualification of assisted dentists, monthly number of framework castings, and use of dental surveyor. Mouth preparation was compared among laboratories using Kruskal-Wallis test (α=0.05). Results: The percentage of Kennedy class I was 16%, class II 19%, class III 56%, and class IV 9%. The majority of master cats (51%) examined was sent to dental laboratories without any design information and did not comply with ethical guidelines in the provision of RPD. Approximately half of the casts were considered “inappropriate” for guiding planes and retentive areas. One of the laboratories presented all casts “inappropriate” for rest seat distribution (p<0.001). Conclusions: Mouth preparation frequently failed for guiding planes, retentive areas and distribution of rest seats. It is necessary to provide students with adequate clinical experience at the dental school environment, which will actually be carried into the practice of dentistry.

Longitudinal Clinical Evaluation of Undercut Areas and Rest Seats of Abutment Teeth in Removable Partial Denture Treatment

PURPOSE: Adequate preparation of abutment teeth for removable partial denture (RPD) rest seats allows appropriate masticatory force transmission, retention, and stability of supporting structures. It follows that careful preparation will be important for the longevity of the rehabilitation. The present study aimed to clinically evaluate rest seats and undercut areas of abutment teeth in RPD wearers after 2 years of use. MATERIALS AND METHODS: A total of 193 occlusal, incisal, and cingulum rest seats were evaluated in terms of shape, rest adaptation, wear, caries, fractures, and surface type (enamel, composite resin, or amalgam). Two hundred and fourteen undercut areas were evaluated in terms of surface type (enamel or restoration) and integrity. This study was approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte, resolution 196/1996, protocol number 11/05. RESULTS: Intact preparations accounted for 92.2% of the total. Application of the Pearson test (p= 0.289) found no statistically significant differences among the materials on which the rest seats were prepared. For the undercut areas, 20.7% of those obtained on restorative material were nonintact. In addition, Fisher's exact test showed a statistically significant difference (p= 0.001) in surface type; enamel surfaces were shown to be 14 times more stable than restored surfaces. CONCLUSIONS: The results of this study suggest that rest seats are stable, regardless of the material on which they are prepared. Retentive areas were shown to be more stable when they were located in enamel.

Longitudinal Clinical Evaluation of Undercut Areas and Rest Seats of Abutment Teeth in Removable Partial Denture Treatment

PURPOSE: Adequate preparation of abutment teeth for removable partial denture (RPD) rest seats allows appropriate masticatory force transmission, retention, and stability of supporting structures. It follows that careful preparation will be important for the longevity of the rehabilitation. The present study aimed to clinically evaluate rest seats and undercut areas of abutment teeth in RPD wearers after 2 years of use. MATERIALS AND METHODS: A total of 193 occlusal, incisal, and cingulum rest seats were evaluated in terms of shape, rest adaptation, wear, caries, fractures, and surface type (enamel, composite resin, or amalgam). Two hundred and fourteen undercut areas were evaluated in terms of surface type (enamel or restoration) and integrity. This study was approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte, resolution 196/1996, protocol number 11/05. RESULTS: Intact preparations accounted for 92.2% of the total. Application of the Pearson test (p= 0.289) found no statistically significant differences among the materials on which the rest seats were prepared. For the undercut areas, 20.7% of those obtained on restorative material were nonintact. In addition, Fisher's exact test showed a statistically significant difference (p= 0.001) in surface type; enamel surfaces were shown to be 14 times more stable than restored surfaces. CONCLUSIONS: The results of this study suggest that rest seats are stable, regardless of the material on which they are prepared. Retentive areas were shown to be more stable when they were located in enamel.

Self-assessment of clinical nurse mentors as dimensions of professional development and the capability of developing ethical values among nursing students : A correlational research study

Date of Acceptance: 08/04/2015 The paper presents, in part, the results of a broader non-profit development project entitled “Advance level of knowledge for quality in clinical mentorship — professional ethics and continuously professional development”. The project was financed by the Ministry of Higher Education, Science and Sport of the Republic of Slovenia (contract no. 3211-11-000263, the number of project OP RCV_VS-11-14). The members of the development group of the project were: Brigita Skela-Savič (leader), Karmen Romih, Sanela Pivač, Katja Skinder Savić and Andreja Prebil. The research report for the entire project is available on the online bibliographic database COBIB.si, at the Faculty of Health Care Jesenice and at the Ministry of Higher Education, Science and Sport of the Republic of Slovenia.

Self-assessment of clinical nurse mentors as dimensions of professional development and the capability of developing ethical values among nursing students : A correlational research study

Date of Acceptance: 08/04/2015 The paper presents, in part, the results of a broader non-profit development project entitled “Advance level of knowledge for quality in clinical mentorship — professional ethics and continuously professional development”. The project was financed by the Ministry of Higher Education, Science and Sport of the Republic of Slovenia (contract no. 3211-11-000263, the number of project OP RCV_VS-11-14). The members of the development group of the project were: Brigita Skela-Savič (leader), Karmen Romih, Sanela Pivač, Katja Skinder Savić and Andreja Prebil. The research report for the entire project is available on the online bibliographic database COBIB.si, at the Faculty of Health Care Jesenice and at the Ministry of Higher Education, Science and Sport of the Republic of Slovenia.

Self-assessment of clinical nurse mentors as dimensions of professional development and the capability of developing ethical values among nursing students : A correlational research study

Date of Acceptance: 08/04/2015 The paper presents, in part, the results of a broader non-profit development project entitled “Advance level of knowledge for quality in clinical mentorship — professional ethics and continuously professional development”. The project was financed by the Ministry of Higher Education, Science and Sport of the Republic of Slovenia (contract no. 3211-11-000263, the number of project OP RCV_VS-11-14). The members of the development group of the project were: Brigita Skela-Savič (leader), Karmen Romih, Sanela Pivač, Katja Skinder Savić and Andreja Prebil. The research report for the entire project is available on the online bibliographic database COBIB.si, at the Faculty of Health Care Jesenice and at the Ministry of Higher Education, Science and Sport of the Republic of Slovenia.

The U.N. convention on the rights of the child: Relevance and application to pediatric clinical bioethics

This article provides an overview of the relevance and import of the U.N. Convention on the Rights of the Child (CRC) to child health practice and pediatric bioethics. We discuss the four general principles of the CRC that apply to the implementation of all rights contained in the document, the right to health articulated in Article 24, and the important position ascribed to parents in fulfilling the rights of their children. We then examine how the CRC is implemented and monitored in law and practice. The CRC and associated principles of child rights provide strategies for rights-based approaches to clinical practice and health systems, as well as to policy design, professional training, and health services research. In light of the relevance of the CRC and principles of child rights to children’s health and child health practice, it follows that there is an intersection between child rights and pediatric bioethics. Pediatric bioethicists and child rights advocates should work together to define this intersection in all domains of pediatric practice.

Systematic evaluation of patient-reported outcome (PRO) protocol content and reporting in UK cancer clinical trials: the EPiC study protocol

Introduction Emerging evidence suggests that patient-reported outcome (PRO)-specific information may be omitted in trial protocols and that PRO results are poorly reported, limiting the use of PRO data to inform cancer care. This study aims to evaluate the standards of PRO-specific content in UK cancer trial protocols and their arising publications and to highlight examples of best-practice PRO protocol content and reporting where they occur. The objective of this study is to determine if these early findings are generalisable to UK cancer trials, and if so, how best we can bring about future improvements in clinical trials methodology to enhance the way PROs are assessed, managed and reported. Hypothesis: Trials in which the primary end point is based on a PRO will have more complete PRO protocol and publication components than trials in which PROs are secondary end points.

Methods and analysis Completed National Institute for Health Research (NIHR) Portfolio Cancer clinical trials (all cancer specialities/age-groups) will be included if they contain a primary/secondary PRO end point. The NIHR portfolio includes cancer trials, supported by a range of funders, adjudged as high-quality clinical research studies. The sample will be drawn from studies completed between 31 December 2000 and 1 March 2014 (n=1141) to allow sufficient time for completion of the final trial report and publication. Two reviewers will then review the protocols and arising publications of included trials to: (1) determine the completeness of their PRO-specific protocol content; (2) determine the proportion and completeness of PRO reporting in UK Cancer trials and (3) model factors associated with PRO protocol and reporting completeness and with PRO reporting proportion.

Ethics and dissemination The study was approved by the ethics committee at University of Birmingham (ERN_15-0311). Trial findings will be disseminated via presentations at local, national and international conferences, peer-reviewed journals and social media including the CPROR twitter account and UOB departmental website (http://www.birmingham.ac.uk/cpro0r).

Exploring Forensic Nursing Ethics and Practice: Roles, Loyalties and Photodocumentation Practices

Thesis (Ph.D.)--University of Washington, 2016-08

Informed consent in clinical research: do patients understand what they have signed?

Informed consent is an essential element of research, and signing this document is required to conduct most clinical trials. Its aim is to inform patients what their participation in the study will involve. However, increasingly, their complexity and length are making them difficult to understand, which might lead patients to give their authorization without having read them previously or without having understood what is stated. In this sense, the Ethics Committees for Clinical Research, and Pharmacists specialized in Hospital Pharmacy and Primary Care in their capacity as members of said committees, play an important and difficult role in defending the rights of patients. These Committees will review thoroughly these documents to guarantee that all legal requirements have been met and, at the same time, that they are easy to understand by the potential participants in a clinical trial.