Institutional Review Board Oversight Research Articles

Ethical considerations for nurse practitioners conducting research in populations with opioid use disorder.

People with opioid use disorder (OUD) are a vulnerable population who face unique risks of harm when participating in research. Despite a long-standing dialogue, written research codes of ethics, and institutional review board oversight for the conduct of ethical research in vulnerable populations, protections for study populations with OUD is rarely mentioned. Nurse practitioners who conduct research using participants with OUD, especially when recruiting their own patients (i.e., dual role), must be aware of the unique ethical considerations necessary to protect their patients and participants from increased risks. This article explores vulnerabilities and influences that can affect participant recruitment and consent, imbalances in the distribution of risk and benefits to participants participating in research, and the concerns of coercions, undue influence, and unjustifiable pressure contributing to vulnerabilities. Strategies to reduce the risks of influences that are of concern in the vulnerable population of research participants with opioid disorder are suggested. The goal of this article was to raise awareness of the unique potential risks of harm when using people with OUD as research participants and to explore strategies to minimize potential risks of various levels of influence in this vulnerable population.

The Quality Improvement Review Board: An Innovative Approach to Oversight of Projects That Do Not Meet Criteria of Human Subject Research.

This article describes the development of an institutional quality improvement review board (QIRB) as an effective and efficient method for reviewing and overseeing institutional quality improvement (QI) initiatives. QI projects involve the systematic collection and analysis of data and the implementation of interventions designed to improve the quality of clinical care and/or educational programs for a distinct population in a specific setting. QI projects are fundamentally distinct from human subjects research (HuSR); however, the differences between them are subtle and highly nuanced. Determining whether a project meets the definition of QI or qualifies as HuSR, thus requiring institutional review board (IRB) review, can be confusing and frustrating. Nevertheless, this distinction is highly consequential due to the heavy regulatory requirements involved in HuSR and IRB oversight. Making the correct determination of a project's regulatory status is essential before the project begins. Project leaders may not realize that their work meets the definition of HuSR and, therefore, might conduct the project without appropriate IRB review. Therefore, best practices dictate that project leaders should not decide which type of institutional review is appropriate for their projects. In addition, when QI project teams attempt to disseminate the results of their work, documentation of formal review and approval is generally required by peer-reviewed journals and professional organizations. However, institutional review mechanisms are rarely available. Projects that do not meet the definition of HuSR fall outside the purview of IRBs and most institutions do not have an alternative review body. This creates frustration for both project leaders and IRB administrators. Apart from IRB review, a separate process for reviewing QI projects offers several benefits. These include (1) relieving the burden on busy IRB staff; (2) promoting scholarly activity; (3) protecting the institution, project leaders, and participants from HuSR conducted outside of appropriate IRB review; and (4) promoting rigorous QI methods.

Seasonal Association With Hypothermia inCombat Trauma.

Hypothermia increases mortality in trauma populations and frequently occurs in military casualties due to the nature of combat environments. The association between hypothermia and the time of year when injured remains unclear. We sought to determine the association between seasonal changes in temperature and hypothermia among combat casualties. This observational study was a secondary analysis of a previously described Department of Defense Trauma Registry dataset which included U.S. military and Coalition casualties who received prehospital care from January 2007 to March 2020 in Afghanistan and Iraq. We tested for associations between hypothermia (<36.2°C) and seasonal ambient temperatures by constructing multivariable logistic regression models. Summer was defined as June through August and winter as December through February. We assumed that the combat operations occurred in the area near the point of first contact with the deployed military treatment facilities. This study was determined to be exempt from Institutional Review Board oversight. There were 5,821 that met inclusion for this study. Within the multivariable logistic regression model, we adjusted for injury severity score, mechanism of injury, and imputed transport time, finding that combat casualties were 2.28 (odds ratio, 95% confidence interval 1.93-2.69) times more likely to develop hypothermia in the winter versus summer. When using temperature as a continuous outcome, casualties had a lower emergency department temperature during the winter (parameter estimate -0.133°C, P < 0.001) after adjusting for confounders. In casualties experiencing hypothermia, mortality was higher (4% versus 1%, P < 0.001), and composite median injury severity score values were higher (10 versus 5, P < 0.001). Among hypothermic casualties, serious injuries were significantly more common (all P < 0.001) to the head (15% versus 7%), thorax (15% versus 7%), abdomen (9% versus 6%), extremities (35% versus 22%), and skin (4% versus 2%). We found a seasonal variation in the occurrence of hypothermia in a large cohort of trauma casualties. Despite adjustment for multiple known confounders, our findings substantiate probable ambient temperature variations to trauma-induced hypothermia. Furthermore, our findings, when taken in the context of other studies on the efficacy of current hypothermia prevention and treatment strategies, support the need for better methods to mitigate hypothermia in future cold-weather operations.

Continuous Improvement, Institutional Review Boards, and Resistance to Practitioner Scholarship

In this essay, we explore the tension between research using continuous improvement (CI) paradigms, such as improvement science, and conventional research, and the role and regulation of Institutional Review Board (IRB) oversight. We argue that the current regulatory structure privileges traditional research and hinders collaborative inquiry that centers the voice and agency of those traditionally marginalized. We also question whether IRBs should limit CI efforts required of educational leaders as part of their jobs. We offer recommendations for how IRBs and scholar-practitioners can together support CI efforts.

Child health valuation protocol for a discrete choice experiment comparing paired comparison and kaizen tasks and estimating US EQ-5D-Y-3L values on an experience scale

IntroductionA decade ago, the first national valuation study of the EQ-5D-Y-3L (Y-3L) involved a discrete choice experiment (DCE) that asked 4155 US adult respondents to complete 40 paired comparisons, choosing...

Assessing Resident Well-Being: Ethical Considerations for Researchers When Conducting Qualitative Wellness Research With Resident Populations.

Assessing Resident Well-Being: Ethical Considerations for Researchers When Conducting Qualitative Wellness Research With Resident Populations.

The Harraseeket Conference – Revisiting systems for ethics oversight of research with human participants

The current system of ethical oversight in the United States is based on Institutional Review Board (IRB) review. The system was established in response to well-known and egregious mistreatment of subjects in both biomedical and social and behavioral research. In the decades since the research regulations were enacted, reaction to the burden of IRB oversight has led the system to focus on compliance and limit its active oversight disproportionately to studies that could present the risk of physical harm. At the same time, the characteristics of the research enterprise have changed and methodologies now present novel risks that were not envisioned in the regulations. We convened a group of IRB professionals, academic leaders, and others to discuss limitations of the current system, how that system could be changed to recognize evolving risks and an increasing focus on participant and community voice, and how it could better serve the needs of researchers and support the societal project of science as a public good. Recommendations included a call to reexamine the academic incentive structure, to develop a system to support consideration of ethical principles from the time of study design, and to explicitly provide different ethical support and oversight for high-risk interventional trials and lower risk biomedical and social behavioral research.

Aspects of the CPRRD Affecting Xenotransplantation Research in Human Heart-beating Brain-dead Decedents.

Aspects of the CPRRD Affecting Xenotransplantation Research in Human Heart-beating Brain-dead Decedents.

Trial of ultrasound guided carpal tunnel release versus traditional open release (TUTOR).

Background:Carpal tunnel release (CTR) is a surgical treatment option for patients with carpal tunnel syndrome (CTS) symptoms that are unresponsive to conservative treatment. Most patients experience symptomatic relief after CTR regardless of the surgical technique. However, direct comparisons of the safety and effectiveness between CTR surgical techniques are limited. The purpose of this randomized controlled trial is to compare the safety and effectiveness of CTR with ultrasound guidance (CTR-US) versus mini-open CTR (mOCTR) in subjects with symptomatic CTS.Design and methods:TUTOR (Trial of Ultrasound guided CTR versus Traditional Open Release) is a randomized controlled trial in which 120 subjects at up to 12 sites in the United States will be randomized (2:1) to receive CTR-US or mOCTR. The primary endpoint of the study is the percentage of patients who return to normal daily activities within 3 days of the procedure. Secondary endpoints of the study are median time to return to normal daily activities, percentage of patients who return to work within 3 days of the procedure, median time to return to work, Boston Carpal Tunnel Questionnaire Symptom Severity Scale (BCTQ-SSS) change score at 3 months, BCTQ Functional Status Scale (BCTQ-FSS) change score at 3 months, Numeric Pain Scale change score at 3 months, EuroQoL-5 Dimension 5-Level (EQ-5D-5L) change score at 3 months, and the incidence of device- or procedure-related adverse events at 3 months. Patient follow-up in this trial will continue for 1 year.Ethics and dissemination:This study was approved by a central institutional review board and ongoing trial oversight will be provided by a data safety monitoring board (DSMB). The authors intend to report the results of this trial at medical conferences and peer-reviewed journals. The outcomes of TUTOR will have important clinical and economic implications for all stakeholders involved in treating patients with CTS.Study registration:ClinicalTrials.gov (https://clinicaltrials.gov): NCT05405218.Level of evidence:1

Dental hygiene educators' knowledge and implementation of objective structured clinical examination in United States dental hygiene programs.

In 2021, the American Dental Association (ADA) announced the intention to develop a standardized dental hygiene licensure objective structured clinical examination (DHLOSCE). The purpose of this study was to measure the United States (US) dental hygiene (DH) educators' foundational knowledge of OSCE development and delivery in light of the impending development of the DHLOSCE by the ADA's Testing Services. The study was determined to be exempt from Institutional Review Board oversight. A 21-question survey was developed, pilot tested, and electronically disseminated through Qualtrics. The survey recruitment was emailed to the directors of all entry-level DH education programs in the US (n = 328), asking them to participate in the survey and to forward it to the clinical faculty in their institutions. Descriptive and inferential statistics were utilized to analyze the data. There were 143 study participants, for a completion rate of 45%. Over two-thirds of respondents (64%) were unaware of the plans to develop the DHLOSCE, while 13% reported utilizing OSCEs to meet accreditation standards. Only 3% reported receiving a formal education in OSCE development compared to 29% who learned through a colleague or peer. Nearly half reported a lack of faculty experience as a barrier to OSCE implementation. Over three-quarters, 76% reported a lack of OCSE development committees within their program and only 14% had experience developing an OSCE station. The study results suggest an urgent need for the development of OSCE training resources specific to DH education, as programs across the US prepare for the impending DHLOSCE.

Chronic Pain–Related Jaw Muscle Motor Load and Sensory Processing

Chronic pain associated with temporomandibular disorders (TMDs) may reflect muscle mechanoreceptor afferent barrage and dysregulated sensory processing. This observational study tested for associations between Characteristic Pain Intensity (CPI), physical symptoms (Patient Health Questionnaire–15 [PHQ-15]), and cumulative jaw muscle motor load (mV*s). In accordance with institutional review board oversight and Strengthening the Reporting of Observational Studies in Epidemiology guidelines, adult subjects gave informed consent and were identified via Diagnostic Criteria for TMD (DC-TMD) examination and research protocols. Subjects were assigned to ±Pain groups using DC-TMD criteria for myalgia. CPI scores characterized pain intensity. PHQ-15 scores were surrogate measures of dysregulated sensory processing. Laboratory tests were performed to quantify masseter and temporalis muscle activities (mV) per bite force (N) for each subject. In their natural environments, subjects recorded day- and nighttime electromyography from which cumulative jaw muscle motor loads (mV*s) were determined for activities consistent with bite forces of >1 to ≤2 and >2 to ≤5 N. Data were assessed using univariate analysis of variance, simple effects tests, K-means cluster classification, and 3-dimensional regression analyses. Of 242 individuals screened, 144 enrolled, and 125 with complete data from study protocols, there were 35 females and 15 males for +Pain and 35 females and 40 males for −Pain. Subjects produced 324 daytime and 341 nighttime recordings of average duration 6.9 ± 1.7 and 7.6 ± 1.7 h, respectively. Overall, +Pain compared to −Pain subjects had significantly higher (all P ≤ 0.002) CPI and PHQ-15 scores. Cumulative jaw muscle motor loads showed significant between-subject effects for time, diagnostic group, and sex (all P < 0.003), where motor loads tended to be higher for daytime versus nighttime, +Pain versus −Pain groups, and males versus females. Two clusters were identified, and regression relations showed associations of low-magnitude daytime masseter motor load, PHQ-15, and CPI scores for cluster 1 (n = 105, R2 = 0.44) and cluster 2 (n = 18, R2 = 0.80). Furthermore, these regression relations showed thresholds of motor load and PHQ-15 scores, above which there were nonlinear increases in reported pain.

Strategies to Manage Drugs and Devices Approved Based on Limited Evidence: Results of a Modified Delphi Panel.

Prescription drugs and medical devices are increasingly coming to market through expedited US Food and Drug Administration (FDA) pathways that require only limited evidence of safety and efficacy, such as nonrandomized, unblinded trial data in small numbers of patients, or the use of surrogate end points. Reliance on more limited evidence means that there is often greater uncertainty about risks and benefits. Using a modified Delphi process, we sought to identify promising policy approaches that address physician-patient decision-making needs about the use of such drugs and medical devices. We convened 13 national leaders from academia, government, nonprofits, payors, and industry who had expertise in medical product regulation, payor policymaking, bioethics, physician practice, patient advocacy, public health expertise/advocacy, clinical trials, the pharmaceutical and device industry, institutional review board oversight, and real-world evidence. Through multiple rounds of voting and meetings focused on evaluating the feasibility and impact of various interventions, the 13 participants reached the broadest consensus on 4 interventions: strengthening FDA post-approval study requirements to ensure postmarket evidence is generated in a timely manner, better informing patients about the risks and benefits and level of evidence supporting therapies via simplified and patient-centered product information "boxes" modeled on nutrition labels, limiting prices for drugs and medical devices approved based on surrogate end point data until confirmatory clinical evidence is generated, and improving health professional education about FDA regulation to better support clinician use of drugs and devices as well as communication with patients.

Implications of the Revised Common Rule for Qualitative Health Research: Opportunities, Concerns, and Recommendations.

In January 2019, revisions to federal regulations that outline requirements for ethical oversight of human subjects research (The Revised Common Rule) went into effect. These revisions reflect major changes in thinking about risk and protection of research subjects. The Revised Common Rule (RCR) considerably curtails federal oversight of social and behavioral science, with most non-interventional research and "benign" behavioral interventions becoming exempt from mandated Institutional Review Board (IRB) approval, although determination of exemption remains with IRBs. As two qualitative health researchers serving on IRBs, we consider how this contraction of federal oversight dovetails with longstanding criticisms of IRB oversight of qualitative research. We explore the passage of the RCR as a point of potentially important change in procedure and principle in relation to ethical oversight of qualitative health research. We identify challenges and opportunities with these changes at the institutional, professional, and individual levels for ethical and impactful qualitative research.

Impact of Coronavirus Disease 2019 on the Diagnosis and Therapy for Barrett’s Esophagus and Esophageal Cancer in the United States

Impact of Coronavirus Disease 2019 on the Diagnosis and Therapy for Barrett’s Esophagus and Esophageal Cancer in the United States

Committee on High-quality Alzheimer's Disease Studies (CHADS) consensus report.

BackgroundConsensus guidance for the development and identification of high‐quality Alzheimer's disease clinical trials is needed for protocol development and conduct of clinical trials.MethodsAn ad hoc consensus committee was convened in conjunction with the Alzheimer's Association to develop consensus recommendations.ResultsConsensus was readily reached for the need to provide scientific justification, registration of trials, institutional review board oversight, conflict of interest disclosure, funding source disclosure, defined trial population, recruitment resources, definition of the intervention, specification of trial duration, appropriate payment for participant engagement, risk‐benefit disclosure as part of the consent process, and the requirement to disseminate and/or publish trial results even if the study is negative.ConclusionsThis consensus guidance should prove useful for the protocol development and conduct of clinical trials, and may further provide a platform for the development of education materials that may help guide appropriate clinical trial participation decisions for potential trial participants and the general public.

Impact of Pharmacist Involvement on the Utility of a Gram-Negative Blood Culture Identification Panel on Antimicrobial Usage.

Background: A rapid molecular diagnostic test (MDT) is a test used to identify several different species of gram-negative bacteria and their genetic resistance markers. However, the impact of rapid MDT has not been established when combined with pharmacist involvement. Objective: To determine the impact of pharmacy involvement on patient outcomes when using rapid MDT. The primary outcome is the time from gram stain result to the first dose of the targeted antibiotic. Methods: This is a single-center, quasi-experimental, 1-group pretest-posttest design study of patients with gram-negative bacteremia in a community hospital. Hospitalized patients 18 years or older were included if they had a gram-negative blood culture. Patients were excluded if they were discharged or expired prior to culture results. Outcomes were compared between patients prior to and after implementation of the automated MDT. This research was determined to be exempt from institutional review board oversight consistent with West Florida Healthcare and in accordance with institutional policy. Results: The use of rapid MDT combined with pharmacist intervention resulted in a statistically significant decrease in the time to targeted antibiotic therapy (pre-intervention group, n = 77, 44.8 ± 17.8 hours versus post-intervention group, n= 80, 4.4 ± 5.8 hours; P ≤.001). There was no significant difference found between secondary outcomes. Limitations included small sample size as well as inconsistent documentation. Conclusions: The use of rapid MDT combined with pharmacist intervention resulted in a statistically significant decrease in the time to targeted antibiotic therapy.

Admission Characteristics and Mortality Risk Among Patients Hospitalized with COVID-19.

Admission Characteristics and Mortality Risk Among Patients Hospitalized with COVID-19.

Using business intelligence and data visualization to understand the characteristics of failed appointments in dental school clinics.

Broken appointments are an important cause of waste in health care. Patients who fail to attend incur costs to providers, deny trainees learning opportunities, and impact their own health as well as that of other patients who are waiting for care. A total of 410,000 appointment records over 3 years were extracted from our electronic health record. We conducted exploratory data analysis and assessed correlations between appointment no-shows and other attributes of the appointment and the patient. The University of Michigan Medical School's Committee on Human Research reviewed the study and deemed that no Institutional Review Board oversight was necessary for this quality improvement project that was, retrospectively, turned into a study with previously de-identified data. The patient's previous attendance record is the single most significant correlation with attendance. We found that patients who said they are "scared" of dental visits were 62% as likely to attend as someone reporting "no problem." Patients over 65 years of age have better attendance rates. There was a positive association between receiving email/text confirmation and attendance. A total of 94.9% of those emailed a reminder and 92.2% of those who were texted attended their appointment. We were able to identify relationships of several variables to failed and attended appointments that we were previously unknown to us. This knowledge enabled us to implement interventions to support better attendance at Dental Clinics at the University of Michigan, improving patient health, student training, and efficient use of resources.

The History of Human Subjects Research and Rationale for Institutional Review Board Oversight.

The history of human subjects research and the abuses that led to the creation of the United States' (US) regulatory schema for research, which includes institutional review boards (IRBs), is long and complex. However, when one understands the history, one can see direct links between those abuses and the regulations, as well as the ethical principles, contained in the Belmont Report. To that end, we provide a brief analysis of the history of human subjects research and its abuses, including a lesser known case (the atrocities committed by Nazi scientists and physicians during World War II) and infamous cases in the US (including the Tuskegee Syphilis Study and Willowbrook). With that history in hand, we will then seek to understand the regulations that govern human subjects research and the IRB by grounding them both in the ethical principles in the Belmont Report.

Development and External Validation of a Clinical Decision Support Tool for Managing Children with Minor Head Trauma and Intracranial Injuries

Background: There are no validated tools guiding the appropriate level-of-care for children with minor head trauma (MHT) and radiographic intracranial injuries. We developed and externally validated a clinical decision support tool for risk-stratifying these patients. Methods: The derivation cohort included children enrolled in the PECARN head injury study from 2004-2006. The validation group consisted of a separate cohort of children with MHT treated at six centers from 2006-2019. Children < 18 years were included if they presented within 24 hours of injury, had a Glasgow Coma Scales (GCS) score of 13-15, and had intracranial injury on neuroimaging. A risk model was developed using recursive partitioning to predict serious neurological events, defined as neurosurgical intervention, intubation longer than 24 hours due to head injury, or death from head injury. Risk thresholds were determined for clinical decision-making. This model was compared to a logistic regression model previously developed using the PECARN cohort. Findings: Based on 839 patients meeting inclusion criteria in the PECARN cohort, the tree-based model included seven predictors, with midline shift, depressed skull fracture, epidural hematoma, and GCS score being the most influential. Three risk thresholds were evaluated to classify patients as ‘low’ risk. In the validation cohort consisting of 1,630 patients, the most conservative cutoff (i.e. any predictor present) identified 119/119 children with serious neurological events (sensitivity 100%; 95% CI 96·9-100), but had the lowest specificity (26.3%; 95% CI 24·1-28·6). All three thresholds had negative predictive values above 99% and collectively outperformed the logistic regression model. Using these thresholds, a clinical decision support tool was created that identified 75% of the population as ‘low’ or ‘very low’ risk. Interpretation: We developed and validated a clinical decision support tool that accurately risk-stratifies children with MHT and radiographic intracranial injuries. This tool can potentially improve patient safety and reduce resource use. Funding : Thrasher Research Fund and the Agency for Healthcare Research and Quality. Funding Statement: This study was funded by grants from the Agency for Healthcare Research and Quality (1F32HS027075-01A1) and the Thrasher Research Fund (#15024). Declaration of Interests: MAO reports grant funding from Merck, Sanofi Pasteur, and Pfizer, and consulting fees from Pfizer. EJ reports medical expert testimony and patent holdings (US Patent 9993631). DDL has received research funds and/or research equipment for unrelated projects from Medtronic, Inc., Karl Storz, Inc., and Microbot Medical, Inc, and has received philanthropic equipment contributions for humanitarian relief work from Karl Storz, Inc. and Aesculap, Inc. No other authors disclose any competing interests. Ethics Approval Statement: All data analyzed were from the deidentified, public-use dataset, and consequently the Washington University in St. Louis Human Research Protection Office deemed the analysis not subject to institutional review board (IRB) oversight.