Faculty Bibliography

Policies have been developed to protect vulnerable populations in clinical research, including the US federal research regulations (45 Code of Federal Regulations 46 Subparts B, C, and D). These policies generally recognize vulnerable populations to include pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. The aim has been to protect these populations from harm, often by creating regulatory and ethical checks that may limit their participation in many clinical trials. The recent increase in pragmatic clinical trials raises at least two questions about this approach. First, is exclusion itself a harm to vulnerable populations, as these groups may be denied access to understanding how health interventions work for them in clinical settings? Second, are groups considered vulnerable in traditional clinical trials also vulnerable in pragmatic clinical trials? We argue first that excluding vulnerable subjects from participation in pragmatic clinical trials can be harmful by preventing acquisition of data to meaningfully inform clinical decision-making in the future. Second, we argue that protections for vulnerable subjects in traditional clinical trial settings may not be translatable, feasible, or even ethical to apply in pragmatic clinical trials. We conclude by offering specific recommendations for appropriately protecting vulnerable research subjects in pragmatic clinical trials, focusing on pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons.

Several requirements and regulations have been issued to promote clinical trial transparency through prospective registration of trials, disclosure of results, access to trial reports submitted to regulatory agencies and access to anonymised patient-level data. -Clinical trial results are disseminated through articles. Yet, many present outcome reporting bias. -Open-access to trial data will help to deter outcome reporting bias. However, this is not enough to clinicians

Life expectancy statistics predict that in a couple of decades women will enjoy a mean life of 90 years. Assuming a median age for the onset of menopause of 51, women will spend about 40 years in menopause. Harvesting and freezing ovarian cortical tissue at a younger age to permit future transplantation for postponing menopause and its sequelae could become a possible option. However, both medical and ethical issues need to be addressed before this can be offered as a treatment for menopause.

BACKGROUND: Unilateral Do-Not-Resuscitate (DNR) orders (against patient/family wishes) have been ethically justified in cases of medical futility. We investigated whether electrophysiology practitioners believe medical futility justifies unilateral ICD deactivation. METHODS AND RESULTS: Email invitations to take an online survey were sent to 1,894 EP practitioners. 384 responses were collected (response rate 20.6%). Though the sample included respondents from Europe, Asia, Australia, South American and Africa, the majority were from North American (78%), were academically affiliated (64%) and practiced in an urban setting (67.8%). Deactivation of ICD shock function in agreement with patient wishes and a pre-existing DNR was not considered physician assisted suicide (93.2%, 358/384). However, a majority of the sample responded that it was not ethical/moral for doctors to deactivate ICDs against patients' wishes (77.1%, 296/384) or against family/surrogates' wishes (72.4%, 278/384), even in the context of medical futility. A majority indicated that deactivating ICD shock function is not ethically/morally different than withholding CPR or external defibrillation in a code (72.7%, 277/381) but was different than deactivating pacing in a pacemaker-dependent patient (82.8%, 318/384). In the classification of interventions, a plurality (43.0%, 165/383) regarded ICD's to be unlike any other intervention. Concerning pacemakers, 50% (191/382) considered them to be like dialysis (a therapy which keeps patients alive). CONCLUSIONS: This international sample of electrophysiology practitioners considered ICD and pacemaker deactivation to be ethically distinct. While ICD deactivation was considered appropriate in the setting of patient/family agreement, unilateral deactivation was not

Whistleblowers remain essential as complainants in allegations of research misconduct. Frequently internal to the research team, they are poorly protected from acts of retribution, which may deter the reporting of misconduct. In order to perform their important role, whistleblowers must be treated fairly. Draft regulations for whistleblower protection were published for public comment almost a decade ago but never issued (Dahlberg 2013). In the face of the growing challenge of research fraud, we suggest vigorous steps, to include: organizational responsibility to certify the accuracy of research including audit, required whistleblower action in the face of imminent or grave harm to subjects, strengthened legal protections against retaliation including prompt enactment of Federal whistleblower protections and consideration of criminalizing the most egregious cases of research misconduct.

Since the early 1970s, the ethical norm governing counselors involved in testing and screening for genetic conditions related to reproduction has been strict neutrality. Counseling about reproductive genetics was to be patient centered but nondirective. Many advocates for people with Down syndrome believe that high abortion rates following a diagnosis of this condition show an unfounded bias against those with Down syndrome. These advocates have succeeded in enacting federal and state legislation that requires women who receive a prenatal diagnosis of Down syndrome to receive positive information about the condition, thereby ending the nominal goal of value-neutral counseling and setting the stage for further normative shifts in clinical reproductive genetics as counseling expands because of cell-free testing.