Considerations for applying bioethics norms to a biopharmaceutical industry setting.

Background: The biopharmaceutical industry operates at the intersection of life sciences, clinical research, clinical care, public health, and business, which presents distinct operational and ethical challenges. This setting merits focused bioethics consideration to complement legal compliance and business ethics efforts. However, bioethics as applied to a biopharmaceutical industry setting often is construed either too broadly or too narrowly with little examination of its proper scope.

Clinical use of amyloid-positron emission tomography neuroimaging: Practical and bioethical considerations.

Until recently, estimation of β-amyloid plaque density as a key element for identifying Alzheimer's disease (AD) pathology as the cause of cognitive impairment was only possible at autopsy. Now with amyloid-positron emission tomography (amyloid-PET) neuroimaging, this AD hallmark can be detected antemortem. Practitioners and patients need to better understand potential diagnostic benefits and limitations of amyloid-PET and the complex practical, ethical, and social implications surrounding this new technology.

Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees.

A novel Protocol Ethics Tool Kit ('Ethics Tool Kit') has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews.

A Pharmaceutical Bioethics Consultation Service: Six-Year Descriptive Characteristics and Results of a Feedback Survey.

: Bioethics consultations are conducted in varied settings, including hospitals, universities, and other research institutions, but there is sparse information about bioethics consultations conducted in corporate settings such as pharmaceutical companies. The purpose of this article is to describe a bioethics consultation service at a pharmaceutical company, to report characteristics of consultations completed by the service over a 6-year period, and to share results of a consultation feedback survey. : Data on the descriptive characteristics of bioethics consultations were collected from 2008 to 2013 and analyzed in Excel 2007.

Eli Lilly and Company's bioethics framework for human biomedical research.

Current ethics and good clinical practice guidelines address various aspects of pharmaceutical research and development, but do not comprehensively address the bioethical responsibilities of sponsors. To fill this void, in 2010 Eli Lilly and Company developed and implemented a Bioethics Framework for Human Biomedical Research to guide ethical decisions. (See our companion article that describes how the framework was developed and implemented and provides a critique of its usefulness and limitations.

Development, implementation and critique of a bioethics framework for pharmaceutical sponsors of human biomedical research.

Pharmaceutical human biomedical research is a multi-dimensional endeavor that requires collaboration among many parties, including those who sponsor, conduct, participate in, or stand to benefit from the research. Human subjects' protections have been promulgated to ensure that the benefits of such research are accomplished with respect for and minimal risk to individual research participants, and with an overall sense of fairness. Although these protections are foundational to clinical research, most ethics guidance primarily highlights the responsibilities of investigators and ethics review boards.

Expanded Access Programs: Ethical and Practical Considerations for Biopharmaceutical Sponsors.

Expanded access is a regulatory mechanism by which an investigational drug can be made available outside of a clinical trial to treat patients with serious or life-threatening conditions for which there are no satisfactory treatment options. An expanded access program (EAP) is the formal plan under which preapproval access to an investigational drug can be provided to a group of patients. Although an EAP is a regulated program, the decision to authorize an EAP is the responsibility of the biopharmaceutical sponsor.

Developing good scientific publishing practices: one pharmaceutical company's perspective.

Background: The scientific publishing practices of the pharmaceutical industry have been heavily criticized in recent years due to the inherent conflict of interest that arises when a pharmaceutical company publishes findings around its own drugs.

Scope: Eli Lilly and Company ('Lilly') strives for transparency in its day-to-day activities, and, here, shares its principles, policies and practices on publishing "Lilly-sponsored" research.

Findings: A conflict of interest does not necessarily equate to biased presentation of research findings, and operating a successful, for-profit business and maintaining a focus on improving the health of patients are not mutually exclusive goals.

Onset of antidepressant effect of olanzapine and olanzapine/fluoxetine combination in bipolar depression.

Objectives: The current analysis investigated the onset of antidepressant effect of olanzapine/fluoxetine combination.

Methods: Data for these post hoc analyses were obtained from a clinical trial comparing olanzapine, placebo, and olanzapine/fluoxetine combination in bipolar depression (BD). Subjects were 833 patients with a DSM-IV diagnosis of bipolar I disorder, depressed.

Glucose-insulin-potassium echocardiography detects improved segmental myocardial function and viable tissue shortly after acute myocardial infarction.

Previous studies showed that glucose-insulin-potassium (GIK) increases cardiac output in patients after cardiac surgery and improves segmental myocardial wall motion. We hypothesized that GIK improves regional wall motion, detects contractile reserve, and predicts functional recovery at follow-up to a similar extent as low-dose dobutamine (LDD) in patients with recent myocardial infarction. Forty-one patients underwent LDD and GIK echocardiography.

Olanzapine/fluoxetine combination for treatment-resistant depression: a controlled study of SSRI and nortriptyline resistance.

Background: This 8-week, double-blind, multicenter study was undertaken to replicate, in a larger sample of patients with treatment-resistant major depressive disorder (MDD; DSM-IV criteria), the results of a pilot study of the olanzapine/fluoxetine combination.

Method: The study was begun in August 1999. The primary entry criterion was a history of failure to respond to a selective serotonin reuptake inhibitor (SSRI).

Ototoxic occupational exposures for a stock car racing team: I. Noise surveys.

The National Institute for Occupational Safety and Health (NIOSH) surveyed noise exposure for a professional stock car team at their race shop and during two races at one racetrack. At the team's shop, area sound pressure levels (SPLs) were measured for various work tasks. Equivalent levels (Leqs) ranged from 58 to 104 decibels, A-weighted (dBA).

Ototoxic occupational exposures for a stock car racing team: II. chemical surveys.

The National Institute for Occupational Safety and Health (NIOSH) conducted a series of surveys to evaluate occupational exposure to noise and potentially ototoxic chemical agents among members of a professional stock car racing team. Exposure assessments included site visits to the team's race shop and a worst-case scenario racetrack. During site visits to the race team's shop, area samples were collected to measure exposures to potentially ototoxic chemicals, including, organic compounds (typical of solvents), metals, and carbon monoxide (CO).

Long-term follow-up of patients with refractory heart failure and myocardial ischemia treated with cardiac resynchronization therapy.

Studies in patients without coronary artery disease have shown the restoration of glucose metabolism by cardiac resynchronization therapy (CRT) without changes in myocardial perfusion. We report on the long-term outcome of CRT in 24 patients with severe heart failure (HF) and advanced coronary artery disease not amenable for revascularization. All patients had documented myocardial ischemia on stress (99)Tc-sestamibi single-photon emission computed tomography, and all underwent successful implantations of CRT systems.

Noninvasive mapping of left ventricular electromechanical asynchrony by three-dimensional echocardiography and semi-automatic contour detection.

A system for analyzing left ventricular (LV) electromechanical asynchrony based on transesophageal 3-dimensional echocardiography (3-DE) and semi-automatic endocardial contour detection is described. Eighteen consecutive patients underwent 3-DE. Using TomTec 4DLV software, a 3-dimensional endocardial surface was reconstructed throughout the cardiac cycle.

Effects of cardiac resynchronization therapy on myocardial perfusion reserve.

Background: Cardiac resynchronization therapy (CRT) is a relatively new treatment strategy for patients with heart failure and mechanical asynchrony. Reported effects of CRT on regional myocardial blood flow (MBF) are conflicting, and effects on hyperemic MBF are scarce. The aim of the present study was to assess serial changes of MBF and MBF reserve in patients receiving a biventricular pacemaker.

Perfusable tissue index as a potential marker of fibrosis in patients with idiopathic dilated cardiomyopathy.

Unlabelled: A varying degree of interstitial and perivascular fibrosis is a common finding in idiopathic dilated cardiomyopathy (DCM). The perfusable tissue index (PTI), obtained with PET, is a noninvasive tool for assessing myocardial fibrosis on a regional level. Measurements of the PTI in DCM, however, have not been performed yet.

A double-blind, randomized study of olanzapine and olanzapine/fluoxetine combination for major depression with psychotic features.

The purpose of this study was to compare the efficacy and safety of olanzapine (OLZ) monotherapy and an olanzapine/fluoxetine combination (OFC) with placebo (PLA) for unipolar major depression with psychotic features. Under a single protocol, two 8-week, double-blind trials were conducted at 27 sites. Patients (n = 124 trial 1, n = 125 trial 2) were randomized to 1 of 3 treatment groups: OLZ (5 to 20 mg/d), PLA, or OFC (olanzapine 5 to 20 mg/d + fluoxetine 20 to 80 mg/d).

Long-term antidepressant efficacy and safety of olanzapine/fluoxetine combination: a 76-week open-label study.

Background: The olanzapine/fluoxetine combination has demonstrated effectiveness in treatment-resistant depression (TRD). Although this combination is being used by prescribers, this is the first study to examine long-term use. Long-term efficacy and safety were therefore investigated in a group of patients with major depressive disorder (MDD) with and without TRD.

Usefulness of a new active-fixation lead in transvenous temporary pacing from the femoral approach.

Temporary transvenous pacing is associated with a high incidence of complications with a substantial dislocation rate reported to occur in more than one-third of patients. This article describes a novel 3.5 Fr temporary pacing lead using active fixation in a consecutive series of 42 patients with prolonged (> or = 48 hours) temporary pacing.

The effect of rate responsive pacing in patients with angina pectoris on the extent of ischemia on 201-thallium exercise scintigraphy.

In patients with coronary artery disease (CAD), rate responsive pacing is considered to be contraindicated because an increase in heart rate may increase oxygen demand. Although previous studies have shown no subjective increase in ischemia during rate responsive pacing, data from objective assessment have not been documented. The goal of this study was to determine if there was an increase in ischemia on 201-Thallium (201 Tl) exercise scintigraphy in this mode of pacing in patients with CAD and angina.

Oxidative DNA damage is associated with intense noise exposure in the rat.

Increasing evidence suggests that noise-induced hearing loss may be reduced or prevented with antioxidant therapy. Biochemical markers of reactive oxygen species (ROS)-induced damage can help elucidate possible treatment timing constraints. This study examined the time course of ROS damage following a 2-h, broad-band noise exposure resulting in permanent threshold shift in 35 Long-Evans rats.

Pacing-induced left ventricular dysfunction. Relationship with coronary perfusion.

In a patient admitted with symptomatic complete heart block, a DDD pacemaker was implanted. Prior to implantation, echocardiography showed normal left ventricular function. Shortly after implantation, acute congestive heart failure developed with extensive regional hypo- and akinetic segments in the anteroseptal, anterolateral and apical region.

Electromagnetic interference of an implantable loop recorder by commonly encountered electronic devices.

Electromagnetic interference of pacemaker systems has been well established and can lead to an inappropriate function of these devices. Recently, an implantable loop recorder (ILR) (REVEAL, Medtronic Inc.) has been introduced to evaluate the possible arrhythmic etiology of patients with recurrent syncope.

Usefulness of echocardiography to predict inappropriate atrial sensing in single-lead VDD pacing.

Reliable atrial sensing is the prerequisite for restoration of atrioventricular synchrony in patients with single-lead VDD pacing systems. To determine echocardiographic variables associated with inappropriate atrial sensing, 21 consecutive patients with symptomatic second- or third-degree AV block and normal sinus node function were studied. Prior to implantation echocardiographic measurements of end-systolic and end-diastolic dimensions and volumes of the right atrium and right ventricle were performed.