Managing conflicts of interest: a survival guide for biotechs

Conflicts of interest in research can affect a company's ability to move a product through the approval processor attract investment. Avoid the pitfalls by taking pro-active steps to manage these risks.     

Genetic conflicts of interest in plants

Several features of the reproductive biology of seed plants have recently been explained using kin-selection interpretations. The simultaneous presence of tissues with different genetic make-ups during several phases of a seed-plant's life cycle is a feature that sets the conditions for agonistic interactions among selfish genes. The available empirical evidence indicates that genetic conflicts of interest are prevalent phenomena in seed plants. Recent research on the patterns of endosperm gene transmission provides a framework for new interpretations of the role of inclusive fitness in plants.     

Hazards from chemicals: scientific questions and conflicts of interest.

All substances are toxic when the dose is large enough. In order to regulate the use of chemicals, we need to measure the level at which toxic effects are found. Epidemiological evidence suggests that present levels of chemical use do not lead to widespread harmful contamination of the human environment. For chemicals, most of the problems of toxicity are found in the workplace, while the population at large gets most of its toxic effects from voluntary exposure to substances such as tobacco smoke and ethanol. The prevention and control of toxic effects depends on a series of steps. This begins with measurement of toxicity in model systems, such as laboratory animals, and the estimation of the likely exposure of workers or consumers. Reliable extrapolation of information gathered from animals to the diverse and biochemically differing human population depends on understanding mechanisms of toxic effects. The toxic effect and mechanisms of action of substances such as carbon tetrachloride or paracetamol have been extensively investigated, and our ability to predict toxicity or develop antidotes to poisoning has had some success, but epidemiology is still an essential part of assessment of toxic effects of new chemicals. The example of phenobarbitone shows how animal experiments may well lead to conclusions which do not apply to man. After measurement of toxicity and assessment of likely hazards in use comes the final evaluation of the use of a chemical. This depends not only on its toxicity, but also on its usefulness. The direct effects on health may be small in comparison with the indirect advantageous effects which a useful substance such as vinyl chloride may bring. The assessment of risks and benefits of new chemicals can be partly removed from a political style of discourse, but the evaluation of the relative weight to be attached to these risks and benefits is inescapably political. The scientific contribution must be to allow the debate to take place in the light of maximum clarity of information about the consequences of use of chemicals.     

Investigator experiences with financial conflicts of interest in clinical trials

Background

Sub-threshold depression is common, impairs functioning, and increases the risk of developing major depression. Although psychological treatments have been investigated for sub-threshold depression, they are costly. A less costly alternative could be an educational health promotion campaign about effective self-help for depression symptoms. The aim of the study is to test the efficacy of a low-cost email-based mental health promotion campaign in changing self-help behaviour and preventing more severe depression in adults with sub-threshold depression.

Methods/Design

The project is a randomised controlled trial of an automated preventive email-intervention aimed at people with sub-threshold depression. Adults aged 18+ with sub-threshold depression (as measured with the Patient Health Questionnaire-9), who are not already receiving professional treatment for depression, are eligible for admission to the study. Internet users will sign up via the study website http://www.moodmemos.com and be randomly allocated to receive emails twice weekly for six weeks containing either self-help coping advice or general information about depression as a control. Outcomes will be assessed at the start, midpoint, and end of the intervention, as well as six months later. Outcomes assessed include symptoms, incidence of major depression, psychological distress, social and occupational functioning, coping strategies, and coping self-efficacy. The primary hypothesis is that the Mood Memo emails containing coping strategies will reduce depression symptoms and be better at preventing major depression than the control emails that contain general information about depression.

Discussion

Promotion of actions an individual can take to prevent physical disease is a technique often used in public health. This study applies this approach to mental health, and explores whether a low-cost, easily disseminated email-based campaign can improve self-help coping behaviour and prevent depression in adults with sub-threshold depression.

Trial Registration

Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12609000925246     

Trade-offs, conflicts of interest and manipulation in Plasmodium-mosquito interactions

A long-held view among parasitologists is that infection by malaria parasites does not harm the mosquito vector. One of the reasons for this belief is that the two partners of the association share interests in the most important life-history traits of the mosquito. Both partners benefit from increased survival and an increased rate of bloodfeeding the mosquito to increase its reproductive success and the parasite to ensure its transmission. Problems with this line of reasoning appear when one considers possible trade-offs among the mosquito's life-history parameters, which constrain the attempts by the mosquito and the parasite to maximize their success. Could these constraints differ between the two partners and thus lead to conflicts of interest and what would be the evolutionary and epidemiological consequences of conflicting interests? These questions will be investigated below.     

Reporting science and conflicts of interest in the lay press

Background

Forthright reporting of financial ties and conflicts of interest of researchers is associated with public trust in and esteem for the scientific enterprise.

Methods/Principal Findings

We searched Lexis/Nexis Academic News for the top news stories in science published in 2004 and 2005. We conducted a content analysis of 1152 newspaper stories. Funders of the research were identified in 38% of stories, financial ties of the researchers were reported in 11% of stories, and 5% reported financial ties of sources quoted. Of 73 stories not reporting on financial ties, 27% had financial ties publicly disclosed in scholarly journals.

Conclusions/Significance

Because science journalists often did not report conflict of interest information, adherence to gold-standard recommendations for science journalism was low. Journalists work under many different constraints, but nonetheless news reports of scientific research were incomplete, potentially eroding public trust in science.     

Small-sized neurons of trigeminal ganglia express multiple voltage-sensitive calcium channels: a qualitative immunohistochemical study

The cell bodies of pseudounipolar neurons of the trigeminal ganglia have been presumed to play a supportive role to neurites, which transmit various sensations like pain from the periphery to the brain stem. However, several studies have recently shown that these neuronal cell bodies could modulate the afferent stimuli by up-regulating various ion channels and also by increasing the synthesis of neuropeptides like calcitonin gene-related peptide (CGRP). Since voltage-sensitive calcium ion channels (VSCCs) determine neuropeptides/neurotransmitters released by neurons, the aim of the present study was to localize the various VSCCs (N-, P/Q-, L-, T- and R-types) in the trigeminal ganglia neurons by immunohistochemistry. The results showed that all the VSCCs are expressed by the cell bodies of neurons though the small-sized neurons showed higher expression of these channels. The small-sized neurons were identified by immunohistochemical localization of CGRP, the most common neuropeptide for pain transmission in the trigeminal ganglia neurons. Some of these channels (N, P/Q and T types) were also expressed on the cell surface though previous electrophysiological studies have shown the expression of all the channels on the cell surface. It is suggested that the cell bodies could play a more active role than hereto ascribed to these, in the modulation of sensory stimuli.     

Regulation of financial conflicts of interest in medical practice and medical research: a damaging solution in search of a problem

The free market, which includes most practicing physicians, publicly supported biomedical researchers, and private drug and device companies, has succeeded spectacularly in delivering new medical technologies to the public. Increased interactions between doctors (physicians and biomedical researchers), epitomized by the founding of the biotechnology revolution, have and can continue to accelerate this delivery. A powerful anti-commercial advocacy movement that has blossomed over the past 20 years threatens this momentum. This movement has succeeded in inverting reality by demonizing the market and by promoting distorted and damaging views of professionalism and of science. Most ominously, it has imposed onerous and counterproductive regulations on medical education and translational research.     

Hymenopteran wing kinematics: a qualitative study

(With 9 plates and 2 figures in the text)
Wing deformations were studied in representatives of several hymenopteran families during free Right in hovering or near hovering conditions. The claval furrow, costal break, stigma and a variety of flexion lines occupying the wing apex are all involved in regulating forewing profile during the flight cycle in lchneumonidae and Tenthredinidae. In these families, as well as in the sphecid Sphex rujocincius , the median flexion line of the hindwing is also active in the terminal stages of supination. The plaiting fold of the vespid forewing plays an important role in profile control during the upstroke, reversing its polarity compared to rest. Little wing distortion was observed in the large scolids Scotia flavifrons and S. hirta , possibly attributable to the presence of strengthening ridges and grooves in the wing apex.     

Patients' experiences with partial dentures: a qualitative study

Objective: The aim of the study was to gain insight into people's experiences of being given and using partial dentures. Methods: In‐depth semi‐structured interviews were carried out with 23 people of varied age, social background and denture wearing experience in Tayside, Scotland. Participants were encouraged to discuss how they came to have partial dentures, their day‐to‐day denture use and their interactions with dentists. The interview data were systematically coded using key theme headings, and summary charts were constructed to facilitate analysis. Results: The initial decision that a partial denture was needed was generally difficult to accept. People perceived the main benefits of partial dentures to be improved appearance and confidence, but experienced a variety of difficulties with their dentures and often coped with these by only wearing them on social occasions. Participants had not always told their dentists about the difficulties they experienced. Barriers to seeking help with denture problems included financial constraints, previous experience of rushed appointments or poor communication from dentists and a perceived lack of entitlement to help when partial dentures were issued free. Conclusions: Partial dentures can be difficult to cope with. People experience a range of difficulties in wearing them, not all of which have been discussed with dentists. Informative and supportive communication when partial dentures are first needed, and subsequently, can improve the quality of patients’ experiences and may help promote effective use and appropriate help‐seeking by partial denture wearers.     

Quantitative and qualitative automatic evaluation of afterdischarges in the study of antiepileptic drugs

An automatic analysis of bioelectrical activity in some structures of the rabbit's brain was performed after i.v. administration of diazepam, phenytoin or phenobarbital. It was found that diazepam raised the ratio of fast activity in the afterdischarges pattern but paralelly decreased the total energy involved in the production of after-discharges in the cortex and midbrain reticular formation. Phenobarbital caused a significant shift in frequencies, increasing the ratio of slow activities (in the exception of hippocampus) and decreased the power spectra of afterdischarges in all structures (in the exception of midbrain reticular formation). Phenytoin, similarly to phenobarbital, decreased the ratio of fast activities. This effect was significant only in thalamus and midbrain reticular formation. At the same time it increased the total power of signal from hippocampus and midbrain reticular formation.     

Barriers to partnership working in public health: a qualitative study

Background

Public health provision in England is undergoing dramatic changes. Currently established partnerships are thus likely to be significantly disrupted by the radical reforms outlined in the Public Health White Paper. We therefore explored the process of partnership working in public health, in order to better understand the potential opportunities and threats associated with the proposed changes.

Methodology/Principal Findings

70 participants took part in an in-depth qualitative study involving 40 semi-structured interviews and three focus group discussions. Participants were senior and middle grade public health decision makers working in Primary Care Trusts, Local Authorities, Department of Health, academia, General Practice and Hospital Trusts and the third sector in England. Despite mature arrangements for partnership working in many areas, and much support for joint working in principle, many important barriers exist. These include cultural issues such as a lack of shared values and language, the inherent complexity of intersectoral collaboration for public health, and macro issues including political and resource constraints. There is particular uncertainty and anxiety about the future of joint working relating to the availability and distribution of scarce and diminishing financial resources. There is also the concern that existing effective collaborative networks may be completely disrupted as the proposed changes unfold. The extent to which the proposed reforms might mitigate or potentiate these issues remains unclear. However the threats currently remain more salient than opportunities.

Conclusions

The current re-organisation of public health offers real opportunity to address some of the barriers to partnership working identified in this study. However, significant threats exist. These include the breakup of established networks, and the risk of cost cutting on effective public health interventions.     

The views of singlehanded general practitioners: a qualitative study.

OBJECTIVES--To examine the concerns of singlehanded general practitioners working in an inner London area and to compare the views of general practitioners in partnerships. DESIGN--Qualitative analysis of semistructured interviews with a random sample of singlehanded general practitioners and a sample of general practitioners from partnerships matched for age and sex. SETTING--The area covered by Lambeth, Southwark, and Lewisham Family Health Services Authority. RESULTS--The singlehanded general practitioners were more likely to be older, male, and first qualified abroad than general practitioners in partnerships. Their major concerns were inadequate premises, maintaining their singlehanded status, and coping with recent changes to their contract. Most were very satisfied with their solo status and did not see the provision of 24 hour care as stressful. CONCLUSION--Singlehanded general practitioners saw themselves as providing a unique service for patients, and their status as an alternative for general practitioners who were unhappy in partnerships. Such practices are unlikely to wither away as a pattern of provision. Any comprehensive development of primary care must take their needs into account.