Competing interests: The need to control conflict of interests in biomedical research

Individual and institutional conflict of interests in biomedical research have becomes matters of increasing concern in recent years. In the United States, the growth in relationships — sponsored research agreements, consultancies, memberships on boards, licensing agreements, and equity ownership — between for-profit corporations and research universities and their scientists has made the problem of conflicts, particularly financial conflicts, more acute. Conflicts can interfere with or compromise important principles and obligations of researchers and their institutions, e.g., adherence to accepted research norms, duty of care to patients, and open exchange of information. Disclosure is a key component of a successful conflict policy. Commitments which conflict with a faculty member's primary obligations to teaching, research, administrative responsibilities, or patient care also need attention. Institutional conflict of interests present different problems, some of which are discussed in an analysis of an actual problem posed by two proposed clinical trials. This paper is adapted from a lecture presented to a Symposium on Scientific Integrity, Warsaw, Poland, 23 November 1995. Daniel Steiner was Vice-President and General Counsel of Harvard University (1972–92) and in that capacity became familiar with conflict of interest issues. He is currently Counsel to the Boston law firm. Ropes and Gray, and is Adjunct Lecturer in Public Policy at the John F. Kennedy School of Government. Harvard University.     

The effects of massage velocity on heart rate and heart rate variability in healthy infants: A randomized crossover study

BackgroundInfant massage, in which mothers stroke their infant’s skin slowly and gently, can cause pleasant sensations in the infant that can be affected by the velocity of massage. However, the massage velocity at which infants feel the most pleasant sensations remains unclear.ObjectiveTo investigate the effects of massage velocity on heart rate (HR) and HR variability (HRV) in healthy infants.MethodTwenty-two infant-mother dyads two to seven months of age were recruited. Mothers stroked their infant’s skin at three massage velocities (5.0, 7.5, and 10.0 cm/s) in a randomized order for 15 min. The rhythm of massage velocity was calculated according to the length of three body areas. The massage velocity of the mothers was regulated using a metronome. HR and HRV (high frequency [HF] and low frequency [LF]) were measured at rest and during massage for each velocity. The effects on pleasantness were evaluated using percent change in median baseline value compared with median values for the three massage velocities. Statistical analysis was performed using analysis of variance mixed effect models to exclude “period” and “carryover” effects during massage.ResultsWhen measuring HF, massage (7.5 cm/s) caused a significant increase in pleasantness compared with 10.0 cm/s (p = 0.04). The HR and LF/HF ratio were not significantly changed between velocities.ConclusionResults of this study suggested that a massage velocity of 7.5 cm/s was the most pleasant for infants. Future research should investigate the relationship between an infant massage by optimal velocity and infant development in longitudinal studies.     

Cognitive-behavioral therapy for ADHD in medication-treated adults with continued symptoms

The purpose of the present study was to examine the potential efficacy, patient acceptability, and feasibility of a novel, cognitive-behavioral therapy (CBT) for adults with attention-deficit hyperactivity disorder (ADHD) who have been stabilized on medications but still show clinically significant symptoms. Thirty-one adults with ADHD and stable psychopharmacology for ADHD were randomized to CBT plus continued psychopharmacology or continued psychopharmacology alone. Assessments included ADHD severity and associated anxiety and depression rated by an independent evaluator (IE) and by self-report. At the outcome assessment, those who were randomized to CBT had lower IE-rated ADHD symptoms (p < .01) and global severity (p < .002), as well as self-reported ADHD symptoms (p < .0001) than those randomized to continued psychopharmacology alone. Those in the CBT group also had lower IE-rated and self-report anxiety (p's < .04), lower IE-rated depression (p < .01), and a trend to have lower self-reported depression (p = .06). CBT continued to show superiority over continued psychopharmacology alone when statistically controlling levels of depression in analyses of core ADHD symptoms. There were significantly more treatment responders among patients who received CBT (56%) compared to those who did not (13%) (p < .02). These data support the hypothesis that CBT for adults with ADHD with residual symptoms is a feasible, acceptable, and potentially efficacious next-step treatment approach, worthy of further testing.     

The Meaning vs. The Medical Model in the Empirically Supported Treatment Program: A Consideration of The Empirical Evidence

A review of the debate on the Empirically Supported Treatment Program is presented. It is argued that underlying the specifics of the debate are fundamentally incompatible paradigms: a meaning vs. a medical model. The findings from two gold standard multi-site studies are reviewed to conclude that the control condition meets requirements for an empirically supported treatment. The empirical finding of the failure of clinical training to improve treatment outcomes is explained by the focus on rational factors in training. It is recommended that training of therapists focus on enhancing experiential capacity rather than mastery of manualized treatment approaches.     

A call to restructure the drug development process: Government over-regulation and non-innovative late stage (Phase III) clinical trials are major obstacles to advances in health care

The history of drug/vaccine development has included major advances guided primarily by risk/benefit analyses concerning the innovative agent, not by evidence-based clinical trials (Phase I–IV). Because the approval for new drugs is hindered under the present process, the system requires restructuring. The Phase I/II study period should be more flexible, using the “environment of knowledge” about the new agent, plus risk/benefit assessments. Phase III, as presently constructed, does not add new adverse events data, it provides a narrower profile of drug efficacy than properly done Phase II studies, and placebo-controlled trials continue to raise unresolved ethical and social issues. Phase III studies should be abandoned for most drugs, and substituted with properly powered Phase II doseranging studies plus careful post-marketing surveillance. Phase III should be a penalty for poor drug development, not a regulatory requirement. To accomplish efficient drug development, greater cooperation between pharmaceutical companies and governments in developing clinical trials is needed rather than over-regulation. These changes will synchronize the drug development and regulatory process with the current rapid drug discovery process, reduce drug development time and cost, and improve patient care. The author is Adjunct Professor of Medicine, Weill Medical College of Cornell University, New York, New York, USA.     

Informed consent and the use of placebo in poland: Ethical and legal aspects

The concept of informed consent was one of the most fruitful ideas that deeply changed the relationships between physicians and their patients from paternalism to respect for the personal autonomy of subjects needing professional medical care. The great progress in medicine, also involving the pharmaceutical industry, has created an increasing need to perform different clinical and experimental trials. The evolution of clinical research in the last decades has influenced strongly the design of these studies. One of the most important changes in this field has been the use of placebo groups in double-blind controlled studies. The controversies have involved not only the use of placebo when standard or proven treatment was available, but also some specific problems concerning the procedure of obtaining informed consent in such trials. This paper briefly presents the evolution of informed consent in Poland as well as different ethical and legal problems concerning informed consent and the use of placebo controls in clinical trials. An earlier version of this paper was presented at an international conference, “Placebo: Its Action and Place in Health Research Today,” held in Warsaw, Poland on 12–13 April, 2003.     

The Ethics of Type 1 Diabetes Prediction and Prevention Research

There are approximately one million cases oftype 1 diabetes in the US, and the incidenceis increasing worldwide. Given that two-thirdsof cases present in childhood, it is criticalthat prediction and prevention research involvechildren. In this article, I examine whethercurrent research methodologies conform to theethical guidelines enumerated by the NationalCommission for the Protection of Human Subjectsof Biomedical and Behavioral Research, andadopted into the federal regulations thatprotect research subjects. I then offer twopolicy recommendations to help researchersdesign studies that conform to these ethicalrequirements.     

Effects of a meaningful, a discriminative, and a meaningless stimulus on equivalence class formation

Thirty college students attempted to form three 3-node 5-member equivalence classes under the simultaneous protocol. After concurrent training of AB, BC, CD, and DE relations, all probes used to assess the emergence of symmetrical, transitive, and equivalence relations were presented for two test blocks. When the A-E stimuli were all abstract shapes, none of 10 participants formed classes. When the A, B, D, and E stimuli were abstract shapes and the C stimuli were meaningful pictures, 8 of 10 participants formed classes. This high yield may reflect the expansion of existing classes that consist of the associates of the meaningful stimuli, rather than the formation of the ABCDE classes, per se. When the A-E stimuli were abstract shapes and the C stimuli became S(D)s prior to class formation, 5 out of 10 participants formed classes. Thus, the discriminative functions served by the meaningful stimuli can account for some of the enhancement of class formation produced by the inclusion of a meaningful stimulus as a class member. A sorting task, which provided a secondary measure of class formation, indicated the formation of all three classes when the emergent relations probes indicated the same outcome. In contrast, the sorting test indicated "partial" class formation when the emergent relations test indicated no class formation. Finally, the effects of nodal distance on the relatedness of stimuli in the equivalence classes were not influenced by the functions served by the C stimuli in the equivalence classes.     

An online hazard perception training course reduces heavy braking,speeding, and over-revving rates during everyday driving

In essence, driver training involves learning the skills required to drive safely and avoid dangerous events. However, in traditional on-road driver instruction, drivers virtually never accrue experience of the most significant types of events that they are learning to avoid: crashes. One means of providing this experience safely is to present novice drivers with video clips of real crashes, as part of structured learning exercises. A six-week automated online hazard perception training course for drivers, incorporating evidence-based training methods and over a hundred crash clips, was previously found to improve novice drivers’ hazard perception skill, which is known to be an important attribute for avoiding crashes. However, since hazard perception was measured using computer-based methods, the possibility remained that the training effect might not transfer to actual driving. We report a randomized control trial in which novice drivers were recruited to assess everyday driving behaviour objectively, using g-force triggered dashcams and GPS trackers installed in their vehicles. On-road data were collected for a one-month baseline period, and for a further two months after half of the sample completed the hazard perception training course. Drivers who completed the course significantly reduced their rate of heavy-braking events, their speeding behaviour, and their rate of over-revving events. These findings support the proposal that a relatively inexpensive and highly scalable hazard perception training intervention can improve on-road driving behaviour, with the clear potential to impact real-world driver safety.     

Treatment Effectiveness of PMTO for Children's Behavior Problems in Iceland: Child Outcomes in a Nationwide Randomized Controlled Trial

Well‐documented treatment methods must be tested following their implementation in community service agencies and across different cultures to ensure continuing effectiveness. This study was a randomized controlled trial (RCT) of Parent Management Training—the Oregon model (PMTO), conducted within a nationwide implementation in Iceland. Families of 102 clinically referred children with behavior problems were recruited from five municipalities throughout Iceland. Child age ranged from 5 to 12; 73% were boys. Families were randomly assigned to either PMTO or services usually offered in the communities (SAU). Child adjustment was measured with a latent construct based on parent, child, and teacher reports of externalizing and internalizing problems and social skills. Prepost intent‐to‐treat analyses showed that PMTO treatment led to greater reductions in child adjustment problems relative to the comparison group, obtaining a modest to medium effect size based on the construct score. Only one indicator (parent‐rated Social Skills) showed significant change independently and information on amount and kind of treatment in the SAU was limited. Overall, findings indicate that PMTO is an effective method to treat children's behavior problems in a Northern European culture and supply evidence for the method's successful implementation in community settings in Iceland. This is one of few nationwide implementation studies of PMTO outside the United States and the first RCT in Iceland to test a treatment model for children's behavior problems.