Tripartite conflicts of interest and high stakes patent extensions in the DSM-5.

BACKGROUND: The revision process for and recent publication of the DSM-5 initiated debates about the widening of diagnostic boundaries. The pharmaceutical industry had a major financial stake in the outcome of these debates. This study examines the three-part relationship among DSM panel members, principal investigators (PIs) of clinical trials for new DSM-5 diagnoses, and drug companies. METHODS: Financial conflicts of interest (FCOI) of DSM panel members responsible for some new diagnoses in the DSM-5 and PIs of clinical trials for related drug treatments were identified. Trials were found by searching ClinicalTrials.gov. Patent and revenue information about these drugs was found using the US Food and Drug Administration's Orange Book and manufacturer Annual Reports. RESULTS: Thirteen trials met inclusion criteria (testing drugs for some new DSM disorders). Sixty-one percent of the DSM Task Force members and 27% of Work Group members reported FCOI to the trial drug manufacturers. In 5 of the 13 trials (38%), PIs reported ties other than research funding to the drug manufacturer. In 3 of the trials (23%), a PI had financial ties to the drug manufacturer and was also a DSM panel member who had decision-making authority over the revision process. CONCLUSIONS: These findings suggest that increased transparency (e.g., registration on ClinicalTrials.gov) and mandatory disclosure policies (e.g., the American Psychiatric Association's disclosure policy for DSM-5 panel members) alone may not be robust enough strategies to prevent the appearance of bias in both the DSM revision process as well as clinical decisions about appropriate interventions for DSM disorders.

Conflict of Interest Policies and Industry Relationships of Guideline Development Group Members: A Cross-Sectional Study of Clinical Practice Guidelines for Depression.

Because of increased attention to the issue of trustworthiness of clinical practice guidelines, it may be that both transparency and management of industry associations of guideline development groups (GDGs) have improved. The purpose of the present study was to assess a) the disclosure requirements of GDGs in a cross-section of guidelines for major depression; and, b) the extent and type of conflicts of panel members. Treatment guidelines for major depression were identified and searched for conflict of interest policies and disclosure statements. Multi-modal screens for undeclared conflicts were also conducted. Fourteen guidelines with a total of 172 panel members were included in the analysis. Eleven of the 14 guidelines (78%) had a stated conflict of interest policy or disclosure statement, although the policies varied widely. Most (57%) of the guidelines were developed by panels that had members with industry financial ties to drug companies that manufacture antidepressant medication. However, only a minority of total panel members (18%) had such conflicts of interest. Drug company speakers bureau participation was the most common type of conflict. Although some progress has been made, organizations that develop guidelines should continue to work toward greater transparency and minimization of financial conflicts of interest.

Drug firms, the codification of diagnostic categories, and bias in clinical guidelines.

The possibility that industry is exerting an undue influence on the culture of medicine has profound implications for the profession's public health mission. Policy analysts, investigative journalists, researchers, and clinicians have questioned whether academic-industry relationships have had a corrupting effect on evidence-based medicine. Psychiatry has been at the heart of this epistemic and ethical crisis in medicine. This article examines how commercial entities, such as pharmaceutical companies, influence psychiatric taxonomy and treatment guidelines. Using the conceptual framework of institutional corruption, we show that organized psychiatry's dependence on drug firms has led to a distortion of science. We describe the current dependency corruption and argue that transparency alone is not a solution. We conclude by taking the position that the corruption of the evidence base in diagnostic and practice guidelines has compromised the informed consent process, and we suggest strategies to address this problem.

Idiosyncratic variables that affect functional analysis outcomes: a review (2001-2010).

Although typical functional analyses often produce clear outcomes, some studies have reported ambiguous results that cannot be interpreted. Such undifferentiated outcomes may occur if test conditions do not include relevant antecedent or consequent events. Clinicians then may try to modify the functional analysis conditions to include those events. Hanley, Iwata, and McCord (2003) reviewed the functional analysis literature through 2000 and described idiosyncratic variables included in modified functional analyses. The objective of the present review was to present a quantitative analysis of idiosyncratic antecedents and consequences in modified functional analyses during the past decade (2001 to 2010). We discuss the range of stimulus parameters tested and the assessment strategies used for informing the modified analysis conditions.

Conflicts of interest and the quality of recommendations in clinical guidelines.

BACKGROUND: There is increasing concern that conflicts of interest affect the development process of clinical practice guidelines. We evaluated The American Psychiatric Association's Practice Guideline for the Treatment of Patients with Major Depressive Disorder to determine the existence of financial and intellectual conflicts of interest and examine their possible effects. We selected this guideline because of its influence on clinical practice and because this guideline recommends pharmacotherapy for all levels of depression, despite controversies over the evidence base. METHODS AND FINDINGS: We determined the number and type of financial conflicts of interest for members of the guideline development group as well as for the independent panel charged with mitigating any effect of these conflicts. We also quantified the potential for intellectual conflicts of interest. We examined the quality of references used to support recommendations, as well as the degree of congruence between the research results and the recommendations. Fewer than half (44.4%) of the studies supporting the recommendations met criteria for high quality. Over one-third (34.2%) of the cited research did not study outpatients with major depressive disorder, and 17.2% did not measure clinically relevant results. One-fifth (19.7%) of the references were not congruent with the recommendations. Financial ties to industry were disclosed by all members (100%) of the guideline development committee with members reporting a mean 20.5 relationships (range 9-33). The majority of the committee participated on pharmaceutical companies' speakers' bureaus. Members of the independent panel that reviewed the guidelines for bias had undeclared financial relationships. As a marker of intellectual conflict of interest, 9.1% of all cited research and 13% of references supporting the recommendations were co-authored by the six guideline developers. CONCLUSIONS: The prevalence of conflicts of interest among panel members was high. The quality of the evidence cited raises questions about the validity of the recommendations. Attention to the quality of cited studies and to the risk of bias resulting from conflicts of interest should be a priority for guideline development groups.

Dynamic informed consent processes vital for treatment with antidepressants.

Advances in technology and transparency have greatly accelerated the ability of clinicians to remain current with regards to being informed and informing patients about the risk/benefit ratio when considering antidepressant medication. In spite of this, the current climate of pharmaceutical industry influence on medical practice does much to hinder informed consent processes. Recent findings of previously unknown and potentially dangerous adverse effects of the second- and third-generation classes of antidepressants underscore the importance of enhancing the practice of informed consent. After considering the concept of informed consent as it has evolved over time, the authors summarize some of the newer side effects associated with second- and third-generation antidepressants and then move on to describe impediments in the way of achieving adequate informed consent at the clinical encounter. Among these impediments, the authors discuss the impact of industry influence, cognitive bias in decision-making, and time constraints. These obstacles and the notion that modern antidepressants are not as safe as once thought offer an opportunity to revisit the process of informed consent. A dynamic concept of informed consent is proposed with the acknowledgement that a mere listing of side effects or pro forma approach to informed consent is inadequate, and that a mindful and ongoing dialog with patients in which clinicians are responsive to patients' evolving needs as new information becomes available will more likely result in patient empowerment and a strengthening of the therapeutic alliance, thereby allowing patient and doctor to shoulder the burden of uncertainty together and leading to more optimal treatment outcomes.

Resistance to disruption in a classroom setting.

Substantial experimental evidence indicates that behavior reinforced on a denser schedule is more resistant to disruption than is behavior reinforced on a thinner schedule. The present experiment studied resistance to disruption in a natural educational environment. Responding during familiar activities was reinforced on a multiple variable-interval (VI) 7-s VI 30-s schedule for 6 participants with developmental disabilities. Resistance to disruption was measured by presenting a distracting item. Response rates in the disruption components were compared to within-session response rates in prior baseline components. Results were consistent with the predictions of behavioral momentum theory for 5 of 6 participants.

Observing behavior and atypically restricted stimulus control.

Restricted stimulus control refers to discrimination learning with atypical limitations in the range of controlling stimuli or stimulus features. In the study reported here, 4 normally capable individuals and 10 individuals with intellectual disabilities (ID) performed two-sample delayed matching to sample. Sample-stimulus observing was recorded with an eye-tracking apparatus. High accuracy scores indicated stimulus control by both sample stimuli for the 4 nondisabled participants and 4 participants with ID, and eye tracking data showed reliable observing of all stimuli. Intermediate accuracy scores indicated restricted stimulus control for the remaining 6 participants. Their eye-tracking data showed that errors were related to failures to observe sample stimuli and relatively brief observing durations. Five of these participants were then given interventions designed to improve observing behavior. For 4 participants, the interventions resulted initially in elimination of observing failures, increased observing durations, and increased accuracy. For 2 of these participants, contingencies sufficient to maintain adequate observing were not always sufficient to maintain high accuracy; subsequent procedure modifications restored it, however. For the 5th participant, initial improvements in observing were not accompanied by improved accuracy, an apparent instance of observing without attending; accuracy improved only after an additional intervention that imposed contingencies on observing behavior. Thus, interventions that control observing behavior seem necessary but may not always be sufficient for the remediation of restricted stimulus control.