Erick H Turner

Oregon Health and Science University | OHSU · Department of Psychiatry

Background Valid assessment of drug efficacy and safety requires an evidence base free of reporting bias. Using trial reports in Food and Drug Administration (FDA) drug approval packages as a gold standard, we previously found that the published literature inflated the apparent efficacy of antidepressant drugs. The objective of the current study wa...

Objective To (1) investigate the extent to which recently published meta-analyses report trial funding, author–industry financial ties and author–industry employment from included randomised controlled trials (RCTs), comparing Cochrane and non-Cochrane meta-analyses; (2) examine characteristics of meta-analyses independently associated with reporti...

Background: A previous study found that 2 of 29 (6.9%) meta-analyses published in high-impact journals in 2009 reported included drug trials' funding sources, and none reported trial authors' financial conflicts of interest (FCOIs) or industry employment. It is not known if reporting has improved since 2009. Our objectives were to (1) investigate...

Background: A previous study found that 2 of 29 (6.9%) meta-analyses published in high-impact journals in 2009 reported included drug trials’ funding sources, and none reported trial authors’ financial conflicts of interest (FCOIs) or industry employment. It is not known if reporting has improved since 2009. Our objectives were to (1) investigate t...

(Reprinted with permission from Lancet 2018; 391:1357-66).

Background Previous studies on reporting bias generally examined whether trials were published in stand-alone publications. In this study, we investigated whether pooled-trials publications constitute a specific form of reporting bias. We assessed whether negative trials were more likely to be exclusively published in pooled-trials publications tha...

In medical research, a financial conflict of interest (FCOI) may affect the conduct and reporting of clinical trials.¹ The presence of FCOIs in clinical trials of oncology drugs that receive US Food and Drug Administration (FDA) approval is of particular concern, because these trials may change the trajectory of cancer care. These trials also gener...

Background: Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should...

Objective: We previously investigated the influence of reporting bias on the apparent proportion of statistically significant trials and effect size estimates for antidepressant medications approved through 2004. We update those findings here for medications approved since 2004. Design: We identified antidepressants approved by the US Food and Dru...

Objectives: This study aimed to determine the presence of spin in papers on positive RCTs of anti-depressant medication for anxiety disorders by comparing concerns expressed in the FDA reviews with concerns expressed in the published paper. Methods: For every positive anxiety medication trial with a matching publication (n=41), two independent re...

Previous research has shown that reporting bias has inflated the apparent efficacy of antidepressants. We investigated whether apparent safety was also affected. We included 133 trials, involving 31,296 patients, of second-generation antidepressants for the treatment of major depressive disorder (MDD) or anxiety disorders, obtained from Food and Dr...

Introduction Many antidepressants are indicated for the treatment of major depression. Two network meta-analyses have provided the most comprehensive assessments to date, accounting for both direct and indirect comparisons; however, these reported conflicting interpretation of results. Here, we present a protocol for a systematic review and network...

Background Antidepressants are established first-line treatments for anxiety disorders, but it is not clear whether they are equally effective across the severity range. Aims To examine the influence of baseline severity of anxiety on antidepressant efficacy for generalised anxiety disorder (GAD), social anxiety disorder (SAD), obsessive-compulsive...

Background: A large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of "positive" results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based t...

Search Strategies. (DOCX)

(DOC)

Characteristics of Mindfulness-Based Therapy Studies in Analysis. (DOCX)

Results from Mindfulness-Based Therapy Studies Included in Analysis. (DOCX)

Characteristics of Mindfulness-Based Therapy Systematic Reviews and Meta-Analyses Included in Analysis. (DOCX)

Characteristics of Mindfulness-Based Therapy Systematic Reviews and Meta-Analyses Included in Analysis. (DOCX)

Characteristics of Mindfulness-Based Therapy Trial Registrations Included in Analysis. (DOCX)

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for de...

Background: Antidepressants are established first-line treatments for anxiety disorders, but it is not clear whether they are equally effective across the severity range. Aims: To examine the influence of baseline severity of anxiety on antidepressant efficacy for generalised anxiety disorder (GAD), social anxiety disorder (SAD), obsessive-compu...

Lurie and colleagues’ comparison of FDA letters not approving applications for new drugs and associated public announcements from sponsors provides a valuable but rare peek behind the Food and Drug Administration’s “iron curtain.” The discussion section begins, “our analysis found that the FDA’s reasons for not approving marketing applications for...

Studies have shown that the scientific literature has overestimated the efficacy of antidepressants for depression, but other indications for these drugs have not been considered. To examine reporting biases in double-blind, placebo-controlled trials on the pharmacologic treatment of anxiety disorders and quantify the extent to which these biases i...

Randomized trials can show whether a treatment effect is statistically significant and can describe the size of the effect. There are, however, no validated methods available for establishing the clinical relevance of these outcomes. Recently, it was proposed that a standardized mean difference (SMD) of 0.50 be used as cutoff for clinical relevance...

Publication bias undermines the integrity of the evidence base by inflating apparent drug efficacy and minimizing drug harms, thus skewing the risk-benefit ratio. This paper reviews the topic of publication bias with a focus on drugs prescribed for psychiatric conditions, especially depression, schizophrenia, bipolar disorder, and autism. Publicati...

Background: The effects of antidepressants for treating depressive disorders have been overestimated because of selective publication of positive trials. Reanalyses that include unpublished trials have yielded reduced effect sizes. This in turn has led to claims that antidepressants have clinically insignificant advantages over placebo and that ps...

FDA databases contain valuable information on unpublished studies, but it can be difficult to find. This article explains where to look and provides tips on how to make documents easier to use Reporting bias leads to an overestimation of drug efficacy and underestimation of drug harms, but its effects can be mitigated by using unpublished data fro...

To investigate the degree to which Cochrane reviews of drug interventions published in 2010 reported conflicts of interest from included trials and, among reviews that reported this information, where it was located in the review documents. Cross sectional study. Cochrane Database of Systematic Reviews. Systematic reviews of drug interventions publ...

Appendices

Meta-analysis of clinical trial data from FDA drug approval packages—output from statistical program Stata. (DOC)

Meta-analysis of clinical trial data from the published literature. Output from statistical program Stata. (DOC)

PRISMA checklist. (DOC)

Supplemental methods and results. (DOC)

Two-by-two tables of trial outcome according to the FDA versus publication status. (DOC)

Linden and Vodermaier1 claim that the rate of false-positives with screening for depression is “very acceptable.” Whether a false-positive rate is acceptable depends on the prevalence of disease in the population being screened. Given the prevalence of depression in a typical primary care setting and that about half of patients with depression are...

Publication bias compromises the validity of evidence-based medicine, yet a growing body of research shows that this problem is widespread. Efficacy data from drug regulatory agencies, e.g., the US Food and Drug Administration (FDA), can serve as a benchmark or control against which data in journal articles can be checked. Thus one may determine wh...

Screening for depression in primary care is an issue that is highly contentious and hotly debated, and recommendations have evolved over time. For example, early policy statements from the 1990s in Canada1 and the United States2 recommended against screening for depression in primary care1 or did not find enough evidence to recommend either for or...

Disclosure of conflicts of interest (COIs) from pharmaceutical industry study funding and author-industry financial relationships is sometimes recommended for randomized controlled trials (RCTs) published in biomedical journals. Authors of meta-analyses, however, are not required to report COIs disclosed in original reports of included RCTs. To inv...

I previously worked at the US Food and Drug Administration (FDA) and was the medical officer who reviewed the new drug application for reboxetine.Eyding and colleagues state, “we are optimistic that we analysed the vast majority or even all” of the relevant data.1 But is such optimism warranted? Because the FDA rejected the reboxetine application f...

A perimenopausal woman with seasonal affective disorder (SAD, winter depression) presented with a 2-year history of hot flashes occurring only in the wintertime. Prospectively documented hot flashes appeared to follow a seasonal rhythm and a bimodal circadian rhythm. The hot flashes decreased with morning, but not evening, light therapy. These obse...

To assess the performance of novel contour enhanced funnel plots and a regression based adjustment method to detect and adjust for publication biases. Secondary analysis of a published systematic literature review. Placebo controlled trials of antidepressants previously submitted to the US Food and Drug Administration (FDA) and matching journal pub...

In their Policy Forum “Moving toward transparency of clinical trials” (7 March, p. [1340][1]), D. A. Zarin and T. Tse caution that “FDAAA 801 still leaves areas of 'opacity.'” We would like to point out another loophole: FDAAA 801 will only cover future drugs. The thousands of drugs on the

Is not an absolute measure, and it depends on how clinical significance is defined

Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials--and the outcomes within those trials--can lead to unrealistic estimates of drug effectiveness and alter the apparent risk-benefit ratio. We obtained reviews from the Food and Drug Administration (FDA) for stud...

This paper reviews the preclinical and clinical evidence regarding the use of the dietary supplement 5-hydroxytryptophan (5-HTP) for the treatment of depression. In the absence of supplementation with exogenous 5-HTP, the amount of endogenous 5-HTP available for serotonin synthesis depends on the availability of tryptophan and on the activity of va...

Background to the debate: Placebos are used in trials to conceal whether a treatment is being given or not and hence to control for the psychosomatic effects of offering treatment. Placebo-controlled trials are controversial. Critics of such trials argue that if a proven effective therapy exists, a placebo should not be used. But proponents argue...

Interferon-alpha (IFN) is widely used in the treatment of certain cancers and viral infections, including hepatitis C (HCV). Unfortunately, depression is a common side effect of IFN therapy, affecting approximately a third of HCV patients receiving IFN therapy. Studies have shown that selective serotonin reuptake inhibitors (SSRIs) can effectively...

It already exists within the US Food and Drug Administration, argues a former clinical reviewer of psychotropic drugs at the FDA.

The authors examined the efficacy of a multifaceted intervention designed to contain the cost of prescribing selective serotonin reuptake inhibitors (SSRIs) to inpatients and outpatients served by a Veterans Affairs (VA) medical center. Elements of the intervention included identification of a preferred agent, tablet splitting, education and feedba...

Behavioral changes in patients with seasonal affective disorder resemble seasonal changes in photoperiodic animals. Because the olfactory system has a modulatory role in seasonal photoperiodic responses in certain species, we hypothesized that olfactory function may differ between patients with seasonal affective disorder and healthy control subjec...

A role for serotonin in season affective disorder (SAD) has been explored with a variety of serotonergic pharmacologic agents. The authors initially hypothesized that metergoline, a nonspecific serotonin antagonist, would exacerbate depressive symptoms. In a small, open-label pilot study, the authors observed the opposite effect. They decided to fo...

In animals, the circadian pacemaker regulates seasonal changes in behavior by transmitting a signal of day length to other sites in the organism. The signal is expressed reciprocally in the duration of nocturnal melatonin secretion, which is longer in winter than in summer. We investigated whether such a signal could mediate the effects of change o...

Objective: To determine if the antidepressant effect of 1 hour of light therapy is predictive of the response after 1 and 2 weeks of treatment in patients with seasonal affective disorder (SAD). Patients: Twelve patients with SAD. Setting: National Institutes of Health Clinical Center, Bethesda, Md. Interventions: Light therapy for 2 weeks....

The level of core body, and presumably brain temperature during sleep varies with clinical state in patients with seasonal affective disorder (SAD), becoming elevated during winter depression and lowered during clinical remission induced by either light treatment or summer. During sleep, brain temperatures are in part determined by the level of bra...

Background: Visual and olfactory pathways are interconnected. Olfactory deafferentation unmasks photoperiodic responsiveness in some nonphotoperiodic animals such as laboratory rats. By analogy, we hypothesized that olfactory deficits may unmask seasonal rhythms in certain individuals, namely those with seasonal affective disorder (SAD). Since pre...

Winter depressions in seasonal affective disorder (SAD) are associated with central serotonergic (5-HT) dysfunction. SAD patients demonstrate rather specific, state-dependent, abnormal increases in 'activation-euphoria' ratings following intravenous infusion of the 5-HT receptor agonist meta-chlorophenylpiperazine (m-CPP). Several studies are also...

Seasonal affective disorder (SAD) has been shown to manifest different symptoms in female and male patients. Specifically, women with SAD have been shown to have greater increases in overeating, weight gain, and increased sleep as compared with their male counterparts. Given these dietary changes, we predicted that female SAD patients would exhibit...

Information-transducing heterotrimeric G proteins have been implicated previously in the mechanism of action of mood stabilizers and in the pathophysiology of mood disorders. Mononuclear leukocytes of patients with unipolar and bipolar depression have been characterized by reduced measures of the stimulatory and inhibitory G proteins. In this study...

The authors sought to compare the degree of mood improvement after light treatment with mood improvement in the subsequent summer in patients with seasonal affective disorder. By using the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale, the authors rated 15 patients with seasonal affective disorder on three occasions: d...

The modern practice of using artificial light to extend waking activities into the nighttime hours might be expected to precipitate or exacerbate bipolar illness, because it has been shown that modifying the timing and duration of sleep can induce mania in susceptible individuals. With this possibility in mind, we treated a patient with rapidly cyc...

Although hypotheses about the therapeutic mechanism of action of light therapy have focused on serotonergic mechanisms, the potential role, if any, of catecholaminergic pathways has not been fully explored. Sixteen patients with seasonal affective disorder who had responded to a standard regimen of daily 10000-lux light therapy were enrolled in a d...

Seasonal variations in mood and behavior (seasonality) and seasonal affective disorder (SAD) have been attributed to seasonal fluctuations in brain serotonin (5-HT). the short (s), as opposed to the long (l), allele of the 5-HT transporter linked polymorphism (5-HTTLPR) has been associated with neuroticism and depression. We hypothesized that this...

We validated the Hypomania Interview Guide-Seasonal Affective Disorder version (HIGH-SAD) in patients with rapid cycling bipolar disorder (RCBD). Fourteen outpatients were rated on six separate occasions (total = 84 visits). On each visit the patients were rated with the HIGH-SAD and the Young Mania Rating Scale (YMRS) in a counterbalanced order. C...

The possible role of gonadal steroids in regulating sleep and circadian rhythms in humans has received relatively little attention despite the importance of the topic to several clinical syndromes. Pharmacologically induced hypogonadism, with and without gonadal steroid replacement, provides an opportunity to examine these questions within a contro...

The ready availability of exogenous melatonin means that its use in patients with mood disorders is probably not uncommon. Nonetheless, few controlled trials of exogenous melatonin in these patients have been conducted. Five patients with rapid-cycling DSM-III-R bipolar disorder were treated with melatonin 10 mg q.d. at 10:00 p.m. for 12 weeks. Mel...