Comparison of Site-Based Versus Central Ratings in a Study of Generalized Anxiety Disorder.

Lack of standardization across sites and raters, poor interrater reliability, and possible scoring bias affecting the primary outcome measure contribute to a high failure rate in anxiety trials. Remote centralized raters who are blinded to protocol inclusion and exclusion criteria as well as visit number may standardize assessments across raters and eliminate scoring bias, decreasing placebo response and thereby increasing signal detection. The purpose of the primary study was to test the safety and efficacy of an anxiolytic in a double-blind, placebo-controlled (no active comparator), multicenter trial. However, there was an additional prospective objective to explore site ratings compared with remote centralized ratings in the cohort of subjects on placebo. Site raters assessed subjects 6 times over an 8-week period. The primary outcome measure was the week 8 site-rated Hamilton Anxiety Scale (HAM-A). Remote centralized raters by telephone independently rated these subjects on the HAM-A at baseline and week 6. Of the 122 subjects selected by site raters and therefore randomized, remote centralized raters would have admitted 59 (48%) and excluded 63 (52%), based on their HAM-A ratings. The mean change from baseline in HAM-A total score in the placebo group admitted to the study by site raters was 9.3, significantly higher than the 5.9 point mean change on placebo as measured by the remote centralized raters.The data are consistent with the potential for qualification bias at baseline when rated by sites. The results make a strong case for using strategies to ensure that baseline scoring is truly independent of the pressure to enroll.

Consistency checks to improve measurement with the Hamilton Rating Scale for Anxiety (HAM-A).

BACKGROUND: Mitigating rating inconsistency can improve measurement fidelity and detection of treatment response. METHODS: The International Society for CNS Clinical Trials and Methodology convened an expert Working Group that developed consistency checks for ratings of the Hamilton Anxiety Rating Scale (HAM-A) and Clinical Global Impression of Severity of anxiety (CGIS) that are widely used in studies of mood and anxiety disorders. Flags were applied to 40,349 HAM-A administrations from 15 clinical trials and to Monte Carlo-simulated data as a proxy for applying flags under conditions of inconsistency. RESULTS: Thirty-three flags were derived these included logical consistency checks and statistical outlier-response pattern checks. Twenty-percent of the HAM-A administrations had at least one logical scoring inconsistency flag, 4 % had two or more. Twenty-six percent of the administrations had at least one statistical outlier flag and 11 % had two or more. Overall, 35 % of administrations had at least one flag of any type, 19 % had one and 16 % had 2 or more. Most of administrations in the Monte Carlo- simulated data raised multiple flags. LIMITATIONS: Flagged ratings may represent less-common presentations of administrations done correctly. Conclusions-Application of flags to clinical ratings may aid in detecting imprecise measurement. Flags can be used for monitoring of raters during an ongoing trial and as part of post-trial evaluation. Appling flags may improve reliability and validity of trial data.

SIGH, what's in a name? An examination of the factor structure and criterion validity of the (Structured Interview Guide for the) Hamilton Anxiety scale (SIGH-A) in a sample of African American adults with co-occurring trauma experience and heavy alcohol use.

The Hamilton Anxiety Inventory (HAM-A) is one of the oldest and most commonly used anxiety rating scales in clinical research. Despite its ubiquity, no studies have examined the scale's underlying factor structure and criterion validity among Black and African American adults with psychopathology (Mage = 42.25, SD = 11.44). Therefore, we estimated a confirmatory factor analysis of the commercially available Structured Interview Guide for the Hamilton Anxiety scale (SIGH-A; Williams, 1996) among African American adults (n = 88; 43% female) with co-occurring heavy alcohol use and trauma-related symptoms. Next, we examined the criterion validity of its Psychic and Somatic factors and overall anxiety severity score from participants who completed a single screening session (i.e., cross-sectional analysis) for a larger study. Results indicated that a two-factor solution provided an adequate fit to the data. Regression analyses indicated that the total SIGH-A score, but not its subscales, significantly predicted posttraumatic stress disorder (PTSD) severity. Neither the SIGH-A subscales nor total scores were significant predictors of alcohol consumption. The current findings suggest that the SIGH-A factor structure among African American adults with alcohol and trauma-related conditions is similar to previous reports that have tested largely White samples but highlight potential shortcomings when its subscales are used independently. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Consistency checks to improve measurement with the Hamilton Rating Scale for Depression (HAM-D).

BACKGROUND: Symptom manifestations in mood disorders can be subtle. Cumulatively, small imprecisions in measurement can limit our ability to measure treatment response accurately. Logical and statistical consistency checks between item responses (i.e., cross-sectionally) and across administrations (i.e., longitudinally) can contribute to improving measurement fidelity. METHODS: The International Society for CNS Clinical Trials and Methodology convened an expert Working Group that assembled flags indicating consistency/inconsistency ratings for the Hamilton Rating Scale for Depression (HAM-D17), a widely-used rating scale in studies of depression. Proposed flags were applied to assessments derived from the NEWMEDS data repository of 95,468 HAM-D administrations from 32 registration trials of antidepressant medications and to Monte Carlo-simulated data as a proxy for applying flags under conditions of known inconsistency. RESULTS: Two types of flags were derived: logical consistency checks and statistical outlier-response pattern checks. Almost thirty percent of the HAMD administrations had at least one logical scoring inconsistency flag. Seven percent had flags judged to suggest that a thorough review of rating is warranted. Almost 22% of the administrations had at least one statistical outlier flag and 7.9% had more than one. Most of the administrations in the Monte Carlo- simulated data raised multiple flags. LIMITATIONS: Flagged ratings may represent less-common presentations of administrations done correctly. CONCLUSIONS: Application of flags to clinical ratings may aid in detecting imprecise measurement. Reviewing and addressing these flags may improve reliability and validity of clinical trial data.

Attitudes toward borderline personality disorder: a survey of 706 mental health clinicians.

OBJECTIVE: We sought to determine attitudes toward patients with borderline personality disorder (BPD) among mental health clinicians at nine academic centers in the United States. METHODS: A self-report questionnaire was distributed to 706 mental health clinicians, including psychiatrists, psychiatry residents, social workers, nurses, and psychologists. RESULTS: The study showed that most clinicians consider BPD a valid diagnosis, although nearly half reported that they preferred to avoid these patients. The clinician's occupational subgroup was significantly related to attitude. Staff nurses had the lowest self-ratings on overall caring attitudes, while social workers had the highest. Social workers and psychiatrists had the highest ratings on treatment optimism. Social workers and psychologists were most optimistic about psychotherapy effectiveness, while psychiatrists were most optimistic about medication effectiveness. Staff nurses had the lowest self-ratings on empathy toward patients with BPD and treatment optimism.DiscussionNegative attitudes persist among clinicians toward BPD, but differ among occupational subgroups. Overall, caring attitudes, empathy, and treatment optimism were all higher among care providers who had cared for a greater number of BPD patients in the past 12 months. CONCLUSION: These findings hold important implications for clinician education and coordination of care for patients with BPD.

Site versus centralized raters in a clinical depression trial: impact on patient selection and placebo response.

The use of centralized raters who are remotely linked to sites and interview patients via videoconferencing or teleconferencing has been suggested as a way to improve interrater reliability and interview quality. This study compared the effect of site-based and centralized ratings on patient selection and placebo response in subjects with major depressive disorder. Subjects in a 2-center placebo and active comparator controlled depression trial were interviewed twice at each of 3 time points: baseline, 1-week postbaseline, and end point--once by the site rater and once remotely via videoconference by a centralized rater. Raters were blind to each others' scores. A site-based score of greater than 17 on the 17-item Hamilton Depression Rating Scale (HDRS-17) was required for study entry. When examining all subjects entering the study, site-based raters' HDRS-17 scores were significantly higher than centralized raters' at baseline and postbaseline but not at end point. At baseline, 35% of subjects given an HDRS-17 total score of greater than 17 by a site rater were given an HDRS total score of lower than 17 by a centralized rater and would have been ineligible to enter the study if the centralized rater's score was used to determine study entry. The mean placebo change for site raters (7.52) was significantly greater than the mean placebo change for centralized raters (3.18, P < 0.001). Twenty-eight percent were placebo responders (>50% reduction in HDRS) based on site ratings versus 14% for central ratings (P < 0.001). When examining data only from those subjects whom site and centralized raters agreed were eligible for the study, there was no significant difference in the HDRS-17 scores. Findings suggest that the use of centralized raters could significantly change the study sample in a major depressive disorder trial and lead to significantly less change in mood ratings among those randomized to placebo.

THE DEPRESSION INVENTORY DEVELOPMENT SCALE: Assessment of Psychometric Properties Using Classical and Modern Measurement Theory in a CAN-BIND Trial.

Objective: The goal of the Depression Inventory Development (DID) project is to develop a comprehensive and psychometrically sound rating scale for major depressive disorder (MDD) that reflects current diagnostic criteria and conceptualizations of depression. We report here the evaluation of the current DID item bank using Classical Test Theory (CTT), Item Response Theory (IRT) and Rasch Measurement Theory (RMT). Methods: The present study was part of a larger multisite, open-label study conducted by the Canadian Biomarker Integration Network in Depression (ClinicalTrials.gov: NCT01655706). Trained raters administered the 32 DID items at each of two visits (MDD: baseline, n=211 and Week 8, n=177; healthy participants: baseline, n=112 and Week 8, n=104). The DID's "grid" structure operationalizes intensity and frequency of each item, with clear symptom definitions and a structured interview guide, with the current iteration assessing symptoms related to anhedonia, cognition, fatigue, general malaise, motivation, anxiety, negative thinking, pain, and appetite. Participants were also administered the Montgomery- Åsberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) that allowed DID items to be evaluated against existing "benchmark" items. CTT was used to assess data quality/reliability (i.e., missing data, skewness, scoring frequency, internal consistency), IRT to assess individual item performance by modelling an item's ability to discriminate levels of depressive severity (as assessed by the MADRS), and RMT to assess how the items perform together as a scale to capture a range of depressive severity (item targeting). These analyses together provided empirical evidence to base decisions on which DID items to remove, modify, or advance. Results: Of the 32 DID items evaluated, eight items were identified by CTT as problematic, displaying low variability in the range of responses, floor effects, and/or skewness; and four items were identified by IRT to show poor discriminative properties that would limit their clinical utility. Five additional items were deemed to be redundant. The remaining 15 DID items all fit the Rasch model, with person and item difficulty estimates indicating satisfactory item targeting, with lower precision in participants with mild levels of depression. These 15 DID items also showed good internal consistency (alpha=0.95 and inter-item correlations ranging from r=0.49 to r=0.84) and all items were sensitive to change following antidepressant treatment (baseline vs. Week 8). RMT revealed problematic item targeting for the MADRS and QIDSSR, including an absence of MADRS items targeting participants with mild/moderate depression and an absence of QIDS-SR items targeting participants with mild or severe depression. Conclusion: The present study applied CTT, IRT, and RMT to assess the measurement properties of the DID items and identify those that should be advanced, modified, or removed. Of the 32 items evaluated, 15 items showed good measurement properties. These items (along with previously evaluated items) will provide the basis for validation of a penultimate DID scale assessing anhedonia, cognitive slowing, concentration, executive function, recent memory, drive, emotional fatigue, guilt, self-esteem, hopelessness, tension, rumination, irritability, reduced appetite, insomnia, sadness, worry, suicidality, and depressed mood. The strategies adopted by the DID process provide a framework for rating scale development and validation.

Sources of unreliability in depression ratings.

BACKGROUND: Good interrater reliability is essential to minimize error variance and improve study power. Reasons why raters differ in scoring the same patient include information variance (different information obtained because of asking different questions), observation variance (the same information is obtained, but raters differ in what they notice and remember), interpretation variance (differences in the significance attached to what is observed), criterion variance (different criteria used to score items), and subject variance (true differences in the subject). We videotaped and transcribed 30 pairs of interviews to examine the most common sources of rater unreliability. METHOD: Thirty patients who experienced depression were independently interviewed by 2 different raters on the same day. Raters provided rationales for their scoring, and independent assessors reviewed the rationales, the interview transcripts, and the videotapes to code the main reason for each discrepancy. One third of the interviews were conducted by raters who had not administered the Hamilton Depression Rating Scale before; one third, by raters who were experienced but not calibrated; and one third, by experienced and calibrated raters. RESULTS: Experienced and calibrated raters had the highest interrater reliability (intraclass correlation [ICC]; r = 0.93) followed by inexperienced raters (r = 0.77) and experienced but uncalibrated raters (r = 0.55). The most common reason for disagreement was interpretation variance (39%), followed by information variance (30%), criterion variance (27%), and observation variance (4%). Experienced and calibrated raters had significantly less criterion variance than the other cohorts (P = 0.001). CONCLUSIONS: Reasons for disagreement varied by level of experience and calibration. Experienced and uncalibrated raters should focus on establishing common conventions, whereas experienced and calibrated raters should focus on fine tuning judgment calls on different thresholds of symptoms. Calibration training seems to improve reliability over experience alone. Experienced raters without cohort calibration had lower reliability than inexperienced raters.

An ultra-brief screening scale for anxiety and depression: the PHQ-4.

BACKGROUND: The most common mental disorders in both outpatient settings and the general population are depression and anxiety, which frequently coexist. Both of these disorders are associated with considerable disability. OBJECTIVE: When the disorders co-occur, the disability is even greater. Authors sought to test an ultra-brief screening tool for both. METHOD: Validated two-item ultra-brief screeners for depression and anxiety were combined to constitute the Patient Health Questionnaire for Depression and Anxiety (the PHQ-4). Data were analyzed from 2,149 patients drawn from 15 primary-care clinics in the United States. RESULTS: Factor analysis confirmed two discrete factors (Depression and Anxiety) that explained 84% of the total variance. Increasing PHQ-4 scores were strongly associated with functional impairment, disability days, and healthcare use. Anxiety had a substantial effect on functional status that was independent of depression. CONCLUSION: The PHQ-4 is a valid ultra-brief tool for detecting both anxiety and depressive disorders.

Consistency checks to improve measurement with the Montgomery-Asberg Depression Rating Scale (MADRS).

International Society for CNS Clinical Trials and Methodology convened an expert Working Group that assembled consistency/inconsistency flags for the Montgomery-Asberg Depression Rating Scale (MADRS). Twenty-two flags were identified. Seven flags are believed to be strong flags that suggest that a thorough review of rating is warranted. The flags were applied to assessments derived from the NEWMEDS data repository. Almost 65% of ratings had at least one inconsistency flag raised and 22% had two or more. Application of flags to clinical ratings may improve reliability of ratings and validity of trials.

Face-to-face versus remote administration of the Montgomery-Asberg Depression Rating Scale using videoconference and telephone.

Although the use of telemedicine in psychiatry has a long history in providing clinical care to patients, its use in clinical trials research has not yet been commonly employed. Telemedicine allows for the remote assessment of study patients, which could be done by a centralized, highly calibrated, and impartial cohort of raters independent of the study site. This study examined the comparability of remote administration of the Montgomery-Asberg Depression Rating Scale (MADRS) by videoconference and by telephone to traditional face-to-face administration. Two parallel studies were conducted: one compared face-to-face with videoconference administration (N=35), and the other compared face-to-face with telephone administration (N=35). In each study, depressed patients were interviewed independently twice: once in the traditional face-to-face manner, and the second time by either videoconference or teleconference. A counterbalanced order was used. The mean MADRS score for interviews conducted remotely by videoconference was not significantly different from the mean MADRS scores conducted by face-to-face administration (mean difference=0.51 points), P=.388, intraclass correlation (ICC)=.94, P<0001. Similarly, the mean MADRS score for interviews conducted by telephone was not significantly different from the mean MADRS score conducted by face-to-face administration (mean difference=0.74 points), P=.270, ICC=.93, P<0001. Results of the study support the comparability of remote administration of the MADRS, by both telephone and videoconference, to face-to-face administration. Comparability of the administration mode allows for remote assessment of patients in both research and clinical applications.

Depression, anxiety and somatization in primary care: syndrome overlap and functional impairment.

OBJECTIVE: To determine diagnostic overlap of depression, anxiety and somatization as well as their unique and overlapping contribution to functional impairment. METHOD: Two thousand ninety-one consecutive primary care clinic patients participated in a multicenter cross-sectional survey in 15 primary care clinics in the United States (participation rate, 92%). Depression, anxiety, somatization and functional impairment were assessed using validated scales from the Patient Health Questionnaire (PHQ) (PHQ-8, eight-item depression module; GAD-7, seven-item Generalized Anxiety Disorder Scale; and PHQ-15, 15-item somatic symptom scale) and the Short-Form General Health Survey (SF-20). Multiple linear regression analyses were used to investigate unique and overlapping associations of depression, anxiety and somatization with functional impairment. RESULTS: In over 50% of cases, comorbidities existed between depression, anxiety and somatization. The contribution of the commonalities of depression, anxiety and somatization to functional impairment substantially exceeded the contribution of their independent parts. Nevertheless, depression, anxiety and somatization did have important and individual effects (i.e., separate from their overlap effect) on certain areas of functional impairment. CONCLUSIONS: Given the large syndrome overlap, a potential consideration for future diagnostic classification would be to describe basic diagnostic criteria for a single overarching disorder and to optionally code additional diagnostic features that allow a more detailed classification into specific depressive, anxiety and somatoform subtypes.

The GRID-HAMD: standardization of the Hamilton Depression Rating Scale.

This report describes the GRID-Hamilton Depression Rating Scale (GRID-HAMD), an improved version of the Hamilton Depression Rating Scale that was developed through a broad-based international consensus process. The GRID-HAMD separates the frequency of the symptom from its intensity for most items, refines several problematic anchors, and integrates both a structured interview guide and consensus-derived conventions for all items. Usability was established in a small three-site sample of convenience, evaluating 29 outpatients, with most evaluators finding the scale easy to use. Test-retest (4-week) and interrater reliability were established in 34 adult outpatients with major depressive disorder, as part of an ongoing clinical trial. In a separate study, interrater reliability was found to be superior to the Guy version of the HAMD, and as good as the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D), across 30 interview pairs. Finally, using the SIGH-D as the criterion standard, the GRID-HAMD demonstrated high concurrent validity. Overall, these data suggest that the GRID-HAMD is an improvement over the original Guy version as well as the SIGH-D in its incorporation of innovative features and preservation of high reliability and validity.

Gastrointestinal symptoms in primary care: prevalence and association with depression and anxiety.

OBJECTIVE: Results from general population studies suggest a relationship between gastrointestinal (GI) symptoms, depression, and anxiety. However, no primary care study has investigated this issue. This study investigates the prevalence of GI symptoms in primary care and their association with depression and anxiety. METHOD: Within a cross-sectional survey, 2091 consecutive patients from 15 primary care clinics in the United States completed self-report questionnaires regarding GI symptoms [15-item Patient Health Questionnaire (PHQ-15)], anxiety [seven-item Generalized Anxiety Disorder Scale (GAD-7)], and depression (PHQ-8). Of those, 965 randomly selected patients additionally underwent a criterion standard diagnostic telephone interview (Structured Clinical Interview for DSM-IV) for the most common anxiety disorders. RESULTS: A total of 380 [18% (95% CI, 16.3% to 19.3%)] patients reported to be substantially bothered by at least one GI symptom in the previous 4 weeks. The prevalence of severe levels of depression (PHQ-8 score > or =15) was nearly fivefold in patients with GI symptoms compared to patients without GI symptoms (19.1% vs. 3.9%; P<.001), and the prevalence of severe levels of anxiety (GAD-7 score > or =15) was nearly fourfold in patients with GI symptoms compared to patients without GI symptoms (19.4% vs. 5.6%; P<.001). Similarly, with each additional GI symptom, the odds for an interview-based diagnosis of specific anxiety disorders increased significantly: For example, compared to patients with no GI symptom, the odds ratio (OR) (95% CI) for generalized anxiety disorder in patients with one GI symptom was 3.7 (2.0 to 6.9); in patients with two GI symptoms, OR=6.5 (3.1 to 13.6); and in patients with three GI symptoms, OR=7.2 (2.7 to 18.8). CONCLUSION: GI symptoms are associated significantly with depression and anxiety in primary care. It is suggested to screen as a routine for anxiety and depression in patients with GI symptoms and, if indicated, to initiate specific treatment.

A comparison of face-to-face and remote assessment of inter-rater reliability on the Hamilton Depression Rating Scale via videoconferencing.

Poor inter-rater reliability (IRR) is an important methodological factor that may contribute to failed trials. The sheer number of raters at diverse sites in multicenter trials presents a formidable challenge in calibration. Videoconferencing allows for the evaluation of IRR of raters at diverse sites by enabling raters at different sites to each independently interview a common patient. This is a more rigorous test of IRR than passive rating of videotapes. To evaluate the potential impact of videoconferencing on IRR, we compared IRR obtained via videoconference to IRR obtained using face-to-face interviews. Four raters at three different locations were paired using all pair-wise combinations of raters. Using videoconferencing, each paired rater independently conducted an interview with the same patient, who was at a third, central location. Raters were blind to each others' scores. ICC from this cohort (n=22) was not significantly different from the ICC obtained by a cohort using two face-to-face interviews (n=21) (0.90 vs. 0.93, respectively) nor from a cohort using one face-to-face interview and one remote interview (n=21) (0.88). The mean Hamilton Depression Rating Scale (HAMD) scores obtained were not significantly different. There appears to be no loss of signal using remote methods of calibration compared with traditional face-to-face methods.

Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection.

BACKGROUND: Anxiety, although as common as depression, has received less attention and is often undetected and undertreated. OBJECTIVE: To determine the current prevalence, impairment, and comorbidity of anxiety disorders in primary care and to evaluate a brief measure for detecting these disorders. DESIGN: Criterion-standard study performed between November 2004 and June 2005. SETTING: 15 U.S. primary care clinics. PARTICIPANTS: 965 randomly sampled patients from consecutive clinic patients who completed a self-report questionnaire and agreed to a follow-up telephone interview. MEASUREMENTS: 7-item anxiety measure (Generalized Anxiety Disorder [GAD]-7 scale) in the clinic, followed by a telephone-administered, structured psychiatric interview by a mental health professional who was blinded to the GAD-7 results. Functional status (Medical Outcomes Study Short Form-20), depressive and somatic symptoms, and self-reported disability days and physician visits were also assessed. RESULTS: Of the 965 patients, 19.5% (95% CI, 17.0% to 22.1%) had at least 1 anxiety disorder, 8.6% (CI, 6.9% to 10.6%) had posttraumatic stress disorder, 7.6% (CI, 5.9% to 9.4%) had a generalized anxiety disorder, 6.8% (CI, 5.3% to 8.6%) had a panic disorder, and 6.2% (CI, 4.7% to 7.9%) had a social anxiety disorder. Each disorder was associated with substantial impairment that increased significantly (P < 0.001) as the number of anxiety disorders increased. Many patients (41%) with an anxiety disorder reported no current treatment. Receiver-operating characteristic curve analysis showed that both the GAD-7 scale and its 2 core items (GAD-2) performed well (area under the curve, 0.80 to 0.91) as screening tools for all 4 anxiety disorders. LIMITATION: The study included a nonrandom sample of selected primary care practices. CONCLUSIONS: Anxiety disorders are prevalent, disabling, and often untreated in primary care. A 2-item screening test may enhance detection.

A novel approach to rater training and certification in multinational trials.

Clinical trials are becoming increasingly international in scope. Global studies pose unique challenges in training and calibrating raters owing to language and cultural differences. Recent findings that poorly conducted interviews reduce study power, makes attention to raters' clinical skills critical. In this study, 109 raters from 14 countries went through a two-step certification process on the Hamilton Depression and Anxiety Rating Scales: (i) an online didactic tutorial on scoring conventions, and (ii) applied clinical training, consisting of small language-specific groups in which raters took turns interviewing patients while observed by an expert trainer, and observation and evaluation of individual interviews. Translators were used when native-language trainers were unavailable. Those who were unable to attend the startup meeting received the training individually via telephone. Results found a significant improvement in raters' knowledge of scoring conventions, with the mean number of correct answers on the 20-item test improving from 14.59 to 17.83, P<0.0001. In addition, raters' clinical skills improved significantly, with the mean score on the Rater Applied Performance Scale improving from their first to their second testing from 10.25 to 11.31, P=0.003. These results support the efficacy of this applied training model in improving raters' applied clinical skills in multinational trials.

A brief measure for assessing generalized anxiety disorder: the GAD-7.

BACKGROUND: Generalized anxiety disorder (GAD) is one of the most common mental disorders; however, there is no brief clinical measure for assessing GAD. The objective of this study was to develop a brief self-report scale to identify probable cases of GAD and evaluate its reliability and validity. METHODS: A criterion-standard study was performed in 15 primary care clinics in the United States from November 2004 through June 2005. Of a total of 2740 adult patients completing a study questionnaire, 965 patients had a telephone interview with a mental health professional within 1 week. For criterion and construct validity, GAD self-report scale diagnoses were compared with independent diagnoses made by mental health professionals; functional status measures; disability days; and health care use. RESULTS: A 7-item anxiety scale (GAD-7) had good reliability, as well as criterion, construct, factorial, and procedural validity. A cut point was identified that optimized sensitivity (89%) and specificity (82%). Increasing scores on the scale were strongly associated with multiple domains of functional impairment (all 6 Medical Outcomes Study Short-Form General Health Survey scales and disability days). Although GAD and depression symptoms frequently co-occurred, factor analysis confirmed them as distinct dimensions. Moreover, GAD and depression symptoms had differing but independent effects on functional impairment and disability. There was good agreement between self-report and interviewer-administered versions of the scale. CONCLUSION: The GAD-7 is a valid and efficient tool for screening for GAD and assessing its severity in clinical practice and research.

Primary care patients in psychiatric clinical trials: a pilot study using videoconferencing.

BACKGROUND: While primary care physicians play a pivotal role in the treatment of depression, collaboration between primary care and psychiatry in clinical research has been limited. Primary care settings provide unique opportunities to improve the methodology of psychiatric clinical trials, by providing more generalizable and less treatment-resistant patients. We examined the feasibility of identifying, recruiting, screening and assessing primary care patients for psychiatric clinical trials using high-quality videoconferencing in a mock clinical trial. METHODS: 1329 patients at two primary care clinics completed a self-report questionnaire. Those screening positive for major depression, panic, or generalized anxiety were given a diagnostic interview via videoconference. Those eligible were provided treatment as usual by their primary care physician, and had 6 weekly assessments by the off-site clinician via videoconferencing. RESULTS: 45 patients were enrolled over 22 weeks, with 36 (80%) completing the six-week study with no more than two missed appointments. All diagnostic groups improved significantly; 94% reported they would participate again, 87% would recommend participation to others, 96% felt comfortable communicating via videoconference, and 94% were able to satisfactorily communicate their feelings via video. CONCLUSION: Results showed that primary care patients will enroll, participate in and complete psychiatric research protocols using remote interviews conducted via videoconference.

The Depression Inventory Development Workgroup: A Collaborative, Empirically Driven Initiative to Develop a New Assessment Tool for Major Depressive Disorder.

The Depression Inventory Development project is an initiative of the International Society for CNS Drug Development whose goal is to develop a comprehensive and psychometrically sound measurement tool to be utilized as a primary endpoint in clinical trials for major depressive disorder. Using an iterative process between field testing and psychometric analysis and drawing upon expertise of international researchers in depression, the Depression Inventory Development team has established an empirically driven and collaborative protocol for the creation of items to assess symptoms in major depressive disorder. Depression-relevant symptom clusters were identified based on expert clinical and patient input. In addition, as an aid for symptom identification and item construction, the psychometric properties of existing clinical scales (assessing depression and related indications) were evaluated using blinded datasets from pharmaceutical antidepressant drug trials. A series of field tests in patients with major depressive disorder provided the team with data to inform the iterative process of scale development. We report here an overview of the Depression Inventory Development initiative, including results of the third iteration of items assessing symptoms related to anhedonia, cognition, fatigue, general malaise, motivation, anxiety, negative thinking, pain and appetite. The strategies adopted from the Depression Inventory Development program, as an empirically driven and collaborative process for scale development, have provided the foundation to develop and validate measurement tools in other therapeutic areas as well.