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 logical consistency (LC) checks for ratings of the Young Mania Rating Scale (YMRS), which is widely used in studies of mood and bipolar disorders. LC and statistical outlier-response pattern checks (SC) were applied to 63,228 YMRS administrations from 14 clinical trials evaluating treatments for bipolar disorder. Checks were also applied to Monte Carlo-simulated data as a proxy for their use under conditions of inconsistency. RESULTS: 42 LC flags were developed, and four SC flags were created from the data set (n = 14). Almost 20 % of the rating administrations had at least one LC flag, 6.7 % had two or more, 1.7 % had three or more; 17.3 % percent of the administrations had at least one SC flag and 4.6 % percent had two or more. Overall, 31 % of administrations had at least one flag of any type, 12.1 % had two or more and 5.3 % had three or more. In acute antimanic treatment trials (n = 10) there were more flags of any type compared to relapse prevention trials (n = 4). LIMITATIONS: Flagged ratings may represent less-common presentations assessed correctly. CONCLUSIONS: Using established methods, we illustrate development and application of consistency flags for YMRS ratings. Applying flags and mitigation during trials may improve the value of YMRS data, help focus attention on rater training, and improve reliability and validity of trial data.
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.
- MeSH
- lidé MeSH
- psychiatrické posuzovací škály MeSH
- psychometrie MeSH
- reprodukovatelnost výsledků MeSH
- úzkost * MeSH
- úzkostné poruchy * diagnóza farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
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.
International Society for CNS Clinical Trials and Methodology convened an expert Working Group that assembled consistency/inconsistency flags for the Personal and Social Performance Scale (PSP). One hundred and forty seven flags were identified, 16 flag errors in deriving the PSP decile (i.e., total) score from the four individual domain scores, 74 flag inconsistencies between domain scores relative to Positive and Negative Symptom Scale (PANSS) item ratings and 57 flag inconsistencies between PSP decile score and PANSS items ratings. The flags were applied to assessments from randomized clinical trial data of antipsychotics in schizophrenia from almost 18,000 ratings. Twenty-two flags were raised in at least 5 of 1000 ratings. Nearly 20% of the PSP ratings had at least one inconsistency flag raised. Application of flags to clinical ratings may improve the reliability of ratings and validity of trials.
Objective: In the current posthoc analyses, we evaluated the impact of markers of aberrant data variability on drug placebo separation and placebo and drug response in an acute schizophrenia clinical trial. Methods: Positive and negative syndrome scale data were obtained from a phase 2, randomized, double-blind, placebo controlled trial in hospitalized adults with schizophrenia experiencing an acute exacerbation. We assessed the impact of a total of six markers of aberrant data variability: erratic ratings, unusually large postbaseline improvement, high and low mean square successive difference (MSSD), identical and nearly identical ratings and compared the drug placebo difference, drug and treatment response at last visit in affected subjects vs those not affected. All analyses were conducted using generalized linear models. Results: In this posthoc analysis, drug placebo separation decreased with the presence of most markers of aberrant data variability. The only exception was high MSSD was associated with significant increase in the signal. In the affected subjects, the presence of indicators of increased data variability augmented the response to placebo, in the case of large postbaseline change and high MSSD, significantly. The presence of indicators of decreased variability numerically but not statistically decreased the response to placebo. Similar findings were observed in the drug treatment group with the exception of erratic ratings that numerically but not statistically decreased the response to the drug. Discussion: The presence of most indicators of aberrant data variability had a detrimental effect on drug-placebo separation and showed different effects on placebo and treatment response.
- Publikační typ
- časopisecké články MeSH
Background: Patients with schizophrenia who, prior to inclusion in placebo-controlled trials, experience the most severe and/or unstable symptoms might be more likely to manifest symptomatic worsening upon antipsychotic discontinuation. Methods: This retrospective analysis included all randomized patients assigned to placebo (n=83) in a 12-week, double-blind, placebo-controlled outpatient trial of MIN-101 (roluperidone) for the treatment of negative symptoms in schizophrenia. The following risk factors were defined for exacerbation: instability between screening and baseline defined operationally as patients with the highest 10 percent of absolute change from the screening visit to baseline in the Positive and Negative Syndrome Scale (PANSS) total or one of the five PANSS Marder factors; screening or baseline severity in PANSS total or one of the five PANSS Marder factors; and gender and age. We used two operational criteria of relapse and the odds ratios of meeting the relapse criteria were calculated for each risk factor. Results: The odds of meeting one of the operational thresholds for relapse after antipsychotic discontinuation were not statistically significantly increased in the subjects who were unstable on the PANSS total or on one of the five PANSS Marder factors before antipsychotic discontinuation. Further, the severity of PANSS total and Marder factor scores at screening and baseline were not statistically significantly associated with odds of relapse. Neither age nor gender had any effect on relapse rates. Conclusion: Mild to moderate symptomatic variations in the severity of symptoms during screening and more severe symptomology at baseline as measured by the PANSS were not predictive of increased risk of subsequent relapse in schizophrenic patients.
- Publikační typ
- časopisecké články MeSH
Sertralin je antidepresivum ze skupiny inhibitoru zpětného vychytávání serotoninu (SSRI). Mechanismus vlastní inhibice zpětného vychytávání spočívá v inhibici funkce presynaptických serotoninových transportéru. Po perorálním podání se sertralin vstřebává pomalu, ale rovnoměrně, rovnovážných plazmatických koncentrací je u dospělých dosaženo do 7 dnu, u starších pacientu se tato doba prodlužuje na 2–3 týdny. Sertralin je účinný v léčbě deprese i deprese provázené úzkostí, posttraumatické stresové poruchy, obsedantně-kompulzivních poruch a panické poruchy spojené s agorafobií nebo bez přítomnosti agorafobie. Sertralin patří mezi dobře snášená antidepresiva s minimálním množstvím nežádoucích účinku, které jsou většinou mírného charakteru. Obvyklá dávka sertralinu při léčbě deprese je 50 mg 1x denně.
Sertraline is an antidepressant belonging to a group of medicines known as selective serotonin reuptake inhibitors (SSRI). The mechanism of serotonin reuptake inhibition is based on inhibition of function of presynaptic serotonin transporters. Sertraline is slowly but evenly absorbed following oral administration, steady state plasma concentrations are achieved within 7 days in adults and within 2 to 3 weeks in elderly patients. Sertraline is effective in the treatment of depression and depression with associated anxiety symptoms, posttraumatic stress disorder, obsessive-compulsive disorders and panic disorder associated with agoraphobia or without agoraphobia. Sertraline is a well tolerated antidepressant, low in side effects, which are mostly mild. The usual dosage of Sertraline for the treatment of depression is 50 mg once daily.
