Expressing the magnitude of adverse effects in case-control studies: "the number of patients needed to be treated for one additional patient to be harmed".
Ontology highlight
ABSTRACT:
SUBMITTER: Bjerre LM
PROVIDER: S-EPMC1127536 | biostudies-literature | 2000 Feb
REPOSITORIES: biostudies-literature
Publications
Expressing the magnitude of adverse effects in case-control studies: "the number of patients needed to be treated for one additional patient to be harmed".
BMJ (Clinical research ed.) 20000201 7233
Similar Datasets
Project description:IntroductionThe objective was to use the evidence-based medicine metrics of number needed to treat, number needed to harm, and likelihood to be helped or harmed to appraise the clinical efficacy and tolerability of sublingual dexmedetomidine in adults with agitation associated with schizophrenia or bipolar disorder.MethodsSublingual dexmedetomidine data for this post hoc analysis were obtained from two similarly designed, double-blind, randomized, placebo-controlled studies of adults with schizophrenia or bipolar disorder. Response to treatment was defined as a ≥ 40% reduction from baseline in the Positive and Negative Syndrome Scale-Excited Component (PEC). Tolerability was assessed by evaluating rates of adverse events.ResultsThe number needed to treat (95% confidence interval) estimate versus placebo for PEC response at 2 h post-dose was 3 (2, 3) for the sublingual dexmedetomidine 180-µg group (n = 125) and 3 (3, 4) for the 120-µg group (n = 129) in the study of patients with schizophrenia and 3 (2, 3) for the sublingual dexmedetomidine 180-µg group (n = 126) and 4 (3, 6) for the 120-µg group (n = 126) in the study of patients with bipolar disorder. Number needed to harm values versus placebo were greater than 10 for all adverse events except somnolence, where the number needed to harm (95% confidence interval) was 7 (5, 10) for all doses pooled from both studies. In all instances, likelihood to be helped or harmed values were greater than 1 for efficacy versus applicable tolerability outcomes.ConclusionsThe number needed to treat, number needed to harm, and likelihood to be helped or harmed of sublingual dexmedetomidine support a favorable benefit-risk profile in adults with acute agitation associated with schizophrenia or bipolar disorder.Trial registrationClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT04268303 , NCT04268303.Clinicaltrialsgov, https://clinicaltrials.gov/ct2/show/NCT04276883 , NCT04276883.
| S-EPMC9464744 | biostudies-literature
Project description: Not available
| S-EPMC6760268 | biostudies-literature
Project description:BackgroundWe propose a new measure of treatment effect based on the expected reduction in the number of patients to treat (RNT) which is defined as the difference of the reciprocals of clinical measures of interest between two arms. Compared with the conventional number needed to treat (NNT), RNT shows superiority with both binary and time-to-event endpoints in randomized controlled trials (RCTs).MethodsFive real RCTs, two with binary endpoints and three with survival endpoints, are used to illustrate the concept of RNT and compare the performances between RNT and NNT. For survival endpoints, we propose two versions of RNT: one is based on the survival rate and the other is based on the restricted mean survival time (RMST). Hypothetical scenarios are also constructed to explore the advantages and disadvantages of RNT and NNT.ResultsBecause there is no baseline for computation of NNT, it fails to differentiate treatment effect in the absolute scale. In contrast, RNT conveys more information than NNT due to its reversed order of differencing and inverting. For survival endpoints, two versions of RNT calculated as the difference of the reciprocals of survival rates and RMSTs are complementary to each other. The RMST-based RNT can capture the entire follow-up profile and thus is clinically more intuitive and meaningful, as it inherits the time-to-event characteristics for survival endpoints instead of using truncated binary endpoints at a specific time point.ConclusionsThe RNT can serve as an alternative measure for quantifying treatment effect in RCTs, which complements NNT to help patients and clinicians better understand the magnitude of treatment benefit.
| S-EPMC7945324 | biostudies-literature
Project description:The activity of a number of 1-[3-(4-arylpiperazin-1-yl)propyl]pyrrolidin-2-one antiarrhythmic (AA) agents was described using the quantitative structure-activity relationship model by applying it to 33 compounds. The molecular descriptors of the AA activity were obtained by quantum chemical calculations combined with molecular modeling calculations. The resulting model explains up to 91% of the variance and it was successfully validated by four tests (LOO, LMO, external test, and Y-scrambling test). Statistical analysis shows that the AA activity of the studied compounds depends mainly on the PCR and JGI4 descriptors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00044-010-9540-x) contains supplementary material, which is available to authorized users.
| S-EPMC3265727 | biostudies-literature
Project description:BackgroundHealth inequalities, worse health associated with social and economic disadvantage, are reported by a minority of research articles. Locating these studies when conducting an equity-focused systematic review is challenging due to a deficit in standardised terminology, indexing, and lack of validated search filters. Current reporting guidelines recommend not applying filters, meaning that increased resources are needed at the screening stage.MethodsWe aimed to design and test search filters to locate studies that reported outcomes by a social determinant of health. We developed and expanded a 'specific terms strategy' using keywords and subject headings compiled from recent systematic reviews that applied an equity filter. A 'non-specific strategy' was compiled from phrases used to describe equity analyses that were reported in titles and abstracts, and related subject headings. Gold standard evaluation and validation sets were compiled. The filters were developed in MEDLINE, adapted for Embase and tested in both. We set a target of 0.90 sensitivity (95% CI; 0.84, 0.94) in retrieving 150 gold standard validation papers. We noted the reduction in the number needed to screen in a proposed equity-focused systematic review and the proportion of equity-focused reviews we assessed in the project that applied an equity filter to their search strategy.ResultsThe specific terms strategy filtered out 93-95% of all records, and retrieved a validation set of articles with a sensitivity of 0.84 in MEDLINE (0.77, 0.89), and 0.87 (0.81, 0.92) in Embase. When combined (Boolean 'OR') with the non-specific strategy sensitivity was 0.92 (0.86, 0.96) in MEDLINE (Embase 0.94; 0.89, 0.97). The number needed to screen was reduced by 77% by applying the specific terms strategy, and by 59.7% (MEDLINE) and 63.5% (Embase) by applying the combined strategy. Eighty-one per cent of systematic reviews filtered studies by equity.ConclusionsA combined approach of using specific and non-specific terms is recommended if systematic reviewers wish to filter studies for reporting outcomes by social determinants. Future research should concentrate on the indexing standardisation for equity studies and further development and testing of both specific and non-specific terms for accurate study retrieval.
| S-EPMC6186133 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to develop a quantitative framework to estimate the likelihood of multifocal epilepsy based on the number of unifocal seizures observed in the epilepsy monitoring unit (EMU).MethodsPatient records from the EMU at Massachusetts General Hospital (MGH) from 2012 to 2014 were assessed for the presence of multifocal seizures as well the presence of multifocal interictal discharges and multifocal structural imaging abnormalities during the course of the EMU admission. Risk factors for multifocal seizures were assessed using sensitivity and specificity analysis. A Kaplan-Meier survival analysis was used to estimate the risk of multifocal epilepsy for a given number of consecutive seizures. To overcome the limits of the Kaplan-Meier analysis, a parametric survival function was fit to the EMU subjects with multifocal seizures and this was used to develop a Bayesian model to estimate the risk of multifocal seizures during an EMU admission.ResultsMultifocal interictal discharges were a significant predictor of multifocal seizures within an EMU admission with a p < 0.01, albeit with only modest sensitivity 0.74 and specificity 0.69. Multifocal potentially epileptogenic lesions on MRI were not a significant predictor p = 0.44. Kaplan-Meier analysis was limited by wide confidence intervals secondary to significant patient dropout and concern for informative censoring. The Bayesian framework provided estimates for the number of unifocal seizures needed to predict absence of multifocal seizures. To achieve 90% confidence for the absence of multifocal seizure, three seizures are needed when the pretest probability for multifocal epilepsy is 20%, seven seizures for a pretest probability of 50%, and nine seizures for a pretest probability of 80%.SignificanceThese results provide a framework to assist clinicians in determining the utility of trying to capture a specific number of seizures in EMU evaluations of candidates for epilepsy surgery.
| S-EPMC4877132 | biostudies-literature
Project description:ObjectiveSchizophrenia clinical trials commonly measure observed changes in Positive and Negative Syndrome Scale (PANSS) total score. However, it is more intuitive to think of response vs nonresponse, a binary outcome. Assessing binary outcomes enables calculation of number needed to treat (NNT) for therapeutic outcomes, number needed to harm (NNH) for adverse outcomes, and likelihood to be helped or harmed (LHH) to demonstrate benefit/risk tradeoffs. Here, NNT, NNH, and LHH were used to evaluate the clinical usefulness of aripiprazole lauroxil in patients with an acute schizophrenia exacerbation.MethodsCategorical efficacy and tolerability data were taken from the pivotal Phase 3 trial evaluating aripiprazole lauroxil for treatment of an acute exacerbation of schizophrenia. NNT and NNH values, with 95% CIs, were calculated in this post hoc analysis.ResultsUsing the intent-to-treat population for the pooled doses of aripiprazole lauroxil (441 mg [n=196] and 882 mg [n=204] q4w), responder rates (≥30% improvement from baseline PANSS total score) were 35.3% for aripiprazole lauroxil arms vs 18.4% for placebo (n=196), yielding a NNT of 6 (95% CI: 5-11). Discontinuation rates due to adverse events (AEs) were higher among patients randomized to placebo than to either aripiprazole lauroxil dose. Akathisia was the only AE with an incidence ≥5% in each aripiprazole lauroxil group and at least twice that of placebo (11.6%, 11.5%, and 4.3% of the patients receiving aripiprazole lauroxil 441 mg, 882 mg, and placebo, respectively), producing a NNH of 14 (95% CI: 9-33) for pooled aripiprazole lauroxil doses vs placebo. Calculating LHH for therapeutic response vs akathisia, aripiprazole lauroxil was 2.3 times more likely to result in a therapeutic response than an incident of akathisia.ConclusionUsing metrics of NNT, NNH, and LHH, aripiprazole lauroxil was an efficacious and well-tolerated intervention in a pivotal study in patients with an acute schizophrenia exacerbation.
| S-EPMC6751763 | biostudies-literature
Project description:In the rapidly evolving field of spinal cord stimulation (SCS), measures of treatment effects are needed to help understand the benefits of new therapies. The present article elaborates the number needed to treat (NNT) concept and applies it to the SCS field. We reviewed the basic theory of the NNT, its calculation method, and its application to historical controlled trials of SCS. We searched the literature for controlled studies with ≥20 implanted SCS patients with chronic axial back and/or leg pain followed for ≥3 months and a reported responder rate defined as ≥50% pain relief. Relevant data necessary to estimate the NNT were extracted from the included articles. In total, 12 of 1616 records were eligible for inclusion. The records reported 10 clinical studies, including 7 randomized controlled trials, 2 randomized crossover trials, and 1 controlled cohort study. The studies investigated traditional SCS and more recently developed SCS modalities, including 10 kHz SCS. In conclusion, the NNT estimate may help SCS stakeholders better understand the effect size difference between compared treatments; however, interpretation of any NNT should take into account its full context. In addition, comparisons across trials of different therapies should be avoided since they are prone to interpretation biases.
| S-EPMC8962384 | biostudies-literature
Project description:Clinicians are expected to select a therapy based on their appraisal of evidence on benefit-to-risk profiles of therapies. In the management of relapsing-remitting multiple sclerosis (RRMS), evidence is typically expressed in terms of risk (proportion) of event, risk reduction, relative and hazard rate reduction, or relative reduction in the mean number of magnetic resonance imaging lesions. Interpreting treatment effect using these measures from a RRMS clinical trial is fairly reliable; however, this might not be the case when treatment effect is expressed in terms of the number needed to treat (NNT). The objective of this review is to discuss the utility of NNT in RRMS trials. This article presents an overview of the methodological definition and characteristics of NNT as well as the relative merit of NNT use in RRMS controlled clinical trials, where endpoints are typically time-to-event and frequency of recurrent events. The authors caution against using NNT in multiple sclerosis, a clinically heterogeneous disease that can change course and severity unpredictably. The authors also caution against the use of NNT to interpret results in comparative trials where the absolute risk difference is not statistically significant, computing NNT using the time-to-event endpoint at intermediate time points, computing NNT using the annualized relapse rate, and comparing NNT across trials.
| S-EPMC5447556 | biostudies-literature