NICE hears appeals over dementia drugs.
Ontology highlight
ABSTRACT:
SUBMITTER: Kmietowicz Z
PROVIDER: S-EPMC1513446 | biostudies-literature | 2006 Jul
REPOSITORIES: biostudies-literature
Publications
NICE hears appeals over dementia drugs.
BMJ (Clinical research ed.) 20060701 7560
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Project description:BackgroundThe National Institute for Health and Care Excellence (NICE) pioneered the Health Technology Assessment (HTA) processes and methodologies. Technology appraisals (TAs) focus on pharmaceutical products and clinical and economic data, which are presented by the product manufacturers to the NICE appraisal committee for decision-making. Uncertainty in data reduces the chance of a positive outcome from the HTA process or requires a higher discount.ObjectiveTo investigate the quality of clinical data (comparator, quality of life (QoL), randomised controlled trials (RCTs) and overall quality of evidence) submitted by the manufacturers to NICE.DesignThis retrospective evaluation analysed active TAs published between 2000 and 2019 (up to TA600).MethodsFor all TAs, we extracted data from the Assessment Group and Evidence Review Group reports and Final Appraisal Determinations on (1) the quality of submitted RCTs and (2) the overall quality of evidence submitted for decision-making. For single TAs, we also extracted data and its critique on QoL and comparators. Each category was scored for quality and analysed using descriptive statistics.Results409 TAs were analysed (multiple technology appraisals (MTA)=104, single technology appraisal (STA)=305). In two-thirds of TAs, the overall quality of evidence was either poor (n=224, 55%) or unacceptable (n=41, 10%). In 39% (n=119) of the STAs, the quality of comparative evidence was considered poor, and in 17% (n=51) unacceptable. In 44% (n=135) of STAs, the quality of QoL data was considered poor, 15% (n=47) unacceptable, 33% (n=102) acceptable and 7% (n=21) as good. Over 20 years of longitudinal analysis did not show improvements in the quality of evidence submitted to NICE.ConclusionWe found that the primary components of clinical evidence influencing NICE's decision-making framework were of poor quality. It is essential to continue to generate robust clinical data for premarket and postmarket introduction of medicines into clinical practice to ensure they deliver benefits to patients.
| S-EPMC10870012 | biostudies-literature
Project description:ObjectiveThis study examined the application, feasibility, and validity of supervised learning models for text classification in appraisals for rare disease treatments (RDTs) in relation to uncertainty, and analyzed differences between appraisals based on the classification results.MethodsWe analyzed appraisals for RDTs (n = 94) published by the National Institute for Health and Care Excellence (NICE) between January 2011 and May 2023. We used Naïve Bayes, Lasso, and Support Vector Machine models in a binary text classification task (classifying paragraphs as either referencing uncertainty in the evidence base or not). To illustrate the results, we tested hypotheses in relation to the appraisal guidance, advanced therapy medicinal product (ATMP) status, disease area, and age group.ResultsThe best performing (Lasso) model achieved 83.6 percent classification accuracy (sensitivity = 74.4 percent, specificity = 92.6 percent). Paragraphs classified as referencing uncertainty were significantly more likely to arise in highly specialized technology (HST) appraisals compared to appraisals from the technology appraisal (TA) guidance (adjusted odds ratio = 1.44, 95 percent CI 1.09, 1.90, p = 0.004). There was no significant association between paragraphs classified as referencing uncertainty and appraisals for ATMPs, non-oncology RDTs, and RDTs indicated for children only or adults and children. These results were robust to the threshold value used for classifying paragraphs but were sensitive to the choice of classification model.ConclusionUsing supervised learning models for text classification in NICE appraisals for RDTs is feasible, but the results of downstream analyses may be sensitive to the choice of classification model.
| S-EPMC10859832 | biostudies-literature
Project description:Here, we compile the Biopharmaceutics Drug Disposition Classification System (BDDCS) classification for 927 drugs, which include 30 active metabolites. Of the 897 parent drugs, 78.8% (707) are administered orally. Where the lowest measured solubility is found, this value is reported for 72.7% (513) of these orally administered drugs and a dose number is recorded. The measured values are reported for percent excreted unchanged in urine, LogP, and LogD (7.4) when available. For all 927 compounds, the in silico parameters for predicted Log solubility in water, calculated LogP, polar surface area, and the number of hydrogen bond acceptors and hydrogen bond donors for the active moiety are also provided, thereby allowing comparison analyses for both in silico and experimentally measured values. We discuss the potential use of BDDCS to estimate the disposition characteristics of novel chemicals (new molecular entities) in the early stages of drug discovery and development. Transporter effects in the intestine and the liver are not clinically relevant for BDDCS class 1 drugs, but potentially can have a high impact for class 2 (efflux in the gut, and efflux and uptake in the liver) and class 3 (uptake and efflux in both gut and liver) drugs. A combination of high dose and low solubility is likely to cause BDDCS class 4 to be underpopulated in terms of approved drugs (N?=?53 compared with over 200 each in classes 1-3). The influence of several measured and in silico parameters in the process of BDDCS category assignment is discussed in detail.
| S-EPMC3231854 | biostudies-other
Project description:Alzheimer's disease and related dementias (ADRD) remain a major health-care challenge with few licensed medications. Repurposing existing drugs may afford prevention and treatment. Phosphodiesterase-5 (PDE5) is widely expressed in vascular myocytes, neurons, and glia. Potent, selective, Food and Drug Administration-approved PDE5 inhibitors are already in clinical use (sildenafil, vardenafil, tadalafil) as vasodilators in erectile dysfunction and pulmonary arterial hypertension. Animal data indicate cognitive benefits of PDE5 inhibitors. In humans, real-world patient data suggest that sildenafil and vardenafil are associated with reduced dementia risk. While a recent clinical trial of acute tadalafil on cerebral blood flow was neutral, there may be chronic actions of PDE5 inhibition on cerebrovascular or synaptic function. We provide a perspective on the potential utility of PDE5 inhibitors for ADRD. We conclude that further prospective clinical trials with PDE5 inhibitors are warranted. The choice of drug will depend on brain penetration, tolerability in older people, half-life, and off-target effects.HighlightsPotent phosphodiesterase-5 (PDE5) inhibitors are in clinical use as vasodilators.In animals PDE5 inhibitors enhance synaptic function and cognitive ability.In humans the PDE5 inhibitor sildenafil is associated with reduced risk of Alzheimer's disease.Licensed PDE5 inhibitors have potential for repurposing in dementia.Prospective clinical trials of PDE5 inhibitors are warranted.
| S-EPMC10520293 | biostudies-literature
Project description: Not available
| S-EPMC11612831 | biostudies-literature
Project description:IntroductionMultimorbidity is associated with increased risk of dementia, but previous estimation of the joint contribution of constituent conditions to dementia incidence did not model additive contributions or temporal proximity in the sequential onset of conditions.MethodsData were analyzed from 9944 Health and Retirement Study participants and Medicare fee-for-service beneficiaries, ages 68-99, without Alzheimer's disease and related dementias (ADRD) at baseline, from 1998-2016. ADRD and chronic condition were encoded using validated claims algorithms. We estimated the absolute contribution of eight conditions to ADRD with the longitudinal extension of the average attributable fraction (LE-AAF).ResultsHypertension, acute myocardial infarction, atrial fibrillation, diabetes, heart failure, ischemic heart disease, stroke, and arthritis additively accounted for 71.8% (95% confidence interval [CI]: 62.9%-79.1%) of ADRD incident cases based on LE-AAF.DiscussionOur findings suggest that multimorbidity plays a pivotal role in ADRD incidence. Targeting constituents of a cardiovascular path to dementia may contribute most to lowering dementia risk.HighlightsMost dementia cases (71.8%) were attributable to eight chronic conditions. Hypertension was the largest contributor to dementia risk. Confidence intervals were smallest for constituents of a cardiovascular path to dementia. Longitudinal extension of the average attributable fractions (LE-AAFs) explicitly consider longitudinal patterns of comorbidities. Acute myocardial infarction did not contribute significantly to dementia incidence.
| S-EPMC11847647 | biostudies-literature
Project description:What do we hear when someone speaks and what does auditory cortex (AC) do with that sound? Given how meaningful speech is, it might be hypothesized that AC is most active when other people talk so that their productions get decoded. Here, neuroimaging meta-analyses show the opposite: AC is least active and sometimes deactivated when participants listened to meaningful speech compared to less meaningful sounds. Results are explained by an active hypothesis-and-test mechanism where speech production (SP) regions are neurally re-used to predict auditory objects associated with available context. By this model, more AC activity for less meaningful sounds occurs because predictions are less successful from context, requiring further hypotheses be tested. This also explains the large overlap of AC co-activity for less meaningful sounds with meta-analyses of SP. An experiment showed a similar pattern of results for non-verbal context. Specifically, words produced less activity in AC and SP regions when preceded by co-speech gestures that visually described those words compared to those words without gestures. Results collectively suggest that what we 'hear' during real-world speech perception may come more from the brain than our ears and that the function of AC is to confirm or deny internal predictions about the identity of sounds.
| S-EPMC4123676 | biostudies-literature
Project description:Purpose of the studyAge-related hearing loss negatively affects health outcomes, yet disparities in hearing care, such as hearing aid use, exist based on race/ethnicity and socioeconomic position. Recent national efforts highlight reduction of hearing care disparities as a public health imperative. This study a) describes a community engagement approach to addressing disparities, b) reports preliminary outcomes of a novel intervention, and c) discusses implementation processes and potential for wide-scale testing and use.Design and methodsThis was a prospective, randomized control pilot, with a 3-month delayed treatment group as a waitlist control, that assessed feasibility, acceptability, and preliminary efficacy of a community-delivered, affordable, and accessible intervention for older adults with hearing loss. Outcomes were assessed at 3 months, comparing immediate and delayed groups, and pooled to compare the cohort's pre- and 3-month post-intervention results.ResultsAll participants completed the study (n = 15). The program was highly acceptable: 93% benefited, 100% would recommend the program, and 67% wanted to serve as future program trainers. At 3 months, the treated group (n = 8) experienced fewer social and emotional effects of hearing loss and fewer depressive symptoms as compared to the delayed treatment group (n = 7). Pooling 3-month post-intervention scores (n = 15), participants reported fewer negative hearing-related effects (effect size = -0.96) and reduced depressive symptoms (effect size = -0.43).ImplicationsThe HEARS (Hearing Equality through Accessible Research & Solutions) intervention is feasible, acceptable, low risk, and demonstrates preliminary efficacy. HEARS offers a novel, low-cost, and readily scalable solution to reduce hearing care disparities and highlights how a community-engaged approach to intervention development can address disparities.
| S-EPMC5881797 | biostudies-literature
Project description:ObjectivesTo estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia.DesignCase-control study.SettingGeneral practices in the UK contributing to the Clinical Practice Research Datalink.Participants40 770 patients aged 65-99 with a diagnosis of dementia between April 2006 and July 2015, and 283 933 controls without dementia.InterventionsDaily defined doses of anticholinergic drugs coded using the Anticholinergic Cognitive Burden (ACB) scale, in total and grouped by subclass, prescribed 4-20 years before a diagnosis of dementia.Main outcome measuresOdds ratios for incident dementia, adjusted for a range of demographic and health related covariates.Results14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11 (95% confidence interval 1.08 to 1.14). Dementia was associated with an increasing average ACB score. When considered by drug class, gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia. The risk of dementia increased with greater exposure for antidepressant, urological, and antiparkinson drugs with an ACB score of 3. This result was also observed for exposure 15-20 years before a diagnosis.ConclusionsA robust association between some classes of anticholinergic drugs and future dementia incidence was observed. This could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia. Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure.Trial registrationRegistered to the European Union electronic Register of Post-Authorisation Studies EUPAS8705.
| S-EPMC5915701 | biostudies-literature
Project description:Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2'-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2'-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide.
| S-EPMC4978613 | biostudies-literature