Epilepsy-related stigma and attitudes: Systematic review of screening instruments and interventions - Report by the International League Against Epilepsy Task Force on Stigma in Epilepsy.

OBJECTIVE: This is a systematic review aimed at summarizing the evidence related to instruments that have been developed to measure stigma or attitudes toward epilepsy and on stigma-reducing interventions. METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. A broad literature search (1985-2019) was performed in 13 databases. Articles were included if they described the development and testing of psychometric properties of an epilepsy-related stigma or attitude scale or stigma-reducing interventions. Two reviewers independently screened abstracts, reviewed full-text articles, and extracted data. Basic descriptive statistics are reported. RESULTS: We identified 4234 abstracts, of which 893 were reviewed as full-text articles. Of these, 38 met inclusion criteria for an instrument development study and 30 as a stigma-reduction intervention study. Most instruments were initially developed using well-established methods and were tested in relatively large samples. Most intervention studies involved educational programs for adults with pre- and post-evaluations of attitudes toward people with epilepsy. Intervention studies often failed to use standardized instruments to quantify stigmatizing attitudes, were generally underpowered, and often found no evidence of benefit or the benefit was not sustained. Six intervention studies with stigma as the primary outcome had fewer design flaws and showed benefit. Very few or no instruments were validated for regional languages or culture, and there were very few interventions tested in some regions. SIGNIFICANCE: Investigators in regions without instruments should consider translating and further developing existing instruments rather than initiating the development of new instruments. Very few stigma-reduction intervention studies for epilepsy have been conducted, study methodology in general was poor, and standardized instruments were rarely used to measure outcomes. To accelerate the development of effective epilepsy stigma-reduction interventions, a paradigm shift from disease-specific, siloed trials to collaborative, cross-disciplinary platforms based upon unified theories of stigma transcending individual conditions will be needed.

Systematic review of frequency of felt and enacted stigma in epilepsy and determining factors and attitudes toward persons living with epilepsy-Report from the International League Against Epilepsy Task Force on Stigma in Epilepsy.

OBJECTIVE: To review the evidence of felt and enacted stigma and attitudes toward persons living with epilepsy, and their determining factors. METHODS: Thirteen databases were searched (1985-2019). Abstracts were reviewed in duplicate and data were independently extracted using a standardized form. Studies were characterized using descriptive analysis by whether they addressed "felt" or "enacted" stigma and "attitudes" toward persons living with epilepsy. RESULTS: Of 4234 abstracts, 132 met eligibility criteria and addressed either felt or enacted stigma and 210 attitudes toward epilepsy. Stigma frequency ranged broadly between regions. Factors associated with enacted stigma included low level of knowledge about epilepsy, lower educational level, lower socioeconomic status, rural areas living, and religious grouping. Negative stereotypes were often internalized by persons with epilepsy, who saw themselves as having an "undesirable difference" and so anticipated being treated differently. Felt stigma was associated with increased risk of psychological difficulties and impaired quality of life. Felt stigma was linked to higher seizure frequency, recency of seizures, younger age at epilepsy onset or longer duration, lower educational level, poorer knowledge about epilepsy, and younger age. An important finding was the potential contribution of epilepsy terminology to the production of stigma. Negative attitudes toward those with epilepsy were described in 100% of included studies, and originated in any population group (students, teachers, healthcare professionals, general public, and those living with epilepsy). Better attitudes were generally noted in those of younger age or higher educational status. SIGNIFICANCE: Whatever the specific beliefs about epilepsy, implications for felt and enacted stigma show considerable commonality worldwide. Although some studies show improvement in attitudes toward those living with epilepsy over time, much work remains to be done to improve attitudes and understand the true occurrence of discrimination against persons with epilepsy.

What really matters? A mixed methods study of treatment preferences and priorities among people with epilepsy in the UK.

The widening range of treatment options for epilepsy, and their potential outcomes, mean decisions about treatment for people with epilepsy (PWE) are often complex. While antiepileptic drugs (AEDs) represent the mainstay of treatment, other potential nondrug interventions are gaining in importance. These treatments all have the potential for harming those using them, as well as bringing benefits. This study examined the views and experiences of PWE about a range of treatment options. We used both qualitative and quantitative approaches - a series of depth-narrative interviews, followed by a large-scale survey. Treatment options and healthcare priorities deemed important by at least 10% of interview participants were then addressed as a series of statements in the follow-on survey questionnaire. Quantitative responses supported healthcare priorities identified through the qualitative interviews. The key goal of treatment among study participants was to be able to live 'a normal life'. Important physical, psychological, and life benefits of treatment were identified - most being the direct consequence of improved seizure control. One psychological benefit, reduced worry, was also identified as an important treatment goal. All participants viewed AEDs as appropriate first-line treatment; and since adverse effects of AEDs had implications for individual levels of daily function and wellbeing, their appropriate management was considered important. In contrast, surgery was almost always regarded as the treatment of last resort. Despite lack of research evidence supporting their use, participants were interested in complementary therapies as adjunctive treatment and a means of coping with having epilepsy, with yoga and meditation of particular interest. An important finding was the desire for targeted services to help with memory problems, as was the call to increase availability of psychological/counseling services. Our findings emphasize the importance of providing treatment responsive to the life context of individual patients. They highlight not only the level of demand for specific treatment options, but also the need for high-quality evidence to support future investment in their provision.

Patient-Focused Drug Development Methods for Benefit-Risk Assessments: A Case Study Using a Discrete Choice Experiment for Antiepileptic Drugs.

Regulatory decisions may be enhanced by incorporating patient preferences for drug benefit and harms. This study demonstrates a method of weighting clinical evidence by patients' benefit-risk preferences. Preference weights, derived from discrete choice experiments, were applied to clinical trial data to estimate the expected utility of alternative drugs. In a case study, the rank ordering of antiepileptic drugs (AEDs), as indicated from clinical studies, was compared with ordering based on weighting clinical evidence by patients' preferences. A statistically significant change in rank ordering of AEDs was observed for women of childbearing potential who were prescribed monotherapy for generalized or unclassified epilepsy. Rank ordering inferred from trial data, valproate > topiramate > lamotrigine, was reversed. Modeling the expected utility of drugs might address the need to use more systematic, methodologically sound approaches to collect patient input that can further inform regulatory decision making.

Does the concept of resilience contribute to understanding good quality of life in the context of epilepsy?

A significant body of research highlights negative impacts of epilepsy for individual quality of life (QOL). Poor seizure control is frequently associated with reporting of poor QOL and good seizure control with good QOL; however, this is not a universal finding. Evidence suggests that some people enjoy good QOL despite ongoing seizures while others report poor QOL despite good seizure control. Understanding the factors that influence QOL for people with epilepsy and the processes via which such factors exert their influence is central to the development of interventions to support people with epilepsy to experience the best possible QOL. We present findings of a qualitative investigation exploring influences and processes on QOL for people with epilepsy. We describe the clinical, psychological, and social factors contributing to QOL. In particular, we focus on the value of the concept of resilience for understanding quality of life in epilepsy. Based on our analysis, we propose a model of resilience wherein four key component sets of factors interact to determine QOL. This model reflects the fluid nature of resilience that, we suggest, is subject to change based on shifts within the individual components and the interactions between them. The model offers a representation of the complex influences that act and interact to either mitigate or further compound the negative impacts of epilepsy on individual QOL.

Pharmacogenetic testing prior to carbamazepine treatment of epilepsy: patients' and physicians' preferences for testing and service delivery.

AIM: Pharmacogenetic studies have identified the presence of the HLA-A*31:01 allele as a predictor of cutaneous adverse drugs reactions (ADRs) to carbamazepine. This study aimed to ascertain the preferences of patients and clinicians to inform carbamazepine pharmacogenetic testing services. METHODS: Attributes of importance to people with epilepsy and neurologists were identified through interviews and from published sources. Discrete choice experiments (DCEs) were conducted in 82 people with epilepsy and 83 neurologists. Random-effects logit regression models were used to determine the importance of the attributes and direction of effect. RESULTS: In the patient DCE, all attributes (seizure remission, reduction in seizure frequency, memory problems, skin rash and rare, severe ADRs) were significant. The estimated utility of testing was greater, at 0.52 (95% CI 0.19, 1.00) than not testing at 0.33 (95% CI -0.07, 0.81). In the physician DCE, cost, inclusion in the British National Formulary, coverage, negative predictive value (NPV) and positive predictive value (PPV) were significant. Marginal rates of substitution indicated that neurologists were willing to pay £5.87 for a 1 percentage point increase in NPV and £3.99 for a 1 percentage point increase in PPV. CONCLUSION: The inclusion of both patients' and clinicians' perspectives represents an important contribution to the understanding of preferences towards pharmacogenetic testing prior to initiating carbamazepine. Both groups identified different attributes but had generally consistent preferences. Patients' acceptance of a decrease in treatment benefit for a reduced chance of severe ADRs adds support for the implementation of HLA-A*31:01 testing in routine practice.

The natural history of conducting and reporting clinical trials: interviews with trialists.

BACKGROUND: To investigate the nature of the research process as a whole, factors that might influence the way in which research is carried out, and how researchers ultimately report their findings. METHODS: Semi-structured qualitative telephone interviews with authors of trials, identified from two sources: trials published since 2002 included in Cochrane systematic reviews selected for the ORBIT project; and trial reports randomly sampled from 14,758 indexed on PubMed over the 12-month period from August 2007 to July 2008. RESULTS: A total of 268 trials were identified for inclusion, 183 published since 2002 and included in the Cochrane systematic reviews selected for the ORBIT project and 85 randomly selected published trials indexed on PubMed. The response rate from researchers in the former group was 21% (38/183) and in the latter group was 25% (21/85). Overall, 59 trialists were interviewed from the two different sources. A number of major but related themes emerged regarding the conduct and reporting of trials: establishment of the research question; identification of outcome variables; use of and adherence to the study protocol; conduct of the research; reporting and publishing of findings. Our results reveal that, although a substantial proportion of trialists identify outcome variables based on their clinical experience and knowing experts in the field, there can be insufficient reference to previous research in the planning of a new trial. We have revealed problems with trial recruitment: not reaching the target sample size, over-estimation of recruitment potential and recruiting clinicians not being in equipoise. We found a wide variation in the completeness of protocols, in terms of detailing study rationale, outlining the proposed methods, trial organisation and ethical considerations. CONCLUSION: Our results confirm that the conduct and reporting of some trials can be inadequate. Interviews with researchers identified aspects of clinical research that can be especially challenging: establishing appropriate and relevant outcome variables to measure, use of and adherence to the study protocol, recruiting of study participants and reporting and publishing the study findings. Our trialists considered the prestige and impact factors of academic journals to be the most important criteria for selecting those to which they would submit manuscripts.

Quality-of-life outcomes of initiating treatment with standard and newer antiepileptic drugs in adults with new-onset epilepsy: findings from the SANAD trial.

OBJECTIVE: To compare quality-of-life (QoL) outcomes over 2 years following initiation of treatment with a standard or newer antiepileptic drug (AED) in adults with new-onset epilepsy. To examine the impact of seizure remission and failure of initial treatment on QoL outcomes measured over 2 years. METHODS: We conducted a pragmatic, randomized, unblinded, multicenter, parallel-group clinical trial (the Standard and New Antiepileptic Drugs [SANAD] trial) comparing clinical and cost effectiveness of initiating treatment with carbamazepine versus lamotrigine, gabapentin, oxcarbazepine and topiramate, and valproate versus lamotrigine and topiramate. QoL data were collected by mail at baseline, 3 months, and at 1 and 2 years using validated measures. These data were analyzed using longitudinal data models. Continuous QoL measures, time to 12-month remission and time to treatment withdrawal were explored using joint models. RESULTS: Baseline questionnaires were returned by 1,575 adults; 1,439 returned the 3-month questionnaire, 1,274 returned the 1-year questionnaire, and 1,121 returned the 2-year questionnaire. There were few statistically significant differences between drugs over 2 years in QoL outcomes. Significant association was identified between QoL scores over the 2-year time frame and the risk of experiencing a 12-month remission or treatment withdrawal over that period. SIGNIFICANCE: The choice of initial treatment had no significant effect on QoL by 2-year follow-up. However, overall QoL was reduced with continued seizures, adverse events, and failure of the initial treatment.

Self-reported anxiety and sleep problems in people with epilepsy and their association with quality of life.

Comorbidities are common in epilepsy, and their role in quality of life (QOL) is receiving increasing scrutiny. Considerable attention has been focused on the role of depression, the most common comorbidity, with rather less attention paid to its frequent concomitant, anxiety, and other conditions known to be at increased prevalence among people with epilepsy (PWE) when compared to the general population. In this paper, we report findings from a UK-based survey in which we examined self-reporting of two common comorbidities, anxiety and sleep problems, factors associated with them, and their role in QOL in people with and without epilepsy. Data were obtained via mailed questionnaires, supplemented by an internet survey, from PWE and age- and gender-matched controls. Based on self-reported symptoms, PWE were at higher risk of anxiety and sleep problems. Contributory factors for anxiety included poorer general health, worry about seizures, and self-reported antiepileptic drug (AED) side effects. Good social support emerged as protective for anxiety in PWE. Nighttime sleep problems were very common even in controls but were further elevated in PWE. Antiepileptic drug adverse events emerged as an important contributory factor for sleep problems. Trait anxiety emerged as significant for defining overall QOL, and its importance over state anxiety supports the notion of anxiety in PWE as a primarily premorbid condition. In contrast, sleep quality was not consistently predictive of QOL. Our study has important implications for clinical management, emphasizing the need for a holistic approach to address wider patient-reported problems as well as any epilepsy-specific ones.

Values associated with public involvement in health and social care research: a narrative review.

BACKGROUND: Much has been written about public involvement (PI) in health and social care research, but underpinning values are rarely made explicit despite the potential for these to have significant influence on the practice and assessment of PI. OBJECTIVE: The narrative review reported here is part of a larger MRC-funded study which is producing a framework and related guidance on assessing the impact of PI in health and social care research. The review aimed to identify and characterize the range of values associated with PI that are central elements of the framework. METHODS: We undertook a review and narrative synthesis of diverse literatures of PI in health and social care research, including twenty existing reviews and twenty-four chapters in sixteen textbooks. RESULTS: Three overarching value systems were identified, each containing five value clusters. (i) A system concerned with ethical and/or political issues including value clusters associated with empowerment; change/action; accountability/transparency; rights; and ethics (normative values). (ii). A system concerned with the consequences of public involvement in research including value clusters associated with effectiveness; quality/relevance; validity/reliability; representativeness/objectivity/generalizability; and evidence (substantive values). (iii) A system concerned with the conduct of public involvement in including value clusters associated with Partnership/equality; respect/trust; openness and honesty; independence; and clarity (process values). CONCLUSION: Our review identified three systems associated with PI in health and social care research focused on normative, substantive and process values. The findings suggest that research teams should consider and make explicit the values they attach to PI in research and discuss ways in which potential tensions may be managed in order to maximize the benefits of PI for researchers, lay experts and the research.

Exploring perceived barriers, drivers, impacts and the need for evaluation of public involvement in health and social care research: a modified Delphi study.

OBJECTIVE: To explore areas of consensus and conflict in relation to perceived public involvement (PI) barriers and drivers, perceived impacts of PI and ways of evaluating PI approaches in health and social care research. BACKGROUND: Internationally and within the UK the recognition of potential benefits of PI in health and social care research is gathering momentum and PI is increasingly identified by organisations as a prerequisite for funding. However, there is relatively little examination of the impacts of PI and how those impacts might be measured. DESIGN: Mixed method, three-phase, modified Delphi technique, conducted as part of a larger MRC multiphase project. SAMPLE: Clinical and non-clinical academics, members of the public, research managers, commissioners and funders. FINDINGS: This study found high levels of consensus about the most important barriers and drivers to PI. There was acknowledgement that tokenism was common in relation to PI; and strong support for the view that demonstrating the impacts and value of PI was made more difficult by tokenistic practice. PI was seen as having intrinsic value; nonetheless, there was clear support for the importance of evaluating its impact. Research team cohesion and appropriate resources were considered essential to effective PI implementation. Panellists agreed that PI can be challenging, but can be facilitated by clear guidance, together with models of good practice and measurable standards. CONCLUSIONS: This study is the first to present empirical evidence of the opinions voiced by key stakeholders on areas of consensus and conflict in relation to perceived PI barriers and drivers, perceived impacts of PI and the need to evaluate PI. As such it further contributes to debate around best practice in PI, the potential for tokenism and how best to evaluate the impacts of PI. These findings have been used in the development of the Public Involvement Impact Assessment Framework (PiiAF), an online resource which offers guidance to researchers and members of the public involved in the PI process.

Valuations of epilepsy-specific health states: a comparison of patients with epilepsy and the general population.

AIMS: Utility values that can be used in the economic evaluation of treatments for epilepsy can be elicited from the general population and the patient population, but it is unclear how the health state values differ. The aim of this study is to compare the preferences of the general population and a sample of people with epilepsy for health states described by the NEWQOL-6D QALY measure. METHODS: The Time Trade Off preference elicitation technique was used to value eight NEWQOL-6D health states. The general population sample was recruited and interviewed in their homes, and the sample with epilepsy was recruited and interviewed in an epilepsy service in North West England. Descriptive analysis and regression modeling were used to compare health state values across the populations. RESULTS: A sample of 70 people with epilepsy and a sample of 60 members of the general population were included. The populations differed across a range of background characteristics, but there were limited differences between the health state values. Patients provided significantly higher (better) values for the most severe health state described by the NEWQOL-6D (p<0.01) and nonsignificant higher values for states with intermediate severity. The general population health state value was only higher for the best health state described by the NEWQOL-6D. CONCLUSIONS: The similarities in the patient and general population values for NEWQOL-6D health states suggest that the use of the general population utility weights for the estimation of QALYs in the economic evaluation of epilepsy interventions is appropriate and largely representative of patient preferences.

Exploring loss and replacement of loss for understanding the impacts of epilepsy onset: a qualitative investigation.

Previous research identifies loss as a key concept for our understanding of the impact of chronic illness. In this in-depth qualitative study, we explored the utility of the concept of loss and loss replacement as a means of gaining a fuller understanding of the implications of a diagnosis of epilepsy for overall quality of life (QOL). Potential participants were identified from the database of a large UK-based randomized controlled trial of antiepileptic drug treatment for new-onset epilepsy and selected using purposive sampling methods. In-depth interviews were conducted with 67 people; interview material was analyzed thematically. Our findings confirm 'loss' as a key concept in understanding epilepsy impact. Participants cited profound physical and social losses, and the links between these and psychological loss were clearly articulated. Informants described two main processes via which the linked losses they experienced occurred: personal withdrawal processes and externally enforced processes. Seizure control was integral to restoring psychological well-being and a sense of normality but was only one of a number of influences moderating the degree of loss experienced following seizure onset. Our work emphasizes that people with epilepsy (PWE) require active support for their continued engagement or reengagement in roles and activities identified as central to their psychological well-being and overall QOL. Achieving this requires a multiagency approach to drive forward key strategies for reduction of the negative impacts of epilepsy and to engender a sense of normality in the context of a condition often experienced as placing the individual outside the socially determined parameters of the 'normal'.

Stigma in epilepsy.

Stigma remains a weight those with epilepsy have to carry and a defining feature of their identity. This article highlights recent studies published in the area of stigma, knowledge, attitudes, and practices regarding epilepsy. First, recent studies addressing the frequency of stigma and factors associated with stigma are discussed. Second, tools developed to ascertain stigma in epilepsy, or knowledge, attitudes, and practices, are examined. Lastly, we discuss interventions recently studied to reduce stigma in epilepsy.

Factors associated with perceived stigma of epilepsy in Croatia: a study using the revised Epilepsy Stigma Scale.

PURPOSE: It is believed that a large number of factors influence feelings of stigma, but their relative contribution is not yet entirely clear. Most studies to date were conducted using the Epilepsy Stigma Scale (ESS); only one used a revised version of the ESS (rESS). The following study aims to determine factors contributing to epilepsy stigma in outpatients with chronic epilepsy in Croatia, and to analyze some psychometric properties of the Croatian translation of the rESS. METHODS: Alongside standard testing for validity of the scale, a simulation model of the original ESS (smESS) was created. This model, which does not include a grading Likert 0-3 scale, was compared with the rESS. RESULTS: In total, 159 out of 298 subjects (53%) reported feeling stigmatised, with 136 (45%) mild to moderately and 23 (8%) highly. Internal consistency of the Croatian translation of the rESS was 0.887. Feelings of stigma were significantly associated with age ≤ 50 years, younger age of epilepsy onset, more than 50 seizures to date, generalized tonic-clonic seizures, and a shorter seizure-free period. Multiple stepwise regression showed number of seizures to date as a significant variable (Beta=0.246). By adapting data into the smESS significant associations with younger age and age of epilepsy onset were lost. Internal consistency of the smESS was 0.849. CONCLUSIONS: The Croatian translation of the rESS has been proved to be a suitable instrument for diagnosing epilepsy stigma. The results of our model point to the possibility that the rESS might be more sensitive than the original ESS.

Tools for assessing quality of life in epilepsy patients.

In this review, we attempt to bring the reader up to date with recent developments in the area of assessment of quality of life (QOL) of patients with epilepsy, in both the research and clinical contexts. We present evidence from recent publications on the major and most commonly used QOL instruments for both adults and children with epilepsy, including both strengths and limitations. We discuss both generic measures and ones that have been developed specifically for use in the epilepsy population. We draw attention to some of the broader issues that render the QOL assessment endeavor a somewhat complex one - in particular, that epilepsy is not a single condition, with a common clinical trajectory; and that QOL measures as currently configured almost universally focus on its negative impacts, largely neglecting the possibility of those affected being able to retain reasonable social adjustment and life satisfaction. Finally, we suggest that further work needs to focus on plugging the current evidence gaps in relation to psychometric and cross-cultural applicability issues; and on the value of QOL instruments in the clinical care setting. We conclude by highlighting a number of issues from the QOL literature that will, in our view, be the focus of increasing research interest in the next few years.

The reliability and validity of the Revised Liverpool Impact of Epilepsy Scale for use in people with new-onset epilepsy.

The Impact of Epilepsy Scale was designed to assess the perceived impact of epilepsy on a number of different aspects of daily life. Following criticisms of the scale's content and focus, it was revised to incorporate an amended response continuum and additional items. A total of 1534 people with epilepsy completed the revised scale, along with other quality-of-life (QOL) measures, as part of the Standard and New Antiepileptic Drugs (SANAD) trial (Marson et al., 2007a,b) [9,10]. The revised scale had good reliability (internal consistency alpha coefficient of .83) and acceptable validity (concurrent and known-groups). Floor and ceiling effects were negligible. Therefore, the Revised Liverpool Impact of Epilepsy Scale is a reliable and valid instrument for assessing the perceived impact of epilepsy in people with new-onset epilepsy.