BACKGROUND: Poor adherence to antiepileptic medication is associated with increased mortality, morbidity and healthcare costs. In this review, we focus on interventions designed and tested in randomised controlled trials (RCTs) and quasi-RCTs to assist people with adherence to antiepileptic medication. This is an update of a Cochrane review first published in 2011, and last updated in 2017.
OBJECTIVES: To determine the effectiveness of interventions aimed at improving adherence to antiepileptic medication in adults and children with epilepsy.
SEARCH METHODS: For the latest update, we searched the following databases on 18 February 2020: Cochrane Register of Studies (CRS Web), MEDLINE, CINAHL Plus and PsycINFO. CRS Web includes RCTs or quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), CENTRAL, and the Specialized Registers of Cochrane Review Groups including Epilepsy. We also searched the reference lists of relevant articles.
SELECTION CRITERIA: RCTs and quasi-RCTs of adherence-enhancing interventions aimed at people with a clinical diagnosis of epilepsy (as defined in individual studies), of any age and treated with antiepileptic drugs in a primary care, outpatient or other community setting.
DATA COLLECTION AND ANALYSIS: All review authors independently assessed lists of potentially relevant citations and abstracts. At least two review authors independently extracted data and performed a quality assessment of each study according to the Cochrane tool for assessing risk of bias. We graded the level of evidence for each outcome according to GRADE. The studies differed widely according to the type of intervention and measures of adherence; therefore combining data was not appropriate.
MAIN RESULTS: We included 20 studies reporting data on 2832 participants. Thirteen studies targeted adults with epilepsy, one study included participants of all ages, one study included participants older than two years, one recruited pediatric patients aged between 1 month to 15 years, one study targeted caregivers of children with epilepsy, one targeted adolescents and caregivers, and two studies targeted families of children with epilepsy. We identified three ongoing studies. Follow-up time was generally short in most studies, ranging from 1 to 12 months. The studies examined three main types of interventions: educational interventions, behavioural interventions and mixed interventions. All but three studies compared treatment with usual care or 'no intervention'. Due to heterogeneity between studies in terms of interventions, methods used to measure adherence and the way the studies were reported, we did not pool the results and these findings were inappropriate to be included in a meta-analysis. Education and counselling of participants with epilepsy had mixed success (moderate-certainty evidence). Behavioural interventions such as the use of intensive reminders provided more favourable effects on adherence (moderate-certainty evidence). The effect on adherence to antiepileptic drugs described by studies of mixed interventions showed improved adherence in the intervention groups compared to the control groups (high-certainty evidence). Eleven studies described seizure frequency or seizure severity or both, with four of them, reporting improved adherence and decreased seizure frequency in the intervention groups (moderate-certainty evidence). Findings related to self-efficacy and quality of life were mixed, with no clear pattern across types of intervention.
AUTHORS' CONCLUSIONS: Behavioural interventions such as intensive reminders and the use of mixed interventions demonstrate some positive results, however, we need more reliable evidence on their efficacy, derived from carefully-designed RCTs before we can draw a firm conclusion. None of the newly included studies have provided additional information that would lead to significant changes in our conclusions.
Background: Worldwide, hormonal contraceptives are among the most popular reversible contraceptives. Despite high perfect-use effectiveness rates, typical-use effectiveness rates for shorter-term methods such as oral and injectable contraceptives are much lower. In large part, this disparity reflects difficulties in ongoing adherence to the contraceptive regimen and low continuation rates. Correct use of contraceptives to ensure effectiveness is vital to reducing unintended pregnancy. Objectives: To determine the effectiveness of strategies aiming to improve adherence to, and continuation of, shorter-term hormonal methods of contraception compared with usual family planning care. Search methods: We searched to July 2018 in the following databases (without language restrictions): The Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 7), PubMed via MEDLINE, POPLINE, Web of Science, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP). Selection criteria: We included randomized controlled trials (RCTs) comparing strategies aimed to facilitate adherence and continuation of shorter-term hormonal methods of contraception (such as oral contraceptives (OCs), injectable depot medroxyprogesterone acetate (DMPA or Depo-Provera), intravaginal ring, or transdermal patch) with usual family planning care in reproductive age women seeking to avoid pregnancy. Data collection and analysis: We used standard methodological procedures recommended by Cochrane. Primary outcomes were continuation or discontinuation of contraceptive method, rates of discontinuation due to adverse events (menstrual disturbances and all other adverse events), and adherence to method use as indicated by missed pills and on-time/late injections. Pregnancy was a secondary outcome. Main results: We included 10 RCTs involving 6242 women. Six trials provided direct in-person counseling using either multiple counseling contacts or multiple components during one visit. Four trials provided intensive reminders of appointments or next dosing, of which two provided additional educational health information as well as reminders. All trials stated 'usual care' as the comparison. The certainty of the evidence ranged from very low to moderate. Main limitations were risk of bias (associated with poor reporting of methodological detail, lack of blinding, and incomplete outcome data), inconsistency, indirectness, and imprecision. Continuation of hormonal contraceptive methods. It is uncertain whether intensive counseling improves continuation of hormonal contraceptive methods compared with usual care (OR 1.28, 95% CI 1.07 to 1.54; 2624 participants; 6 studies; I2 = 79%; very low certainty evidence). The evidence suggested: if the chance of continuation with usual care is 39%, the chance of continuation with intensive counseling would be between 41% and 50%. The overall pooled OR suggested continuation of improvement, however, when stratified by contraceptive method type, the positive results were restricted to DMPA. It is uncertain whether reminders (+/- educational information) improve continuation of hormonal contraceptive methods compared with usual care (OR 1.33, 95% CI 1.03 to 1.73; 933 participants; 2 studies; I2 = 69%; very low certainty evidence).The evidence suggested: if the chance of continuation with usual care is 52%, the chance of continuation with reminders would be between 52% and 65%. Discontinuation due to adverse events. The evidence suggested that counseling may be associated with a decreased rate of discontinuation due to adverse events compared with usual care, with a lower rate of discontinuation due to menstrual disturbances (OR 0.20, 95% CI 0.11 to 0.37; 350 participants; 1 study; low certainty evidence), but may make little or no difference to all other adverse events (OR 0.73, 95% CI 0.36 to 1.47; 350 participants; 1 study; low certainty evidence). The evidence suggested: if the chance of discontinuation with usual care due to menstrual disturbances is 32%, the chance of discontinuation with intensive counseling would be between 5% and 15%; and that if the chance of discontinuation with usual care due to other adverse events is 55%, the chance of discontinuation with intensive counseling would be between 30% and 64%. Discontinuation was not reported among trials that investigated the use of reminders (+/- educational information). Adherence. Adherence was not reported among trials that investigated the use of intensive counseling. Among trials that investigated reminders (+/- educational information), there was no conclusive evidence of a difference in adherence as indicated by missed pills (MD 0.80, 95% CI -1.22 to 2.82; 73 participants; 1 study; moderate certainty evidence) or by on-time injections (OR 0.84, 95% CI 0.54 to 1.29; 350 participants; 2 studies; I2 = 0%; low certainty evidence). The evidence suggested: if the chance of adherence to method use as indicated by on-time injections with usual care is 50%, the chance of adherence with method use as indicated by on-time injections with reminders would be between 35% and 56%. Pregnancy. There was no conclusive evidence of a difference in rates of pregnancy between intensive counseling and usual care (OR 1.24, 95% CI 0.98 to 1.57; 1985 participants; 3 studies; I2 = 0%, very low certainty evidence). The evidence suggested: if the chance of pregnancy with usual care is 18%, the chance of pregnancy with counseling would be between 18% and 25%. Pregnancy was not reported among trials that investigated the use of reminders (+/- educational information). Authors' conclusions: Despite the importance of this topic, studies have not been published since the last review in 2013 (nine studies) with only one study added in 2019 that neither changed the results nor improved the certainty of evidence. Overall, the certainty of evidence for strategies to improve adherence and continuation of contraceptives is low. Intensive counseling and reminders (with or without educational information) may be associated with improved continuation of shorter-term hormonal contraceptive methods when compared with usual family planning care. However, this should be interpreted with caution due to the low certainty of the evidence. Included trials used a variety of shorter-term hormonal contraceptive methods which may account for the high heterogeneity. It is possible that the effectiveness of strategies for improving adherence and continuation are contingent on the contraceptive method targeted. There was limited reporting of objectively measurable outcomes (e.g. electronic monitoring device) among included studies. Future trials would benefit from standardized definitions and measurements of adherence, and consistent terminology for describing interventions and comparisons. Further research requires larger studies, follow-up of at least one year, and improved reporting of trial methodology.
CONTEXTE: Les taux de vaccination chez les enfants et les adultes sont en augmentation, mais les niveaux de couverture vaccinale n'ont pas atteint les objectifs optimaux fixés. Par conséquent, des maladies évitables surviennent encore. A une époque où les calendriers vaccinaux deviennent de plus en plus complexes, où les attentes en matière de performances des soins primaires sont de plus en plus importantes et au vu des nombreuses sollicitations des intervenants en soins primaires, il est important de comprendre et de promouvoir les interventions efficaces en soins primaires pour augmenter la couverture vaccinale. Un défi commun pour les programmes de vaccination de tous les pays, consiste à appliquer une approche basée sur la population et à identifier toutes les personnes pouvant bénéficier de l'intervention, par exemple identifier les enfants qui devraient être vaccinés contre la rougeole. Cependant, grâce à la disponibilité croissante de registres de vaccination et des dossiers de santé électroniques, cette question est progressivement résolue. Un deuxième défi commun consiste à identifier les meilleures stratégies visant à promouvoir des taux de vaccination élevés. Trois types de stratégies ont été étudiés : (1) les interventions ciblant les patients, tels que les rappels aux patients ou les relances, (2) les interventions ciblant les professionnels et (3) les interventions ciblant les systèmes, telles que des réglementations scolaires. La principale stratégie d'intervention, et peut-être la mieux étudiée, implique des systèmes de rappel ou de relance des patients. Cet article est une mise à jour d'une revue précédemment publiée.
OBJECTIFS: Évaluer et comparer l'efficacité de différentes interventions de rappel et de relance des patients visant à améliorer la couverture vaccinale.
STRATÉGIE DE RECHERCHE DOCUMENTAIRE: Nous avons effectué des recherches dans CENTRAL, MEDLINE, EMBASE et CINAHL jusqu'en janvier 2017. Nous avons également effectué des recherches dans la littérature grise et dans des registres d'essais cliniques jusqu'en janvier 2017.
CRITÈRES DE SÉLECTION: Nous avons inclus les essais randomisés, les études contrôlées avant-après et les séries chronologiques interrompues évaluant les interventions de rappel ou de relance des patients concernant la vaccination chez les enfants, les adolescents et les adultes recevant des vaccinations dans n'importe quel contexte. Nous avons inclus des groupes témoin ne recevant pas d'intervention, les pratiques standard n'incluant pas de rappels ou de relance des patients, les campagnes médiatiques visant à promouvoir la vaccination, ou les campagnes de sensibilisation. Nous avons considéré éligibles les critères de jugement mesurant le fait de recevoir un vaccin, exceptées les vaccinations spécifiques destinées aux voyageurs. Nous avons exclu les patients hospitalisés durant la période d'étude.
RECUEIL ET ANALYSE DES DONNÉES: Nous avons suivi les procédures méthodologiques standard prévues par Cochrane et par le groupe Cochrane sur l'efficacité des pratiques et l'organisation des soins (EPOC). Nous présentons les résultats pour chaque étude individuelle sous la forme de taux relatifs à l'aide des risques relatifs, de différences de risques pour les essais randomisés, et de variations absolues en pourcentage pour les études contrôlées avant-après. Nous présentons les résultats combinés pour les essais randomisés en utilisant un modèle à effets aléatoires.
RÉSULTATS PRINCIPAUX: Les 75 études incluses portaient sur des enfants, des adolescents et des participants adultes et celles-ci ont été réalisées dans des contextes ambulatoires, dans la communauté, en soins primaires, et dans d'autres contextes dans 10 pays.Les interventions de rappel ou de relance des patients, incluant les interventions téléphoniques et les appels automatiques, les cartes postales, les lettres, les SMS, la combinaison d'e-mails ou d'appels téléphoniques, ou une combinaison de rappels ou de relance des patients avec des activités de promotion, améliorent de façon probable la proportion de participants vaccinés (risque relatif (RR) de 1,28, intervalle de confiance à 95 % (IC) 1,23 à 1,35 ; différence de risque de 8 %) sur la base de preuves de certitude modérée issues de 55 études incluant un total de 138 625 participants.Sur la base de preuves de haute certitude, trois types de rappels (stratégies uniques) améliorent la proportion de personnes vaccinées : les cartes postales (RR 1,18, IC à 95 % 1,08 à 1,30 ; huit études ; 27 734 participants), les SMS (RR 1,29, IC à 95 % 1,15 à 1,44 ; six études ; 7772 participants), et les appels automatiques (RR 1,17, IC à 95 % 1,03 à 1,32 ; cinq études ; 11 947 participants). Sur la base de preuves de certitude modérée, deux types de rappels (stratégies uniques) améliorent de façon probable la proportion de personnes vaccinées : les appels téléphoniques (RR 1,75, IC à 95 % 1,20 à 2,54 ; sept études ; 9120 participants) et les lettres aux patients (RR 1,29, IC à 95 % 1,21 à 1,38 ; 27 études ; 81 100 participants).Sur la base de preuves de certitude élevée, les rappels améliorent la proportion d'enfants vaccinés (RR 1,22, IC à 95 % 1,15 à 1,29 ; différence de risque de 8 % ; 23 études ; 31 099 participants) et d'adolescents vaccinés (RR 1,29, IC à 95 % 1,17 à 1,42 ; différence de risque de 7 % ; 10 études ; 30 868 participants). Les rappels améliorent de façon probable la proportion d'enfants vaccinés contre la grippe infantile (RR 1,51, IC à 95 % 1,14 à 1,99 ; différence de risque de 22 % ; cinq études ; 9265 participants) et la proportion d'adultes vaccinés contre la grippe (RR 1,29, IC à 95 % 1,17 à 1,43 ; différence de risque de 9 % ; 15 études ; 59 328 participants) sur la base de preuves de certitude modérée. Les rappels semblent améliorer la proportion d'adultes vaccinés contre le pneumocoque, le tétanos, l'hépatite B, et d'autres infections en dehors de la grippe sur la base de preuves de faible certitude, bien que l'intervalle de confiance comprenne l'absence d'effet (RR 2,08, IC à 95 % 0,91 à 4,78 ; quatre études ; 8065 participants).
CONCLUSIONS DES AUTEURS: Les systèmes de rappel et de relance des patients en soins primaires sont probablement efficaces pour améliorer la proportion de la population cible qui sera vaccinée.
BACKGROUND: The effectiveness of interventions to increase influenza vaccination uptake in people aged 60 years and older varies by country and participant characteristics. This review updates versions published in 2010 and 2014.
OBJECTIVES: To assess access, provider, system, and societal interventions to increase the uptake of influenza vaccination in people aged 60 years and older in the community.
SEARCH METHODS: We searched CENTRAL, which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE, Embase, CINAHL, and ERIC for this update, as well as WHO ICTRP and ClinicalTrials.gov for ongoing studies to 7 December 2017. We also searched the reference lists of included studies.
SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster-randomised trials of interventions to increase influenza vaccination in people aged 60 years or older in the community.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as specified by Cochrane.
MAIN RESULTS: We included three new RCTs for this update (total 61 RCTs; 1,055,337 participants). Trials involved people aged 60 years and older living in the community in high-income countries. Heterogeneity limited some meta-analyses. We assessed studies as at low risk of bias for randomisation (38%), allocation concealment (11%), blinding (44%), and selective reporting (100%). Half (51%) had missing data. We assessed the evidence as low-quality. We identified three levels of intervention intensity: low (e.g. postcards), medium (e.g. personalised phone calls), and high (e.g. home visits, facilitators).Increasing community demand (12 strategies, 41 trials, 53 study arms, 767,460 participants)One successful intervention that could be meta-analysed was client reminders or recalls by letter plus leaflet or postcard compared to reminder (odds ratio (OR) 1.11, 95% confidence interval (CI) 1.07 to 1.15; 3 studies; 64,200 participants). Successful interventions tested by single studies were patient outreach by retired teachers (OR 3.33, 95% CI 1.79 to 6.22); invitations by clinic receptionists (OR 2.72, 95% CI 1.55 to 4.76); nurses or pharmacists educating and nurses vaccinating patients (OR 152.95, 95% CI 9.39 to 2490.67); medical students counselling patients (OR 1.62, 95% CI 1.11 to 2.35); and multiple recall questionnaires (OR 1.13, 95% CI 1.03 to 1.24).Some interventions could not be meta-analysed due to significant heterogeneity: 17 studies tested simple reminders (11 with 95% CI entirely above unity); 16 tested personalised reminders (12 with 95% CI entirely above unity); two investigated customised compared to form letters (both 95% CI above unity); and four studies examined the impact of health risk appraisals (all had 95% CI above unity). One study of a lottery for free groceries was not effective.Enhancing vaccination access (6 strategies, 8 trials, 10 arms, 9353 participants)We meta-analysed results from two studies of home visits (OR 1.30, 95% CI 1.05 to 1.61) and two studies that tested free vaccine compared to patient payment for vaccine (OR 2.36, 95% CI 1.98 to 2.82). We were unable to conduct meta-analyses of two studies of home visits by nurses plus a physician care plan (both with 95% CI above unity) and two studies of free vaccine compared to no intervention (both with 95% CI above unity). One study of group visits (OR 27.2, 95% CI 1.60 to 463.3) was effective, and one study of home visits compared to safety interventions was not.Provider- or system-based interventions (11 strategies, 15 trials, 17 arms, 278,524 participants)One successful intervention that could be meta-analysed focused on payments to physicians (OR 2.22, 95% CI 1.77 to 2.77). Successful interventions tested by individual studies were: reminding physicians to vaccinate all patients (OR 2.47, 95% CI 1.53 to 3.99); posters in clinics presenting vaccination rates and encouraging competition between doctors (OR 2.03, 95% CI 1.86 to 2.22); and chart reviews and benchmarking to the rates achieved by the top 10% of physicians (OR 3.43, 95% CI 2.37 to 4.97).We were unable to meta-analyse four studies that looked at physician reminders (three studies with 95% CI above unity) and three studies of facilitator encouragement of vaccination (two studies with 95% CI above unity). Interventions that were not effective were: comparing letters on discharge from hospital to letters to general practitioners; posters plus postcards versus posters alone; educational reminders, academic detailing, and peer comparisons compared to mailed educational materials; educational outreach plus feedback to teams versus written feedback; and an intervention to increase staff vaccination rates.Interventions at the societal levelNo studies reported on societal-level interventions.Study funding sourcesStudies were funded by government health organisations (n = 33), foundations (n = 9), organisations that provided healthcare services in the studies (n = 3), and a pharmaceutical company offering free vaccines (n = 1). Fifteen studies did not report study funding sources.
AUTHORS' CONCLUSIONS: We identified interventions that demonstrated significant positive effects of low (postcards), medium (personalised phone calls), and high (home visits, facilitators) intensity that increase community demand for vaccination, enhance access, and improve provider/system response. The overall GRADE assessment of the evidence was moderate quality. Conclusions are unchanged from the 2014 review.
BACKGROUND: Lipid-lowering drugs are widely underused, despite strong evidence indicating they improve cardiovascular end points. Poor patient adherence to a medication regimen can affect the success of lipid-lowering treatment.
OBJECTIVES: To assess the effects of interventions aimed at improving adherence to lipid-lowering drugs, focusing on measures of adherence and clinical outcomes.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO and CINAHL up to 3 February 2016, and clinical trials registers (ANZCTR and ClinicalTrials.gov) up to 27 July 2016. We applied no language restrictions.
SELECTION CRITERIA: We evaluated randomised controlled trials of adherence-enhancing interventions for lipid-lowering medication in adults in an ambulatory setting with a variety of measurable outcomes, such as adherence to treatment and changes to serum lipid levels. Two teams of review authors independently selected the studies.
DATA COLLECTION AND ANALYSIS: Three review authors extracted and assessed data, following criteria outlined by the Cochrane Handbook for Systematic Reviews of Interventions. We assessed the quality of the evidence using GRADEPro.
MAIN RESULTS: For this updated review, we added 24 new studies meeting the eligibility criteria to the 11 studies from prior updates. We have therefore included 35 studies, randomising 925,171 participants. Seven studies including 11,204 individuals compared adherence rates of those in an intensification of a patient care intervention (e.g. electronic reminders, pharmacist-led interventions, healthcare professional education of patients) versus usual care over the short term (six months or less), and were pooled in a meta-analysis. Participants in the intervention group had better adherence than those receiving usual care (odds ratio (OR) 1.93, 95% confidence interval (CI) 1.29 to 2.88; 7 studies; 11,204 participants; moderate-quality evidence). A separate analysis also showed improvements in long-term adherence rates (more than six months) using intensification of care (OR 2.87, 95% CI 1.91 to 4.29; 3 studies; 663 participants; high-quality evidence). Analyses of the effect on total cholesterol and LDL-cholesterol levels also showed a positive effect of intensified interventions over both short- and long-term follow-up. Over the short term, total cholesterol decreased by a mean of 17.15 mg/dL (95% CI 1.17 to 33.14; 4 studies; 430 participants; low-quality evidence) and LDL-cholesterol decreased by a mean of 19.51 mg/dL (95% CI 8.51 to 30.51; 3 studies; 333 participants; moderate-quality evidence). Over the long term (more than six months) total cholesterol decreased by a mean of 17.57 mg/dL (95% CI 14.95 to 20.19; 2 studies; 127 participants; high-quality evidence). Included studies did not report usable data for health outcome indications, adverse effects or costs/resource use, so we could not pool these outcomes. We assessed each included study for bias using methods described in the Cochrane Handbook for Systematic Reviews of Interventions. In general, the risk of bias assessment revealed a low risk of selection bias, attrition bias, and reporting bias. There was unclear risk of bias relating to blinding for most studies.
AUTHORS' CONCLUSIONS: The evidence in our review demonstrates that intensification of patient care interventions improves short- and long-term medication adherence, as well as total cholesterol and LDL-cholesterol levels. Healthcare systems which can implement team-based intensification of patient care interventions may be successful in improving patient adherence rates to lipid-lowering medicines.
BACKGROUND: The introduction of point-of-care devices for the management of patients on oral anticoagulation allows self-testing by the patient at home. Patients who self-test can either adjust their medication according to a pre-determined dose-INR (international normalized ratio) schedule (self-management), or they can call a clinic to be told the appropriate dose adjustment (self-monitoring). Increasing evidence suggests self-testing of oral anticoagulant therapy is equal to or better than standard monitoring. This is an updated version of the original review published in 2010.
OBJECTIVES: To evaluate the effects on thrombotic events, major haemorrhages, and all-cause mortality of self-monitoring or self-management of oral anticoagulant therapy compared to standard monitoring.
SEARCH METHODS: For this review update, we re-ran the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), 2015, Issue 6, the Cochrane Library, MEDLINE (Ovid, 1946 to June week 4 2015), Embase (Ovid, 1980 to 2015 week 27) on 1 July 2015. We checked bibliographies and contacted manufacturers and authors of relevant studies. We did not apply any language restrictions .
SELECTION CRITERIA: Outcomes analysed were thromboembolic events, mortality, major haemorrhage, minor haemorrhage, tests in therapeutic range, frequency of testing, and feasibility of self-monitoring and self-management.
DATA COLLECTION AND ANALYSIS: Review authors independently extracted data and we used a fixed-effect model with the Mantzel-Haenzel method to calculate the pooled risk ratio (RR) and Peto’s method to verify the results for uncommon outcomes. We examined heterogeneity amongst studies with the Chi2 and I2 statistics and used GRADE methodology to assess the quality of evidence.
MAIN RESULTS: We identified 28 randomised trials including 8950 participants (newly incorporated in this update: 10 trials including 4227 participants). The overall quality of the evidence was generally low to moderate. Pooled estimates showed a reduction in thromboembolic events (RR 0.58, 95% CI 0.45 to 0.75; participants = 7594; studies = 18; moderate quality of evidence). Both, trials of self-management or self-monitoring showed reductions in thromboembolic events (RR 0.47, 95% CI 0.31 to 0.70; participants = 3497; studies = 11) and (RR 0.69, 95% CI 0.49 to 0.97; participants = 4097; studies = 7), respectively; the quality of evidence for both interventions was moderate. No reduction in all-cause mortality was found (RR 0.85, 95% CI 0.71 to 1.01; participants = 6358; studies = 11; moderate quality of evidence). While self-management caused a reduction in all-cause mortality (RR 0.55, 95% CI 0.36 to 0.84; participants = 3058; studies = 8); self-monitoring did not (RR 0.94, 95% CI 0.78 to 1.15; participants = 3300; studies = 3); the quality of evidence for both interventions was moderate. In 20 trials (8018 participants) self-monitoring or self-management did not reduce major haemorrhage (RR 0.95, 95% CI, 0.80 to 1.12; moderate quality of evidence). There was no significant difference found for minor haemorrhage (RR 0.97, 95% CI 0.67 to 1.41; participants = 5365; studies = 13). The quality of evidence was graded as low because of serious risk of bias and substantial heterogeneity (I2 = 82%).
AUTHORS' CONCLUSIONS: Participants who self-monitor or self-manage can improve the quality of their oral anticoagulation therapy. Thromboembolic events were reduced, for both those self-monitoring or self-managing oral anticoagulation therapy. A reduction in all-cause mortality was observed in trials of self-management but not in self-monitoring, with no effects on major haemorrhage.
BACKGROUND: Patient adherence to medications, particularly for conditions requiring prolonged treatment such as tuberculosis (TB), is frequently less than ideal and can result in poor treatment outcomes. Material incentives to reward good behaviour and enablers to remove economic barriers to accessing care are sometimes given in the form of cash, vouchers, or food to improve adherence.
OBJECTIVES: To evaluate the effects of material incentives and enablers in patients undergoing diagnostic testing, or receiving prophylactic or curative therapy, for TB.
SEARCH METHODS: We undertook a comprehensive search of the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; Science Citation Index; and reference lists of relevant publications up to 5 June 2015.
SELECTION CRITERIA: Randomized controlled trials of material incentives in patients being investigated for TB, or on treatment for latent or active TB.
DATA COLLECTION AND ANALYSIS: At least two review authors independently screened and selected studies, extracted data, and assessed the risk of bias in the included trials. We compared the effects of interventions using risk ratios (RR), and presented RRs with 95% confidence intervals (CI). The quality of the evidence was assessed using GRADE.
MAIN RESULTS: We identified 12 eligible trials. Ten were conducted in the USA.: in adolescents (one trial), in injection drug or cocaine users (four trials), in homeless adults (three trials), and in prisoners (two trials). The remaining two trials, in general adult populations, were conducted in Timor-Leste and South Africa. Sustained incentive programmesOnly two trials have assessed whether material incentives and enablers can improve long-term adherence and completion of treatment for active TB, and neither demonstrated a clear benefit (RR 1.04, 95% CI 0.97 to 1.14; two trials, 4356 participants; low quality evidence). In one trial, the incentive, given as a daily hot meal, was not well received by the population due to the inconvenience of attending the clinic at midday, whilst in the other trial, nurses distributing the vouchers chose to "ration" their distribution among eligible patients, giving only to those whom they felt were most deprived.Three trials assessed the effects of material incentives and enablers on completion of TB prophylaxis with mixed results (low quality evidence). A large effect was seen with regular cash incentives given to drug users at each clinic visit in a setting with extremely low treatment completion in the control group (treatment completion 52.8% intervention versus 3.6% control; RR 14.53, 95% CI 3.64 to 57.98; one trial, 108 participants), but no effects were seen in one trial assessing a one-off cash incentive for recently released prisoners (373 participants), or another trial assessing material incentives offered by parents to teenagers (388 participants). Single once-only incentivesHowever in specific populations, such as recently released prisoners, drug users, and the homeless, trials show that material incentives probably do improve one-off clinic re-attendance for initiation or continuation of anti-TB prophylaxis (RR 1.58, 95% CI 1.27 to 1.96; three trials, 595 participants; moderate quality evidence), and may increase the return rate for reading of tuberculin skin test results (RR 2.16, 95% CI 1.41 to 3.29; two trials, 1371 participants; low quality evidence). Comparison of different types of incentivesSingle trials in specific sub-populations suggest that an immediate cash incentive may be more effective than delaying the incentive until completion of treatment (RR 1.11, 95% CI 0.98 to 1.24; one trial, 300 participants; low quality evidence), cash incentives may be more effective than non-cash incentives (completion of TB prophylaxis: RR 1.26, 95% CI 1.02 to 1.56; one trial, 141 participants; low quality evidence; return for skin test reading: RR 1.13, 95% CI 1.07 to 1.19; one trial, 652 participants; low quality evidence); and higher cash incentives may be more effective than lower cash incentives (RR 1.08, 95% CI 1.01 to 1.16; one trial, 404 participants; low quality evidence).
AUTHORS' CONCLUSIONS: Material incentives and enablers may have some positive short term effects on clinic attendance, particularly for marginal populations such as drug users, recently released prisoners, and the homeless, but there is currently insufficient evidence to know if they can improve long term adherence to TB treatment.
BACKGROUND: Growing expenditures on prescription medicines represent a major challenge to many health systems. Cap and co-payment policies are intended as an incentive to deter unnecessary or marginal utilisation, and to reduce third-party payer expenditures by shifting parts of the financial burden from insurers to patients, thus increasing their financial responsibility for prescription medicines. Direct patient payment policies include caps (maximum numbers of prescriptions or medicines that are reimbursed), fixed co-payments (patients pay a fixed amount per prescription or medicine), co-insurance (patients pay a percentage of the price), ceilings (patients pay the full price or part of the cost up to a ceiling, after which medicines are free or are available at reduced cost) and tier co-payments (differential co-payments usually assigned to generic and brand medicines). This is the first update of the original review.
OBJECTIVES: To determine the effects of cap and co-payment (cost-sharing) policies on use of medicines, healthcare utilisation, health outcomes and costs (expenditures).
SEARCH METHODS: For this update, we searched the following databases and websites: The Cochrane Central Register of Controlled Trials (CENTRAL) (including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register, Cochrane Library; MEDLINE, Ovid; EMBASE, Ovid; IPSA, EBSCO; EconLit, ProQuest; Worldwide Political Science Abstracts, ProQuest; PAIS International, ProQuest; INRUD Bibliography; WHOLIS, WHO; LILACS), VHL; Global Health Library WHO; PubMed, NHL; SCOPUS; SciELO, BIREME; OpenGrey; JOLIS Library Network; OECD Library; World Bank e-Library; World Health Organization, WHO; World Bank Documents & Reports; International Clinical Trials Registry Platform (ICTRP), WHO; ClinicalTrials.gov, NIH. We searched all databases during January and February 2013, apart from SciELO, which we searched in January 2012, and ICTRP and ClinicalTrials.gov, which we searched in March 2014.
SELECTION CRITERIA: We defined policies in this review as laws, rules or financial or administrative orders made by governments, non-government organisations or private insurers. We included randomised controlled trials, non-randomised controlled trials, interrupted time series studies, repeated measures studies and controlled before-after studies of cap or co-payment policies for a large jurisdiction or system of care. To be included, a study had to include an objective measure of at least one of the following outcomes: medicine use, healthcare utilisation, health outcomes or costs (expenditures).
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study limitations. We reanalysed time series data for studies with sufficient data, if appropriate analyses were not reported.
MAIN RESULTS: We included 32 full-text articles (17 new) reporting evaluations of 39 different interventions (one study - Newhouse 1993 - comprises five papers). We excluded from this update eight controlled before-after studies included in the previous version of this review, because they included only one site in their intervention or control groups. Five papers evaluated caps, and six evaluated a cap with co-insurance and a ceiling. Six evaluated fixed co-payment, two evaluated tiered fixed co-payment, 10 evaluated a ceiling with fixed co-payment and 10 evaluated a ceiling with co-insurance. Only one evaluation was a randomised trial. The certainty of the evidence was found to be generally low to very low.Increasing the amount of money that people pay for medicines may reduce insurers' medicine expenditures and may reduce patients' medicine use. This may include reductions in the use of life-sustaining medicines as well as medicines that are important in treating chronic conditions and medicines for asymptomatic conditions. These types of interventions may lead to small decreases in or uncertain effects on healthcare utilisation. We found no studies that reliably reported the effects of these types of interventions on health outcomes.
AUTHORS' CONCLUSIONS: The diversity of interventions and outcomes addressed across studies and differences in settings, populations and comparisons made it difficult to summarise results across studies. Cap and co-payment polices may reduce the use of medicines and reduce medicine expenditures for health insurers. However, they may also reduce the use of life-sustaining medicines or medicines that are important in treating chronic, including symptomatic, conditions and, consequently, could increase the use of healthcare services. Fixed co-payment with a ceiling and tiered fixed co-payment may be less likely to reduce the use of essential medicines or to increase the use of healthcare services.
BACKGROUND: Tuberculosis (TB) requires at least six months of treatment. If treatment is incomplete, patients may not be cured and drug resistance may develop. Directly Observed Therapy (DOT) is a specific strategy, endorsed by the World Health Organization, to improve adherence by requiring health workers, community volunteers or family members to observe and record patients taking each dose.
OBJECTIVES: To evaluate DOT compared to self-administered therapy in people on treatment for active TB or on prophylaxis to prevent active disease. We also compared the effects of different forms of DOT.
SEARCH METHODS: We searched the following databases up to 13 January 2015: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; EMBASE; LILACS and mRCT. We also checked article reference lists and contacted relevant researchers and organizations.
SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs comparing DOT with routine self-administration of treatment or prophylaxis at home.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias of each included trial and extracted data. We compared interventions using risk ratios (RR) with 95% confidence intervals (CI). We used a random-effects model if meta-analysis was appropriate but heterogeneity present (I(2) statistic > 50%). We assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS: Eleven trials including 5662 participants met the inclusion criteria. DOT was performed by a range of people (nurses, community health workers, family members or former TB patients) in a variety of settings (clinic, the patient's home or the home of a community volunteer). DOT versus self-administered Six trials from South Africa, Thailand, Taiwan, Pakistan and Australia compared DOT with self-administered therapy for treatment. Trials included DOT at home by family members, community health workers (who were usually supervised); DOT at home by health staff; and DOT at health facilities. TB cure was low with self-administration across all studies (range 41% to 67%), and direct observation did not substantially improve this (RR 1.08, 95% CI 0.91 to 1.27; five trials, 1645 participants, moderate quality evidence). In a subgroup analysis stratified by the frequency of contact between health services in the self-treatment arm, daily DOT may improve TB cure when compared to self-administered treatment where patients in the self-administered group only visited the clinic every month (RR 1.15, 95% CI 1.06 to 1.25; two trials, 900 participants); but with contact in the control becoming more frequent, this small effect was not apparent (every two weeks: RR 0.96, 95% CI 0.83 to 1.12; one trial, 497 participants; every week: RR 0.90, 95% CI 0.68 to 1.21; two trials, 248 participants).Treatment completion showed a similar pattern, ranging from 59% to 78% in the self-treatment groups, and direct observation did not improve this (RR 1.07, 95% CI 0.96 to 1.19; six trials, 1839 participants, moderate quality evidence). DOT at home versus DOT at health facility In four trials that compared DOT at home by family members, or community health workers, with DOT by health workers at a health facility there was little or no difference in cure or treatment completion (cure: RR 1.02, 95% CI 0.88 to 1.18, four trials, 1556 participants, moderate quality evidence; treatment completion: RR 1.04, 95% CI 0.91 to 1.17, three trials, 1029 participants, moderate quality evidence). DOT by family member versus DOT by community health workerTwo trials compared DOT at home by family members with DOT at home by community health workers. There was also little or no difference in cure or treatment completion (cure: RR 1.02, 95% CI 0.86 to 1.21; two trials, 1493 participants, moderate quality evidence; completion: RR 1.05, 95% CI 0.90 to 1.22; two trials, 1493 participants, low quality evidence). Specific patient categoriesA trial of 300 intravenous drug users in the USA evaluated direct observation with no observation in TB prophylaxis to prevent active disease and showed little difference in treatment completion (RR 1.00, 95% CI 0.88 to 1.13; one trial, 300 participants, low quality evidence).
AUTHORS' CONCLUSIONS: From the existing trials, DOT did not provide a solution to poor adherence in TB treatment. Given the large resource and cost implications of DOT, policy makers might want to reconsider strategies that depend on direct observation. Other options might take into account financial and logistical barriers to care; approaches that motivate patients and staff; and defaulter follow-up.
BACKGROUND: People who are prescribed self administered medications typically take only about half their prescribed doses. Efforts to assist patients with adherence to medications might improve the benefits of prescribed medications.
OBJECTIVES: The primary objective of this review is to assess the effects of interventions intended to enhance patient adherence to prescribed medications for medical conditions, on both medication adherence and clinical outcomes.
SEARCH METHODS: We updated searches of The Cochrane Library, including CENTRAL (via http://onlinelibrary.wiley.com/cochranelibrary/search/), MEDLINE, EMBASE, PsycINFO (all via Ovid), CINAHL (via EBSCO), and Sociological Abstracts (via ProQuest) on 11 January 2013 with no language restriction. We also reviewed bibliographies in articles on patient adherence, and contacted authors of relevant original and review articles.
SELECTION CRITERIA: We included unconfounded RCTs of interventions to improve adherence with prescribed medications, measuring both medication adherence and clinical outcome, with at least 80% follow-up of each group studied and, for long-term treatments, at least six months follow-up for studies with positive findings at earlier time points.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all data and a third author resolved disagreements. The studies differed widely according to medical condition, patient population, intervention, measures of adherence, and clinical outcomes. Pooling results according to one of these characteristics still leaves highly heterogeneous groups, and we could not justify meta-analysis. Instead, we conducted a qualitative analysis with a focus on the RCTs with the lowest risk of bias for study design and the primary clinical outcome.
MAIN RESULTS: The present update included 109 new RCTs published since the previous update in January 2007, bringing the total number of RCTs to 182; we found five RCTs from the previous update to be ineligible and excluded them. Studies were heterogeneous for patients, medical problems, treatment regimens, adherence interventions, and adherence and clinical outcome measurements, and most had high risk of bias. The main changes in comparison with the previous update include that we now: 1) report a lack of convincing evidence also specifically among the studies with the lowest risk of bias; 2) do not try to classify studies according to intervention type any more, due to the large heterogeneity; 3) make our database available for collaboration on sub-analyses, in acknowledgement of the need to make collective advancement in this difficult field of research. Of all 182 RCTs, 17 had the lowest risk of bias for study design features and their primary clinical outcome, 11 from the present update and six from the previous update. The RCTs at lowest risk of bias generally involved complex interventions with multiple components, trying to overcome barriers to adherence by means of tailored ongoing support from allied health professionals such as pharmacists, who often delivered intense education, counseling (including motivational interviewing or cognitive behavioral therapy by professionals) or daily treatment support (or both), and sometimes additional support from family or peers. Only five of these RCTs reported improvements in both adherence and clinical outcomes, and no common intervention characteristics were apparent. Even the most effective interventions did not lead to large improvements in adherence or clinical outcomes.
AUTHORS' CONCLUSIONS: Across the body of evidence, effects were inconsistent from study to study, and only a minority of lowest risk of bias RCTs improved both adherence and clinical outcomes. Current methods of improving medication adherence for chronic health problems are mostly complex and not very effective, so that the full benefits of treatment cannot be realized. The research in this field needs advances, including improved design of feasible long-term interventions, objective adherence measures, and sufficient study power to detect improvements in patient-important clinical outcomes. By making our comprehensive database available for sharing we hope to contribute to achieving these advances.
Poor adherence to antiepileptic medication is associated with increased mortality, morbidity and healthcare costs. In this review, we focus on interventions designed and tested in randomised controlled trials (RCTs) and quasi-RCTs to assist people with adherence to antiepileptic medication. This is an update of a Cochrane review first published in 2011, and last updated in 2017.
OBJECTIVES:
To determine the effectiveness of interventions aimed at improving adherence to antiepileptic medication in adults and children with epilepsy.
SEARCH METHODS:
For the latest update, we searched the following databases on 18 February 2020: Cochrane Register of Studies (CRS Web), MEDLINE, CINAHL Plus and PsycINFO. CRS Web includes RCTs or quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), CENTRAL, and the Specialized Registers of Cochrane Review Groups including Epilepsy. We also searched the reference lists of relevant articles.
SELECTION CRITERIA:
RCTs and quasi-RCTs of adherence-enhancing interventions aimed at people with a clinical diagnosis of epilepsy (as defined in individual studies), of any age and treated with antiepileptic drugs in a primary care, outpatient or other community setting.
DATA COLLECTION AND ANALYSIS:
All review authors independently assessed lists of potentially relevant citations and abstracts. At least two review authors independently extracted data and performed a quality assessment of each study according to the Cochrane tool for assessing risk of bias. We graded the level of evidence for each outcome according to GRADE. The studies differed widely according to the type of intervention and measures of adherence; therefore combining data was not appropriate.
MAIN RESULTS:
We included 20 studies reporting data on 2832 participants. Thirteen studies targeted adults with epilepsy, one study included participants of all ages, one study included participants older than two years, one recruited pediatric patients aged between 1 month to 15 years, one study targeted caregivers of children with epilepsy, one targeted adolescents and caregivers, and two studies targeted families of children with epilepsy. We identified three ongoing studies. Follow-up time was generally short in most studies, ranging from 1 to 12 months. The studies examined three main types of interventions: educational interventions, behavioural interventions and mixed interventions. All but three studies compared treatment with usual care or 'no intervention'. Due to heterogeneity between studies in terms of interventions, methods used to measure adherence and the way the studies were reported, we did not pool the results and these findings were inappropriate to be included in a meta-analysis. Education and counselling of participants with epilepsy had mixed success (moderate-certainty evidence). Behavioural interventions such as the use of intensive reminders provided more favourable effects on adherence (moderate-certainty evidence). The effect on adherence to antiepileptic drugs described by studies of mixed interventions showed improved adherence in the intervention groups compared to the control groups (high-certainty evidence). Eleven studies described seizure frequency or seizure severity or both, with four of them, reporting improved adherence and decreased seizure frequency in the intervention groups (moderate-certainty evidence). Findings related to self-efficacy and quality of life were mixed, with no clear pattern across types of intervention.
AUTHORS' CONCLUSIONS:
Behavioural interventions such as intensive reminders and the use of mixed interventions demonstrate some positive results, however, we need more reliable evidence on their efficacy, derived from carefully-designed RCTs before we can draw a firm conclusion. None of the newly included studies have provided additional information that would lead to significant changes in our conclusions.
