Effectiveness and cost-effectiveness of an intervention to improve Initial Medication Adherence to treatments for cardiovascular diseases and diabetes in primary care: study protocol for a pragmatic cluster randomised controlled trial and economic model (the IMA-cRCT study).

BACKGROUND: Between 2 and 43% of patients who receive a new prescription in PC do not initiate their treatments. Non-initiation is associated with poorer clinical outcomes, more sick leave and higher costs to the healthcare system. Existing evidence suggests that shared decision-making positively impacts medication initiation. The IMA-cRCT assesses the effectiveness of the IMA intervention in improving adherence and clinical parameters compared to usual care in patients with a new treatment for cardiovascular disease and diabetes prescribed in PC, and its cost-effectiveness, through a cRCT and economic modelling. METHODS: The IMA intervention is a shared decision-making intervention based on the Theoretical Model of Non-initiation. A cRCT will be conducted in 24 PC teams in Catalonia (Spain), randomly assigned to the intervention group (1:1), and community pharmacies in the catchment areas of the intervention PC teams. Healthcare professionals in the intervention group will apply the intervention to all patients who receive a new prescription for cardiovascular disease or diabetes treatment (no other prescription from the same pharmacological group in the previous 6 months). All the study variables will be collected from real-world databases for the 12 months before and after receiving a new prescription. Effectiveness analyses will assess impact on initiation, secondary adherence, cardiovascular risk, clinical parameters and cardiovascular events. Cost-effectiveness analyses will be conducted as part of the cRCT from a healthcare and societal perspective in terms of extra cost per cardiovascular risk reduction and improved adherence; all analyses will be clustered. Economic models will be built to assess the long-term cost-effectiveness of the IMA intervention, in terms of extra cost for gains in QALY and life expectancy, using clinical trial data and data from previous studies. DISCUSSION: The IMA-cRCT represents an innovative approach to the design and evaluation of behavioural interventions that use the principles of complex interventions, pragmatic trials and implementation research. This study will provide evidence on the IMA intervention and on a new methodology for developing and evaluating complex interventions. The results of the study will be disseminated among stakeholders to facilitate its transferability to clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05026775 . Registered 30th August 2021.

Who Suffers From Pharmaceutical Poverty and What Are Their Needs? Evidence From a Spanish Region.

Background: Pharmaceutical poverty occurs when a patient cannot afford the cost of prescribed medication and/or medical products. Nonprofit organizations are covering the cost of medication to those patients in some contexts. The aim of the study was to describe the population of beneficiaries of the PB, a nongovernmental organization based on the primary healthcare system, which provides free-of-charge access to medicines and their utilization pattern of medicines and healthcare products. Methods: This was an observational study using PB beneficiary data collected between November 2017 and December 2018 in Catalonia. The Catalan Health Service provided information from the general population. A descriptive analysis of the beneficiaries' characteristics was conducted and compared to the general population. Results: The beneficiaries (N = 1,206) were mainly adults with a low level of education, unemployed, with functional disability, and with ≥1 child. Compared with the general population, the beneficiaries were older, had a lower level of education, showed a higher prevalence of functional disability, were less likely to be Spanish, and were more likely to be divorced and unemployed. The beneficiaries were polymedicated, and most were using medication related to the nervous (79%), musculoskeletal (68%), and cardiovascular system (56%) and alimentary tract and metabolism (68%). Almost 19% of beneficiaries used healthcare products. Female beneficiaries were older and more likely to be divorced or widowed, employed, and with children. Compared to men, women were more likely to use medicines for pain and mental disorders. The pediatric group used medications for severe, chronic conditions (heart diseases, autoimmune diseases, conduct disorders, and attention deficit hyperactivity disorder). Conclusion: Patients with severe, chronic, and disabling conditions are affected by pharmaceutical poverty. While the system of copayment remains unchanged, family physicians and pediatricians should explore economic barriers to treatment and direct their patients to resources that help to cover the cost of treatment.

Diagnostic accuracy and treatment approach to depression in primary care: predictive factors.

Objective: The study assessed the predictive factors of diagnostic accuracy and treatment approach (antidepressants versus active monitoring) for depression in primary care. Methods: This is a cross-sectional study that uses information from a naturalistic prospective controlled trial performed in Barcelona (Spain) enrolling newly diagnosed patients with mild to moderate depression by GPs. Treatment approach was based on clinical judgement. Diagnosis was later assessed according to DSM-IV criteria using Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) interview by an external researcher. Patients (sociodemographic, psychiatric diagnosis, severity of depression and anxiety, health-related quality of life, disability, beliefs about medication and illness and comorbidities) and GP factors associated with diagnostic accuracy and treatment approach were assessed using multilevel logistic regression. Variables with missing data were imputed through multiple imputations. Results: Two hundred sixty-three patients were recruited by 53 GPs. Mean age was 51 years (SD = 15). Thirty percent met DSM-IV criteria for major depression. Mean depression symptomatology was moderate-severe. Using multivariate analyses, patients' beliefs about medicines were the only variable associated with the antidepressant approach. Specialization in general medicine and being a resident tutor were associated with a more accurate diagnosis. Conclusions: Clinical depression diagnosis by GPs was not always associated with a formal diagnosis through a SCID-I. GPs' training background was central to an adequate depression diagnosis. Patients' beliefs in medication were the only factor associated with treatment approach. More resources should be allocated to improving the diagnosis of depression.

Comparing watchful waiting with antidepressants for the management of subclinical depression symptoms to mild-moderate depression in primary care: a systematic review.

Background: The benefits of watchful waiting (WW) over antidepressants (ADs) for the treatment of depression in primary care (PC) are unclear. Objective: We aimed to systematically review the evidence supporting either WW or ADs for the treatment of subclinical depressive symptoms and mild-moderate depression in a PC setting. Methods: This systematic review was registered at PROSPERO (42016036345). Four electronic sources (EMBASE, PubMed, PsycINFO, Web of Knowledge) were systematically searched from inception to November 2016 for controlled trials comparing WW and ADs in PC following established guidelines. The studies had to include adult population with new symptoms of subclinical depression or mild-moderate depression. Patients in the intervention group should receive a WW approach, while patients in the control group underwent treatment with ADs. The abstraction form included information on the setting, characteristics of the study population, total sample size, size of the control and intervention groups and date of the study. Outcome measures and variability were extracted. Results: The scarcity of studies and the considerable clinical and methodological heterogeneity discouraged us from performing a meta-analysis. Three articles were included and qualitatively synthesized. There was no evidence for the superiority of one treatment option over the other, although two of the studies suggested small differences in favour of ADs when less conservative analyses were conducted (per protocol analysis and analysis not adjusted for missingness predictors). Conclusions: Superiority was not demonstrated by either treatment option. More robust evidence is needed to inform recommendations for the management of depressive symptoms in PC.

Impact of IPDE-SQ personality disorders on the healthcare and societal costs of fibromyalgia patients: a cross-sectional study.

BACKGROUND: Data is lacking on comorbid personality disorders (PD) and fibromyalgia syndrome (FMS) in terms of prevalence, and associated healthcare and societal costs. The main aim of this study was to assess the prevalence of PD in FMS patients and to analyse whether the presence of comorbid PD is related to worse functional impairment and greater healthcare (medical visits, drug consumption, and medical tests) and societal costs. METHODS: A cross-sectional study was performed using the baseline data of 216 FMS patients participating in a randomized, controlled trial carried out in three primary health care centres situated in the region of Barcelona, Spain. Measurement instruments included the International Personality Disorder Examination - Screening Questionnaire (IPDE-SQ), the Fibromyalgia Impact Questionnaire (FIQ), the Client Service Receipt Inventory (CSRI), and a socio-demographic questionnaire. RESULTS: Most patients (65 %) had a potential PD according to the IPDE-SQ. The most prevalent PD were the avoidant (41.4 %), obsessive-compulsive (33.1 %), and borderline (27 %). We found statistically significant differences in functional impairment (FIQ scores) between FMS patients with potential PD vs non-PD (59.2 vs 51.1; p < 0.001). Multivariate regression analyses revealed that higher FIQ total scores and the presence of potential PD were related to more healthcare costs (primary and specialised care visits). CONCLUSIONS: As expected, PD are frequent comorbid conditions in patients with FMS. Our results suggest that the screening of comorbid PD in patients with FMS might be recommendable in order to detect potential frequent attenders to primary and specialised care.

Impacto de una intervención farmacéutica en la prevención de recaídas en depresión en atención primaria / Impact of pharmaceutical intervention in preventing relapses in depression in Primary Care

OBJETIVO: Evaluar el impacto a largo plazo de una intervención farmacéutica (IF) respecto a la atención habitual (AH) en la prevención de recaídas en depresión. DISEÑO: Ensayo clínico aleatorizado (estudio PRODEFAR). Emplazamiento: Atención primaria. PARTICIPANTES: Ciento setenta y nueve pacientes con depresión mayor que inician antidepresivos, de estos, se seleccionaron para este análisis secundario los 113 cuyos síntomas habían remitido (definición principal) a los 6 meses (grupo intervención [GI] = 58; grupo control [GC] = 55). Intervención: Se realizó una entrevista personal en la farmacia comunitaria para mejorar la adhesión terapéutica durante la dispensación de medicación. MEDICIONES PRINCIPALES: Se realizaron 3 mediciones (línea base, 3 y 6 meses). La gravedad de síntomas depresivos (PHQ-9) fue evaluada a los 6 meses y se seleccionaron aquellos pacientes que presentaban remisión. Se revisaron sus historias clínicas para identificar recaídas, mediante 4 indicadores, en los siguientes 12 meses. RESULTADOS: La proporción de recaídas (variable principal) fue menor en el GI respecto al GC a los 18 meses de haber iniciado el tratamiento, pero la diferencia no fue estadísticamente significativa, ni en análisis por intención de tratar (OR = 0,734 [IC 95% 0,273;1,975]) ni en el análisis por protocolo (OR = 0,615 [95% CI 0,183; 2,060]). Todos los análisis de sensibilidad mostraron resultados consistentes. El tamaño de la muestra y la adhesión al protocolo en el GI fueron bajos. CONCLUSIÓN: El GI mostró una tendencia no significativa a presentar un menor número de recaídas. Esto podría relacionarse con la mejora en la adhesión entre los pacientes que recibieron la IF

OBJECTIVE: To evaluate the long-term impact of a brief pharmacist intervention (PI) compared with usual care (UC) on prevention of depression relapse. DESIGN: randomised controlled clinical trial SETTING: Primary Care. PARTICIPANTS: Of the 179 depressed patients initiating antidepressants, the 113 whose clinical symptoms had remitted (main definition) at 6 months assessment were selected for this secondary study (PI = 58; UC = 55). Intervention: PI was an interview to promote medication adherence when patients get antidepressants from pharmacy. MAIN MEASUREMENTS: Baseline, 3 months, and six-months follow-up assessments were made. The severity of depressive symptoms was evaluated with PHQ9. Patients presenting a remission of symptoms were selected. The patient medical records were reviewed to identify a relapse in the following 12 months by using 4 indicators. RESULTS: There was a lower proportion of patients that relapsed in the PI group than in the UC group 18 months after initiation of treatment, but the difference was not statistically significant either in the intent-to-treat analysis (OR = 0.734 [95%CI; 0.273-1.975]) or the per-protocol analysis (OR = 0.615 [95%CI; 0.183 -2.060]). All the sensitivity analyses showed consistent results. The sample size and adherence to the protocol in the intervention group were low. CONCLUSION: PI group showed a non-statistically significant tendency towards presenting fewer relapses. This could be related to the improvement in adherence among patients that received the intervention

[Impact of pharmaceutical intervention in preventing relapses in depression in Primary Care]. / Impacto de una intervención farmacéutica en la prevención de recaídas en depresión en atención primaria.

OBJECTIVE: To evaluate the long-term impact of a brief pharmacist intervention (PI) compared with usual care (UC) on prevention of depression relapse. DESIGN: randomised controlled clinical trial SETTING: Primary Care PARTICIPANTS: Of the 179 depressed patients initiating antidepressants, the 113 whose clinical symptoms had remitted (main definition) at 6 months assessment were selected for this secondary study (PI=58; UC=55). INTERVENTION: PI was an interview to promote medication adherence when patients get antidepressants from pharmacy. MAIN MEASUREMENTS: Baseline, 3 months, and six-months follow-up assessments were made. The severity of depressive symptoms was evaluated with PHQ9. Patients presenting a remission of symptoms were selected. The patient medical records were reviewed to identify a relapse in the following 12 months by using 4 indicators. RESULTS: There was a lower proportion of patients that relapsed in the PI group than in the UC group 18 months after initiation of treatment, but the difference was not statistically significant either in the intent-to-treat analysis (OR=0.734 [95%CI; 0.273-1.975]) or the per-protocol analysis (OR=0.615 [95%CI; 0.183 -2.060]). All the sensitivity analyses showed consistent results. The sample size and adherence to the protocol in the intervention group were low. CONCLUSION: PI group showed a non-statistically significant tendency towards presenting fewer relapses. This could be related to the improvement in adherence among patients that received the intervention.

Evaluation of a pharmacist intervention on patients initiating pharmacological treatment for depression: a randomized controlled superiority trial.

Major depression is associated with high burden, disability and costs. Non-adherence limits the effectiveness of antidepressants. Community pharmacists (CP) are in a privileged position to help patients cope with antidepressant treatment. The aim of the study was to evaluate the impact of a CP intervention on primary care patients who had initiated antidepressant treatment. Newly diagnosed primary care patients were randomised to usual care (UC) (92) or pharmacist intervention (87). Patients were followed up at 6 months and evaluated three times (Baseline, and at 3 and 6 months). Outcome measurements included clinical severity of depression (PHQ-9), health-related quality of life (HRQOL) (Euroqol-5D) and satisfaction with pharmacy care. Adherence was continuously registered from the computerised pharmacy records. Non-adherence was defined as refilling less than 80% of doses or having a medication-free gap of more than 1 month. Patients in the intervention group were more likely to remain adherent at 3 and 6 months follow-up but the difference was not statistically significant. Patients in the intervention group showed greater statistically significant improvement in HRQOL compared with UC patients both in the main analysis and PP analyses. No statistically significant differences were observed in clinical symptoms or satisfaction with the pharmacy service. The results of our study indicate that a brief intervention in community pharmacies does not improve depressed patients' adherence or clinical symptoms. This intervention helped patients to improve their HRQOL, which is an overall measure of patient status.

Community pharmacist intervention in depressed primary care patients (PRODEFAR study): randomized controlled trial protocol.

BACKGROUND: Treatment of depression, the most prevalent and costly mental disorder, needs to be improved. Non-concordance with clinical guidelines and non-adherence can limit the efficacy of pharmacological treatment of depression. Through pharmaceutical care, pharmacists can improve patients' compliance and wellbeing. The aim of this study is to evaluate the effectiveness and cost-effectiveness of a community pharmacist intervention developed to improve adherence and outcomes of primary care patients with depression. METHODS/DESIGN: A randomized controlled trial, with 6-month follow-up, comparing patients receiving a pharmaceutical care support programme in primary care with patients receiving usual care. The total sample comprises 194 patients (aged between 18 and 75) diagnosed with depressive disorder in a primary care health centre in the province of Barcelona (Spain). Subjects will be asked for written informed consent in order to participate in the study. Diagnosis will be confirmed using the SCID-I. The intervention consists of an educational programme focused on improving knowledge about medication, making patients aware of the importance of compliance, reducing stigma, reassuring patients about side-effects and stressing the importance of carrying out general practitioners' advice. Measurements will take place at baseline, and after 3 and 6 months. Main outcome measure is compliance with antidepressants. Secondary outcomes include; clinical severity of depression (PHQ-9), anxiety (STAI-S), health-related quality of life (EuroQol-5D), satisfaction with the treatment received, side-effects, chronic physical conditions and socio-demographics. The use of healthcare and social care services will be assessed with an adapted version of the Client Service Receipt Inventory (CSRI). DISCUSSION: This trial will provide valuable information for health professionals and policy makers on the effectiveness and cost-effectiveness of a pharmaceutical intervention programme in the context of primary care. TRIAL REGISTRATION: NCT00794196.