The implementation of HTA in medicine pricing and reimbursement policies in Indonesia:Insights from multiple stakeholders

OBJECTIVES: This study aimed to identify the barriers and facilitators to improve the use of health technology assessment (HTA) for the selection of medicines listed in the e-Catalogue and the national formulary in Indonesia. METHODS: Semi-structured interviews were conducted to collect qualitative data. Purposive sampling was used to recruit the stakeholders consisting of policymakers, a pharmaceutical industry representative, healthcare providers, and patients. The data were analyzed using directed content analysis and following the COnsolidated criteria for REporting Qualitative studies (COREQ). RESULTS: The twenty-five participants interviewed agreed with the use of HTA for supporting the e-Catalogue and the national formulary and perceived the advantages of HTA implementation outweighed the disadvantages. Barriers mentioned were a lack of capability of local human resources, financial incentives, a clear framework and insufficient data. Strategies suggested to overcome the barriers were establishing (inter)national networks to build up capacity, setting up departments of HTA in several universities in Indonesia, and introducing a clear HTA framework. Facilitators mentioned were the ambition to achieve universal health coverage, the presence of legal frameworks to implement HTA in the e-Catalogue and the national formulary, and the demands for appropriate medicine policies. CONCLUSIONS: Several barriers are currently hampering broad implementation of HTA in medicine pricing and reimbursement policy in Indonesia. Solutions to these issues appear feasible and important facilitators exist

Clinical pharmacists in Dutch general practice:an integrated care model to provide optimal pharmaceutical care

Background: Medication-related harm is a major problem in healthcare. New models of integrated care are required to guarantee safe and efficient use of medication. Aim: To prevent medication-related harm by integrating a clinical pharmacist in the general practice team. This best practice paper provides an overview of 1. the development of this function and the integration process and 2. its impact, measured with quantitative and qualitative analyses. Setting: Ten general practices in the Netherlands. Development and implementation of the (pragmatic) experiment: We designed a 15-month workplace-based post-graduate learning program to train pharmacists to become clinical pharmacists integrated in general practice teams. In close collaboration with general practitioners, clinical pharmacists conduct clinical medication reviews (CMRs), hold patient consultations for medication-related problems, carry out quality improvement projects and educate the practice staff. As part of the Pharmacotherapy Optimisation through Integration of a Non-dispensing pharmacist in a primary care Team (POINT) intervention study, ten pharmacists worked full-time in general practices for 15 months and concurrently participated in the training program. Evaluation of this integrated care model included both quantitative and qualitative analyses of the training program, professional identity formation and effectiveness on medication safety. Evaluation: The integrated care model improved medication safety: less medication-related hospitalisations occurred compared to usual care (rate ratio 0.68 (95% CI: 0.57–0.82)). Essential hereto were the workplace-based training program and full integration in the GP practices: this supported the development of a new professional identity as clinical pharmacist. This new caregiver proved to align well with the general practitioner. Conclusion: A clinical pharmacist in general practice proves a feasible integrated care model to improve the quality of drug therapy

Intensive monitoring studies for assessing medicines : a systematic review

Copyright © 2019 Torre, Cary, Borges, Ferreira, Alarcão, Leufkens, Costa and Martins. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Introduction: Intensive monitoring (IM) is one of the methods of post-marketing active surveillance based upon event monitoring, which has received interest in the current medicines regulatory landscape. For a specific period of time, IM involves primary data collection and is actively focused on gathering longitudinal information, mainly safety, since the first day of drug use. Objectives: To describe IM systems and studies' data published over 11-years period (2006-2016). Specifically, we reviewed study population/event surveillance, methodological approaches, limitations, and its applications in the real-world evidence generation data. Methods: We completed a systematic search of MEDLINE and EMBASE to identify studies published from 2006 to 2016, that used IM methodology. We extracted data using a standardized form and results were analyzed descriptively. The methodological quality of selected studies was assessed using the modified Downs and Black checklist. Results: From 1,400 screened citations, we identified 86 papers, corresponding to 69 different studies. Seventy percent of reviewed studies corresponded to established IM systems, of which, more than half were prescription event monitoring (PEM) and modified-PEM. Among non-established IM systems, vaccines were the most common studied drugs (n = 14). The median cohort size ranged from 488 (hospitals) to 10,479 (PEM) patients. Patients and caregivers were the event data source in 39.1% of studies. The mean overall quality score was similar between established and non-established IM. Conclusions: Over the study period, IM studies were implemented in 26 countries with different maturity levels of post-marketing surveillance systems. We identified two major limitations: only 20% of studies were conducted at hospital-level, which is a matter of concern, insofar as healthcare systems are facing a lack of access to new medicines at ambulatory care level. Additionally, IM access to data of drug exposure cohorts, either at identification or at follow-up stages, could somehow constitute a barrier, given the complexity of managerial, linkable, and privacy data issues.The publication fee was supported by the Center for Health Evaluation and Research (CEFAR), National Association of Pharmacies, Lisbon, Portugal.info:eu-repo/semantics/publishedVersio

A novel method for predicting the budget impact of innovative medicines:validation study for oncolytics

Background High budget impact (BI) estimates of new drugs have led to decision-making challenges potentially resulting in restrictions in patient access. However, current BI predictions are rather inaccurate and short term. We therefore developed a new approach for BI prediction. Here, we describe the validation of our BI prediction approach using oncology drugs as a case study. Methods We used Dutch population-level data to estimate BI where BI is defined as list price multiplied by volume. We included drugs in the antineoplastic agents ATC category which the European Medicines Agency (EMA) considered a New Active Substance and received EMA marketing authorization (MA) between 2000 and 2017. A mixed-effects model was used for prediction and included tumor site, orphan, first in class or conditional approval designation as covariates. Data from 2000 to 2012 were the training set. BI was predicted monthly from 0 to 45 months after MA. Cross-validation was performed using a rolling forecasting origin with e|Ln(observed BI/predicted BI)| as outcome. Results The training set and validation set included 25 and 44 products, respectively. Mean error, composed of all validation outcomes, was 2.94 (median 1.57). Errors are higher with less available data and at more future predictions. Highest errors occur without any prior data. From 10 months onward, error remains constant. Conclusions The validation shows that the method can relatively accurately predict BI. For payers or policymakers, this approach can yield a valuable addition to current BI predictions due to its ease of use, independence of indications and ability to update predictions to the most recent data

Performance of a trigger tool for detecting adverse drug reactions in patients with polypharmacy acutely admitted to the geriatric ward

PURPOSE: Adverse drug reactions (ADRs) account for 10% of acute hospital admissions in older people, often under-recognised by physicians. The Dutch geriatric guideline recommends screening all acutely admitted older patients with polypharmacy with an ADR trigger tool comprising ten triggers and associated drugs frequently causing ADRs. This study investigated the performance of this tool and the recognition by usual care of ADRs detected with the tool. METHODS: A cross-sectional study was performed in patients ≥ 70 years with polypharmacy acutely admitted to the geriatric ward of the University Medical Centre Utrecht. Electronic health records (EHRs) were screened for trigger-drug combinations listed in the ADR trigger tool. Two independent appraisers assessed causal probability with the WHO-UMC algorithm and screened EHRs for recognition of ADRs by attending physicians. Performance of the tool was defined as the positive predictive value (PPV) for ADRs with a possible, probable or certain causal relation. RESULTS: In total, 941 trigger-drug combinations were present in 73% (n = 253/345) of the patients. The triggers fall, delirium, renal insufficiency and hyponatraemia covered 86% (n = 810/941) of all trigger-drug combinations. The overall PPV was 41.8% (n = 393/941), but the PPV for individual triggers was highly variable ranging from 0 to 100%. Usual care recognised the majority of ADRs (83.5%), increasing to 97.1% when restricted to possible and certain ADRs. CONCLUSION: The ADR trigger tool has predictive value; however, its implementation is unlikely to improve the detection of unrecognised ADRs in older patients acutely admitted to our geriatric ward. Future research is needed to investigate the tool's clinical value when applied to older patients acutely admitted to non-geriatric wards

Decision making under uncertainty: comparing regulatory and health technology assessment reviews of medicines in the United States and Europe

Assessments of clinical evidence vary between regulators and health technology assessment bodies, but precise differences remain unclear. To compare uncertainties raised on the clinical evidence of approved drugs, we analyzed assessments of regulators and health technology assessment (HTA) bodies in the United States and Europe. We found that US and European regulators report uncertainties related to safety for almost all drugs (85–94%), whereas HTA bodies reported these less (53–59%). By contrast, HTA bodies raised uncertainties related to effects against relevant comparators for almost all drugs (88–100%), whereas this was infrequently addressed by regulators (12–32%). Regulators as well as HTA bodies reported uncertainties related to the patient population for 60–95% of drugs. The patterns of regulator-HTA misalignment were comparable between the United States and Europe. Our results indicate that increased coordination between these complementary organizations is necessary to facilitate the collection of necessary evidence in an efficient and timely manner

A comparative human rights analysis of laws and policies for adolescent contraception in Uganda and Kenya

BACKGROUND: Improving access to adolescent contraception information and services is essential to reduce unplanned adolescent pregnancies and maternal mortality in Uganda and Kenya, and attain the SDGs on health and gender equality. This research studies to what degree national laws and policies for adolescent contraception in Uganda and Kenya are consistent with WHO standards and human rights law. METHODS: This is a comparative content analysis of law and policy documents in force between 2010 and 2018 governing adolescent (age 10–19 years) contraception. Between and within country differences were analysed using WHO’s guidelines “Ensuring human rights in the provision of contraceptive information and services”. RESULTS: Of the 93 laws and policies screened, 26 documents were included (13 policies in Uganda, 13 policies in Kenya). Ugandan policies include a median of 1 WHO recommendation for adolescent contraception per policy (range 0–4) that most frequently concerns contraception accessibility. Ugandan policies have 6/9 WHO recommendations (14/24 sub-recommendations) and miss entirely WHO’s recommendations for adolescent contraception availability, quality, and accountability. On the other hand, most Kenyan policies consistently address multiple WHO recommendations (median 2 recommendations/policy, range 0–6), most frequently for contraception availability and accessibility for adolescents. Kenyan policies cover 8/9 WHO recommendations (16/24 sub-recommendations) except for accountability. CONCLUSIONS: The current policy landscapes for adolescent contraception in Uganda and Kenya include important references to human rights and evidence-based practice (in WHO’s recommendations); however, there is still room for improvement. Aligning national laws and policies with WHO’s recommendations on contraceptive information and services for adolescents may support interventions to improve health outcomes, provided these frameworks are effectively implemented. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12978-021-01303-8

Sex disparities in the effect of statins on lipid parameters:The PharmLines Initiative

Real-world evidence on a potential statin effect modification by sex is inconclusive, especially for the primary prevention of cardiovascular disease (CVD). We aimed to quantify the differences in the effect of statins on lipid parameters between men and women. The PharmLines Initiative linked the Lifelines Cohort Study and the IADB.nl prescription database. This database covers a representative population from the Netherlands. We selected participants aged ≥40 years at the index date: the date of the first prescription of any statin monotherapy in the study period 2006 to 2017. Multivariate regression modeling was used to compare the difference of the mean percentage change of lipid parameters (% mean difference [MD]) from baseline to follow-up measurement between the sexes. Out of 5366 statin users from approximately 50,000 participants available in the final linked database, 685 were statin initiators. At baseline, women had significantly higher levels of mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) than men (all P values <.01). At follow-up, women had a significantly higher mean percentage change of HDL-C compared to men (adjusted % MD 5.59, 95% confidence interval [CI] 2.42-8.75, P < .01). There was no significant sex difference in other parameters, nor in the proportion of men and women who achieved LDL-C ≤2.5 mmol/L. Statins appear to have a greater effect on increasing HDL-C levels in women than men while showing similar effect on other lipid parameters in both sexes. Men should not be treated differently than women

Prescribing Errors With Low-Molecular-Weight Heparins

BACKGROUND: Low-molecular-weight heparins (LMWHs) are used in the prevention and treatment of venous thromboembolism (VTE). Bleeding is the primary major complication of LMWH therapy, which is associated with dose. The administration of appropriate dosages of LMWHs depends on the patient's risk of VTE, risk of bleeding, bodyweight, and renal function. Therefore, LMWH prescribing is prone to errors. However, no earlier study has explored the frequency of prescribing errors with LMWH. PURPOSE: The aim of the study was to determine the frequency and determinants of in-hospital LMWH-prescribing errors. METHODS: A cross-sectional study was conducted to examine the frequency and determinants of LMWH prescribing errors between April and August 2014. We randomly selected 500 patients 18 years and older with at least one LMWH prescription during inpatient hospitalization. A prescribing error was a deviation from the internal hospital guidelines. Logistic regression estimated determinants of prescribing error. RESULTS: A prescribing error was present with 34% of all LMWH users. The most frequently recorded error was a dose that was not adjusted to body weight and/or renal function (85%). Prophylactic LMWH prescribing in medical wards was associated with a higher risk of prescribing error as compared with surgical wards. CONCLUSIONS: The frequency of prescribing errors was 34% in a tertiary care hospital. Being a patient with prophylactic LMWH use on a medical ward is a determinant for LMWH prescribing error. Interventions that will lead to better electronic recording of body weight and more awareness among medical doctors may reduce the total number of prescribing errors

Barriers and Enablers of Older Patients to Deprescribing of Cardiometabolic Medication:A Focus Group Study

Background Deprescribing has been recommended for managing polypharmacy but deprescribing preventive medication in older patients is still uncommon. We aimed to investigate older patients' barriers to and enablers of deprescribing cardiometabolic medication. Methods Two focus groups were conducted among patients >= 70 years with polypharmacy, including cardiometabolic medication. Purposive sampling through four community pharmacies was used in two regions in the Netherlands. A topic list was developed using literature and the theoretical domains framework (TDF). The meetings were audio recorded, transcribed verbatim and coded using thematic coding, attribute coding and the TDF. In addition, patients were categorized on attitudes towards medication and willingness to stop. Results The meetings were attended by 17 patients and 1 caregiver (71 to 84 years). In total 15 barriers and 13 enablers were identified within four themes, partly related to beliefs, fears and experiences regarding using or stopping medication, and partly related to the relationship with the health care professional and the conditions to stop. Some patients attributed their wellbeing to their medication and were therefore unwilling to stop. Reducing cardiometabolic medication because of less strict treatment targets confused some patients and was a barrier to deprescribing. Having options to monitor clinical measurements and restart medication were enablers. Patients were only willing to stop cardiometabolic medication when this was proposed by a HCP they trusted. Patients with a positive attitude towards medication varied in their willingness to stop cardiometabolic medication. Patients with a negative attitude towards medication were generally willing to stop medication but still perceived several barriers and may consider some medication as being essential. Conclusion Fears, beliefs, and experiences regarding using and stopping medication as well as trust in the HCP influence willingness to have medication deprescribed. Attitudes towards medication in general do not necessarily translate into willingness or unwillingness to stop specific medication. For deprescribing cardiometabolic medication, patient involvement when setting new treatment targets and monitoring the effects on short-term outcomes are important