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Background Chronic migraine is a disabling condition, affecting 2–4% of adults globally. With the introduction of expensive calcitonin gene-related peptide monoclonal antibodies, it is timely to compare the clinical effectiveness and cost-effectiveness of preventive drugs for chronic migraine. Objective To assess the clinical effectiveness and cost-effectiveness of medications used for chronic migraine through systematic reviews and economic modelling. Eligibility criteria Randomised controlled trials of drug treatments for efficacy with > 100 participants with chronic migraine per arm; for adverse events > 100 participants with episodic or chronic migraine per arm. Previous economic analyses of preventive drugs for chronic migraine. Data sources Eight databases. Reviews methods Systematic reviews, network meta-analysis and economic modelling. Outcomes Monthly headache days, monthly migraine days, headache-related quality of life, cost-effectiveness. Results We found 51 individual articles, reporting 11 randomised controlled trials, testing 6 drugs (topiramate, Botox, eptinezumab, erenumab, fremanezumab, galcanezumab), versus placebo, on 7352 adults with chronic migraine. Calcitonin gene-related peptide monoclonal antibodies, Botox and topiramate reduced headache/migraine days by 2.0–2.5, just under two, or by less than 1.5 days per month, respectively. In the network meta-analysis, eptinezumab 300 mg and fremanezumab monthly ranked in first place in both monthly headache day and monthly migraine day analyses. The calcitonin gene-related peptide monoclonal antibodies were consistently the best choices for headache/migraine days and headache-related quality of life. Topiramate was very unlikely to be the best choice for headache/migraine days and headache-related quality of life when compared to calcitonin gene-related peptide monoclonal antibodies or Botox. We found no trials of the commonly used drugs, such as propranolol or amitriptyline, to include in the analysis. The adverse events review included 40 randomised controlled trials with 25,891 participants; 3 additional drugs, amitriptyline, atogepant and rimegepant, were included. There were very few serious adverse events – none of which were linked to the use of these medications. Adverse events were common. Most people using some calcitonin gene-related peptide monoclonal antibodies reported injection site issues; and people using topiramate or amitriptyline had nervous system or gastrointestinal issues. The cost-effectiveness review identified 16 studies evaluating chronic migraine medications in adults. The newer, injected drugs are more costly than the oral preventatives, but they were cost-effective. Our economic model showed that topiramate was the least costly option and had the fewest quality-adjusted life-year gains, whereas eptinezumab 300 mg was more costly but generated the most quality-adjusted life-year gains. The cost-effectiveness acceptability frontier showed that topiramate was the most cost-effective medication if the decision maker is willing to pay up to £50,000 per quality-adjusted life-year. Our consensus workshop brought together people with chronic migraine and headache experts. Consensus was reached on the top three recommendations for future research on medications to prevent chronic migraine: (1) calcitonin gene-related peptide monoclonal antibodies and Botox versus calcitonin gene-related peptide monoclonal antibodies, (2) candesartan versus placebo and (3) flunarizine versus placebo. Limitations Topiramate was the only oral drug for which we were able to include data. We did not find sufficient quality evidence to support the use of other oral drugs. Conclusions We did not find evidence that the calcitonin gene-related peptide monoclonal antibodies are more clinically and cost-effective when compared to topiramate or Botox. We identified directions for future research these drugs might take. Study registration This study is registered as PROSPERO CRD42021265990, CRD42021265993 and CRD42021265995. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR132803) and is published in full in Health Technology Assessment; Vol. 28, No. 63. See the NIHR Funding and Awards website for further award information. Plain language summary What is the problem? Chronic migraine is a disabling condition that can destroy work and family life. Treatments include cheap tablets (e.g. amitriptyline, propranolol and topiramate), Botox and expensive new drugs (the calcitonin gene-related peptide monoclonal antibodies). It is not known which of these drugs is the best choice. What did we want to find out? We wanted to find out which of these drugs works best. We wanted to know if they reduced the number of headache/migraine days and improved headache-related quality of life, how many side effects people experienced, and if they provided good value for the National Health Service. How did we do this? We first looked for research comparing these drugs to placebo (fake) drugs, and to each other. We then worked out which provide best value for money. What did we find out? Calcitonin gene-related peptide monoclonal antibodies reduced headache/migraine days by 2.0–2.5 days per month; Botox reduced headache/migraine days per month by around 1.9; and topiramate reduced headache/migraine days by 1.1–1.5 days per month. Many people taking topiramate or amitriptyline have nervous system and/or stomach/bowel side effects. Some people using calcitonin gene-related peptide monoclonal antibodies reported side effects associated with injections. Some calcitonin gene-related peptide monoclonal antibodies and Botox provide worthwhile benefits on headache-related quality of life. We were not able to identify any studies of sufficient quality to assess the effectiveness of other oral drugs. The best value drug was topiramate which gave better health outcomes at a lower cost than the placebos. What does this mean? After sharing the results with a panel of people with chronic migraine and headache experts, we identified a need for new studies comparing commonly used cheap oral drugs with placebo, Botox and calcitonin gene-related peptide monoclonal antibodies. Scientific summary Background Chronic migraine is a profoundly disabling condition and affects 2–4% of the world’s adult population. It is defined as headaches on 15 days or more a month with features of migraine on at least 8 of those days. Since 2020, expensive calcitonin gene-related peptide (CGRP) monoclonal antibodies (MAbs) have become established as specific treatments for people with chronic migraine who have failed to improve with other medications. Little is known about the effectiveness of these drugs when compared with each other, or with other well-established, cheaper, oral drugs used to treat chronic migraine. Therefore, it is timely to compare the clinical effectiveness and cost-effectiveness of these medications to treat chronic migraine. We set out to address the following research question: What is the clinical effectiveness and cost-effectiveness of prophylactic drug treatments for people with chronic migraine? Objectives Our overall aim is to produce evidence needed for people with chronic migraines and their doctors to make more informed decisions about prophylactic medications for chronic migraine. Our objectives were: What is the comparative effectiveness of prophylactic drugs for chronic migraine? What are the comparative incidences of adverse events (AEs) of prophylactic drugs used for migraine? What is known about the cost-effectiveness of prophylactic drugs for chronic migraine? Which prophylactic drugs for the management of chronic migraine are the most cost-effective? Based on our findings, what should the research recommendations be? Methods Systematic reviews of trial evidence on: The clinical effectiveness of prophylactic medications for chronic migraine; analyses included headache days, migraine days and headache-related quality of life: migraine- specific quality of life (MSQ); headache impact test-6 (HIT-6). Only randomised controlled trials (RCTs) with at least 100 people per arm were included. We report the comparative effectiveness using a network meta-analysis (NMA) for these different outcomes to see which drug was the most ‘effective’. To identify the comparative incidence of AEs of prophylactic drugs used for chronic or episodic migraine. RCTs with at least 100 people per arm were included. The cost-effectiveness studies of prophylactic drugs used for treatment of chronic migraine. We developed an economic model comparing the cost-effectiveness of prophylactic drugs for chronic migraine for the adult population from a National Health Service (NHS) and personal social services (PSS) perspective. The base-case analysis used a 2-year time horizon, with a starting age of 30 years for the patient cohort. Health states in the model were based on effectiveness data [reduction in the mean difference (MD) in monthly headache days (MHDs)] from the NMA. Costs are in 2021–2 prices and utilities were estimated based on EuroQol-5 Dimensions, five-level version (EQ-5D-5L) scores from the CHESS trial using the Hernandez-Alava crosswalk algorithm. Cost-effectiveness was measured in terms of an incremental cost per quality-adjusted life-year (QALY) gained [Institute for Clinical and Economic Review (ICER)]. Probabilistic sensitivity analysis (PSA) was undertaken to account for uncertainty in model parameters. Uncertainty around the cost-effectiveness of the various medications showing which is the preferred strategy is presented using a cost-effectiveness acceptability frontier (CEAF). At the end of the project, we held a consensus workshop bringing together people with chronic migraine and clinicians and other health professionals who are experts in chronic migraine. We presented the findings from our reviews, NMA, the economic model and some potential recommendations. We then split into groups (mixed with health professionals and participants) and asked them to discuss our suggested research recommendations, identify any other recommendations, and rank these recommendations in terms of priority. We then had another breakaway session, where all participants with chronic migraine met and all health professionals met. Finally, everyone was bought back together to discuss their rankings as a wider group and to reach a consensus using anonymous polling. Results The clinical effectiveness review focused on prophylactic medications which might be used in the UK for the prevention of chronic migraine. We found 11 RCTs reported across 51 individual publications, involving 7352 adult participants with chronic migraine, which showed that all pharmacological treatments for all outcomes of interest were beneficial in preventing migraine when compared to placebo. There were no trials of sufficient quality of the commonly used drugs, such as amitriptyline, candesartan, flunarizine or propranolol. Overall, the CGRP MAbs reduced headache/migraine days by 2.0 to 2.5 days per month. The most effective medication in reducing MHDs was eptinezumab 300 mg which reduced MHDs by 2.46 [95% credible interval (CrI) 3.24 to −1.67] days. The most effective medication in reducing monthly migraine days (MMDs) was fremanezumab monthly which reduced MMDs by 2.76 (95% CrI −3.36 to −2.15) days. Botox (BTA) reduced MHDs by 1.87 (95% CrI −2.55 to −1.18) days per month and MMDs by 1.96 (95% CrI −2.69 to −1.24) days per month. Topiramate was the least effective, prescribable drug and only reduced headache/migraine days by less than 1.5 fewer headache/migraine days per month. The NMA results showed that eptinezumab 300 mg had the highest probability ranking to reduce MHDs and MMDs – Surface Under the Cumulative Ranking Area (SUCRA) was 0.88 and 0.77, respectively. The CGRP MAbs provided a worthwhile improvement on the HIT-6 measure of headache-related quality of life (eptinezumab 300 mg reducing the HIT-6 by a score of 3.22 points); BTA had a worthwhile effect on the HIT-6 measure, reducing the HIT-6 score by 2.10 points; and there was no convincing benefit of topiramate on the MSQ measure. Galcanezumab 120 mg provided the best improvement in quality of life for the preventative role dimension of migraine-specific quality of life (MSQ-PR) (MD 6.97, 95% CrI 3.79 to 10.24, SUCRA 0.88), but for two other dimensions of the MSQ, erenumab 140 mg was superior to other treatments: for migraine-specific quality of life-restrictive role (MSQ-RR) – MD: 7.28, 95% CrI: 3.05 to 11.65, SUCRA 0.75, and for migraine- specific quality of life-emotional function (MSQ-EF) – MD: 8.89, 95% CrI: 3.20 to 14.55, SUCRA 0.79. The results from the quality assessment using the revised Cochrane risk-of-bias (RoB 2) tool for RCTs found that approximately 46% of the included RCTs in this review had low RoB and 36% of the RCTs had some concerns of bias. The incidence of AEs and serious adverse events (SAEs) review used evidence from 40 RCTs reported across 67 articles, which investigated pharmacological interventions to manage chronic or episodic migraine. These trials included 25,891 participants and 3 additional drugs were included – amitriptyline, atogepant and rimegepant. There were very few SAEs – none of which were linked to the use of these drugs. Non-SAEs were common, and results suggested that all the pharmacological medications included in this review were found to be tolerable. There were differences in the incidence of AEs between the CGRP MAbs, with most people using fremanezumab and one in four people using galcanezumab reporting injection site issues. These issues were much less common in people using eptinezumab or erenumab. Most people using topiramate or amitriptyline had nervous system or gastrointestinal side effects; topiramate was also linked to a higher prevalence of psychiatric disorders; and AEs related to BTA were uncommon. The cost-effectiveness review identified nine peer-reviewed journal articles and seven published reports of chronic migraine prophylactic medications in the adult population. All articles were model-based evaluations, and none were trial-based economic evaluations. We found that although these newer drugs (BTA and CGRP MAbs) were more costly than the oral preventatives, they were however deemed cost-effective. Generally, the articles were classed as high quality when appraised by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) reporting tool. We developed a Markov (state-transition) model to assess the cost-effectiveness of different pharmacological medications to treat or prevent chronic migraine in the adult population. Our base-case deterministic results showed when comparing each of the medications separately against placebo, topiramate dominated placebo (cheaper and more effective); and each of the other medications, when compared separately, were more expensive than placebo; however, they generated more QALYs than placebo. The best value medication when compared with placebo was BTA, with the cost per QALY around £25,000. When comparing all medications together, the deterministic results showed that topiramate was the least costly option and had slightly more QALY gains than placebo, whereas eptinezumab 300 mg was the more costly option but generated the most QALY gains. Most medications were eliminated due to dominance. The ICER between BTA and topiramate and the ICER between eptinezumab 300 mg and BTA were not within plausible cost-effectiveness thresholds. Probabilistic results were similar to deterministic results. The CEAF showed that when comparing all medications topiramate was the most cost-effective medication if the decision maker is willing to pay up to £50,000 per QALY. None of the CGRP MAbs represented good value for money in this comparative analysis. Extensive sensitivity analyses showed that when MHDs is used as an outcome measure, the results were generally in line with the base-case results. The main exception was when using MMDs as an outcome measure instead of MHDs, fremanezumab monthly generated more QALY gains than eptinezumab 300 mg; the ICERs between the plausible options, once any dominated options were removed, were not within plausible cost-effectiveness thresholds. Our consensus workshop brought together 8 participants with chronic migraine and 11 health professionals with expertise in chronic migraine to set research priorities for preventive drugs for chronic migraine. Each of the small groups found that the need for trials of cheaper, oral medications, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors (SNRIs) when compared with placebo were ranked highly; and for trials comparing the medications with each other, the CGRP MAbs and BTA separately or in combination with each other were ranked highly. The final (anonymised) rankings showed that the top three research priorities versus placebo were: (1) candesartan, (2) flunarizine and (3) melatonin; and for medications compared with each other were: (1) CGRP MAbs and BTA versus CGRP MAbs, (2) CGRP MAbs versus BTA and (3) a multi-arm trial of CGRPs MAbs receptor (erenumab) versus CGRP MAbs ligand (eptinezumab, fremanezumab and galcanezumab). In terms of priority, a consensus was established regarding the three most recommended medication comparisons for treating chronic migraine: (1) CGRP MAbs and BTA versus CGRP MAbs, (2) candesartan compared to placebo and (3) flunarizine in comparison to placebo. Discussion and conclusions Of the treatments included in the NMA, the CGRP MAbs overall were consistently the best choices for headache days, migraine days and headache-related quality of life. BTA was less likely than CGRP MAbs to be the best choice for headache days, migraine days and headache-related quality of life. Topiramate was very unlikely to be the best choice for headache days, migraine days and headache-related quality of life when compared to CGRP MAbs or BTA. The economic model found that topiramate was the best value drug if you are prepared to pay up to £50,000 per QALY. It is likely that CGRP MAbs are likely to be cost-effective in people who have failed treatment with BTA. At the workshop, general consensus was agreed on the top three choices of medication for chronic migraine. Topiramate was the only established oral drug for which we were able to include data. It is disappointing that we did not find a sufficient quality evidence base to support the use of drugs, such as amitriptyline, candesartan, flunarizine and propranolol that are recommended by National Institute for Health and Care Excellence (NICE) and/or Scottish Intercollegiate Guidelines Network (SIGN). Our consensus meeting identified the need for trials comparing candesartan and flunarizine with placebo as the top priorities for placebo-controlled trials. Only for topiramate can we make any observations for how this may compare with CGRP MAbs. The CGRP MAbs appear to be clinically superior, but even so topiramate, in spite of its high incidence of AEs, represents the best value for money. Within the current care pathway, it is unlikely that CGRP MAbs will be recommended ahead of topiramate without a very substantial reduction on price. What is perhaps a more critical decision point is whether BTA or CGRP MAbs might be preferred as the first choice after failure of oral medication. Our findings support continuing with the current care pathway since our CEAF found that only topiramate met an acceptable threshold. Data from our health economics review, however, do support the use of CGRP MAbs after failure of BTA for chronic migraine. Our consensus group identified the direct comparison of BTA and CGRP MAbs as a key research question. They also identified the question of whether these drug effects might be additive. The effect sizes, in terms of mean monthly migraine/headache days for each of these drugs, are at best modest, the largest being 2.76 days for fremanezumab monthly dose. As these drugs work through different pathways, it might be that more substantial effects are possible. Adding together the effects of BTA and a CGRP MAb, assuming no negative interaction, might have a mean effect size of 4–5 days that would be transformative for many people with chronic migraine. Our consensus group identified the comparative, and additive, effects of BTA and CGRP MAbs as high priority research questions. In conclusion, we have summarised the existing clinical and cost-effectiveness data on preventive drugs for chronic migraine and identified which directions future research on these drugs might take. We did not find convincing evidence that the CGRP MAbs are more clinically effective and cost-effective compared to topiramate or BTA. Study registration This study is registered as PROSPERO CRD42021265990, CRD42021265993 and CRD42021265995. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR132803) and is published in full in Health Technology Assessment; Vol. 28, No. 63. See the NIHR Funding and Awards website for further award information.

Abstract Objective To develop an early economics evaluation (EEE) to assess the cost‐effectiveness of the GS in reducing the RoF and FoF. Methods A cost‐effectiveness analysis (CEA) with a return on investment (RoI) estimation was performed. CEA used the most relevant parameters, such as increased gait speed and decreased FoF, to estimate the reduction in the RoF, the impact on health care resources used and financial implications for the National Health System in the United Kingdom. Outcomes were measured as incremental cost‐effectiveness ratio per quality‐adjusted life years (QALYs) gained based on the reduction of the RoF and FoF. Uncertainties around the main parameters used were evaluated by probabilistic sensitivity analysis. Results The CEA results showed that the GS is a dominant strategy over the standard of care to improve the movements of older persons who have suffered a fall or are afraid of falling (incremental QALYs based on FoF = 0.77 and QALYs based on RoF = 1.07, cost of FoF = ‐£4479.57 and cost of RoF = ‐£2901.79). By implementing the GS, the ROI results suggest that every pound invested in the GS could result in cost savings of £1.85/patient based on the RoF reduction and £11.16/patient based on the FoF reduction. The probability of being cost saving based on the number of iterations were 79.4 percent (based on FoF) and 100 percent (based on RoF). Conclusion The EEE supports the main hypothesis that the GS is an effective intervention to avoid falls and is potentially cost saving.

Background: GaitSmart (GS) is a sensor-based digital medical device that can be used with the integrated app vGym to provide a personalised rehabilitation programme for older people undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). This study aimed to determine whether the GS intervention used in the rehabilitation of older people undergoing THA or TKA is potentially cost-effective compared to the current standard of care (SoC). Methods: Decision-analytic modelling was conducted to estimate the cost-effectiveness over a seventeen-week time horizon from an NHS perspective. UK clinical and cost data from the GaitSmart randomised clinical trial was used to obtain the input parameters, and a sensitivity analysis was performed to address uncertainties. Results: Over a seventeen-week time horizon, GS incurred cost savings of GBP 450.56 and a 0.02 gain in quality-adjusted life years (QALYs) compared to the SoC. These results indicate that GS is the dominant intervention because the device demonstrated greater effectiveness and lower costs. Probabilistic sensitivity analyses confirm the robustness of our results. Conclusions: GS appears to offer short-term efficiency benefits and demonstrates cost-effectiveness for the improvement in gait in people undergoing THA or TKA, compared to the SoC.

During the COVID-19 pandemic, the term “behavioural fatigue” became the centre of policy debates in Great Britain. These debates involved deciding when to go into lockdown and whether behavioural interventions could be effective. Behavioural interventions can only succeed where people’s Capabilities, Opportunities, and Motivations to perform target behaviours are supported. Our retrospective data analyses examine the relationships between people’s Capabilities, Opportunities, Motivations, and Behaviours, i.e., adherence to lockdown guidelines. Our cross-sectional analyses include 17,962 unique participants in Great Britain who completed a survey over the initial 30 days of the first lockdown (April 2020). We examine trends in responses to each scale and then the relationships between the scales using Granger’s causality test with tests for stationarity and cointegration. A mixture of increasing and decreasing trends was identified for Capabilities and Opportunities. Decreasing trends were identified for Motivation and Behaviour. Granger’s causality tests found that Capability forecasts Opportunity and Behaviour and that Motivation forecasts Opportunity. The discussion reiterates that to realise and maintain Behaviour changes, policies surrounding people’s Capabilities, Opportunities, and Motivations must continue to support target behaviours.

Abstract Background Chronic migraine (CM) is a significant neurological condition affecting a substantial portion of the global population. The economic burden of CM includes both direct healthcare costs and indirect costs resulting from productivity losses and intangible impacts on patients’ quality of life. However, there is limited research that comprehensively evaluates all cost components associated with CM, highlighting the need for a systematic review. Methods We conducted a systematic literature search in databases including MEDLINE, Embase, and CINAHL to identify studies estimating the cost of illness of chronic migraines. The search was restricted to English language articles published from inception to October 2021, and only findings from Organisation for Economic Co-operation and Development (OECD) countries were included. Methodology features and key findings were extracted from the studies, and reported costs were converted to GBP for cross-country comparisons. Results Thirteen cost-of-illness studies on CM from various OECD countries were included in this review. The studies demonstrated substantial variations in monetary estimates, but consistently highlighted the considerable economic burden of CM. Direct costs, particularly hospitalisation and medication expenses, were identified as the highest contributors. However, indirect costs, such as productivity losses due to absenteeism and presenteeism, were often underexplored in the reviewed studies. Additionally, intangible costs related to emotional and social impacts on patients were largely overlooked. Conclusion Chronic migraine imposes a significant economic burden on individuals, healthcare systems, and society. Policymakers and healthcare stakeholders should consider both direct and indirect cost components, as well as intangible costs, in developing targeted strategies for effective CM management and resource allocation. Further research focusing on comprehensive cost assessments and sensitivity analyses is needed to enhance the understanding of CM’s economic implications and inform evidence-based healthcare policy decisions. Addressing these research gaps can alleviate the economic burden of CM and improve patient outcomes.

Ensuring access to essential medicines remains a formidable challenge in Nepal. The specific reasons for the shortage of essential medicines within Nepal have not been extensively investigated. This study addresses challenges associated with access to essential medicines, procurement process difficulties, and functionality of inventory management systems at different levels of public health facilities. Fifty-nine semi-structured in-depth interviews were conducted with health managers and service providers at provincial and local levels in six randomly selected districts of Bagmati province, Nepal. Interviews were audiotaped and transcribed verbatim, and the results were analyzed using the inductive approach and were later mapped within the four domains of "Procurement of essential medicines". The major barriers for the effective management of essential medicines included delays in the procurement process, primarily locally, leading to frequent stock-out of essential drugs, particularly at the health post level. Additionally, challenges arise from storage problems, mainly due to insufficient storage space and the need to manage additional comorbidities related to COVID-19. Other identified challenges encompass the absence of training on logistics management information systems, a lack of information technology resources in primary health facilities, inadequate qualified human resources to operate the IT system, and insufficient power backup. Moreover, unrealistic demand estimation from the service points, inadequate transportation costs, and manual inventory management systems further contributed to the complex landscape of challenges. This study identified procurement delays as the primary cause of essential medicine shortages in Bagmati Province, Nepal. We recommend implementing comprehensive procurement guidelines, collaborative training, and dedicated budgets to address this issue. Improving the procurement and inventory management process in low-resource settings requires a well-trained workforce, suitable storage spaces, and enhanced coordinated administrative tiers within health facilities at different levels to ensure the year-round availability of essential medicines in these settings.

Abstract Background and aims Chronic migraine is a common neurovascular brain disorder with substantial economic costs. We performed a systematic review to identify economic evaluations of pharmacological treatments for adults with chronic migraine. Methods We undertook systematic literature searches using terms for migraine/headache and prophylactic drug interventions, combined with economic/cost terms where appropriate. Using inclusion and exclusion criteria, two reviewers independently assessed the citations and abstracts, and full-text articles were retrieved. A review of study characteristics and methodological quality was assessed. Results Sixteen citations met the inclusion criteria and were model-based cost-utility studies evaluating: Botox (n = 6); Erenumab (n = 8); Fremanezumab (n = 2); and Galcanezumab (n = 1) as the main treatment. They varied in their use of comparators, perspective, and model type. Botox was cost-effective compared to placebo with an incremental cost-effectiveness ratio (ICER) ranging between £15,028 (€17,720) and £16,598 (€19,572). Erenumab, Fremanezumab and Galcanezumab when compared to Botox, was associated with ICERs ranging between £59,712 ($81,080) and £182,128 (€218,870), with the ICERs above the most common willingness-to-pay thresholds (WTPs). But they were cost-effective within the commonly used WTPs among the population for whom the previous treatments including Botox were failed. Three studies compared the cost-effectiveness of Erenumab against the placebo and found that Erenumab was dominant. All studies performed sensitivity analyses to check the robustness of their results. None of the findings from the included articles were generalisable and none of the included studies fulfilled all the criteria mentioned in the CHEERS 2022 reporting checklist and Phillips’s checklist for economic models. Conclusions Evidence to support the cost-effectiveness of pharmacological treatments of chronic migraine in the adult population using Botox and Erenumab were identified. Our findings suggest that both Botox and Erenumab, are cost-effective compared to placebo; although Erenumab had more incremental economic benefits compared to Botox, the ICERs were above the most common willingness-to-pay thresholds. Hence, Erenumab might be an acceptable treatment for chronic migraine for patients whom other treatments such as Botox do not work. Further research is needed to help characterise the data to adequately structure and parameterise an economic model to support decision-making for chronic migraine therapies.

Background: Evidence has shown the positive impact of pharmacist involvement on the adherence and health outcomes of people living with HIV/AIDS. However, whether such intervention provides value for money remains unclear. This study aims to fill this gap by assessing the cost–effectiveness of pharmacist interventions in HIV care in Pakistan. Methods: A Markov decision analytic model was constructed, considering clinical inputs, utility data, and cost data obtained from a randomized controlled trial and an HIV cohort of Pakistani origin. The analysis was conducted from a healthcare perspective, and the incremental cost–effectiveness ratio (ICER) was calculated and presented for the year 2023. Additionally, a series of sensitivity analyses were performed to assess the robustness of the results. Results: Pharmacist intervention resulted in higher quality-adjusted life years (4.05 vs. 2.93) and likewise higher annual intervention costs than usual care (1979 USD vs. 429 USD) (532,894 PKR vs. 115,518 PKR). This yielded the ICER of 1383 USD/quality-adjusted life years (QALY) (372,406 PKR/QALY), which is well below the willingness-to-pay threshold of 1658 USD (446,456 PKR/QALY) recommended by the World Health Organization Choosing Interventions that are Cost-Effective. Probabilistic sensitivity analysis reported that more than 68% of iterations were below the lower limit of threshold. Sensitivity analysis reported intervention cost is the most important parameter influencing the ICER the most. Conclusion: The study suggests that involving pharmacists in HIV care could be a cost-effective approach. These findings could help shape healthcare policies and plans, possibly making pharmacist interventions a regular part of care for people with HIV in Pakistan.

Background Pharmacists in high-income countries routinely provide efficient pharmacy or pharmaceutical care services that are known to improve clinical, economic, and humanistic outcomes (ECHO) of patients. However, pharmacy services in low- and middle-income countries, mainly South Asia, are still evolving and limited to providing traditional pharmacy services such as dispensing prescription medicines. This systematic review aims to assess and evaluate the impact of pharmacists’ services on the ECHO of patients in South Asian countries. Methods We searched PubMed/Medline, Scopus, EMBASE, CINAHL, and Cochrane Library for relevant articles published from inception to 20th September 2021. Original studies (only randomised controlled trials) conducted in South Asian countries (published only in the English language) and investigating the economic, clinical (therapeutic and medication safety), and humanistic impact (health-related quality of life) of pharmacists’ services, from both hospital and community settings, were included. Results The electronic search yielded 430 studies, of which 20 relevant ones were included in this review. Most studies were conducted in India (9/20), followed by Pakistan (6/20), Nepal (4/20) and Sri Lanka (1/20). One study showed a low risk of bias (RoB), 12 studies showed some concern, and seven studies showed a high RoB. Follow-up duration ranged from 2 to 36 months. Therapeutic outcomes such as HbA1c value and blood pressure (systolic blood pressure and diastolic blood pressure) studied in fourteen studies were found to be reduced. Seventeen studies reported humanistic outcomes such as medication adherence, knowledge and health-related quality of life, which were found to be improved. One study reported safety and economic outcomes each. Most interventions delivered by the pharmacists were related to education and counselling of patients including disease monitoring, treatment optimisation, medication adherence, diet, nutrition, and lifestyle. Conclusion This systematic review suggests that pharmacists have essential roles in improving patients’ ECHO in South Asian countries via patient education and counselling; however, further rigorous studies with appropriate study design with proper randomisation of intervention and control groups are anticipated.

Abstract Background The quality of life (QoL) of patients with lung cancer (LC) may be affected by disease-related limitations such as patients’ functioning, the severity of symptoms, financial problems resulting along with the side effects of the treatment. The objective of this study was to translate LC-specific QoL questionnaire EORTC QLQ-LC29 into Nepalese language for Nepalese LC patients. Methods In the process of translation, the European Organization for Research and Treatment of Cancer (EORTC) translations guidelines were followed. The translated questionnaire was pilot-tested in a sample of 15 patients with LC. Descriptive statistics were calculated with SPSS version 21.0. Results All steps of the EORTC translation guideline were followed successfully. Fifteen lung cancer patients were included in the pilot study. Sixty percent were male and the mean age was 49.87 (range 21–76 years). For all items not related to thoracic surgery, patients used the entire range of the response options from 1 to 4 and no missing responses were observed. The highest mean (indicating a high symptom burden) was observed for the item number. 35 (shortness of breath; Mean = 3.33, SD = 1.11) and the lowest mean for an item number. 45 (dizzy; Mean = 1.73, SD = 0.96). Conclusion The Nepalese version of EORTC QLQ-LC29 is a result of a successfully conducted rigorous translation procedure, and is highly comprehensible as well as acceptable to Nepalese LC patients. Thus, the Nepalese version of EORTC QLQ-LC29 is ready to be used in international clinical studies as well as in Nepalese clinical practice.

Background: The benefits of medication optimization are largely uncontroversial but difficult to achieve. Behavior change interventions aiming to optimize prescriber medication-related decisions, which do not forbid any option and that do not significantly change financial incentives, offer a promising way forward. These interventions are often referred to as nudges.Objective: The current systematic literature review characterizes published studies describing nudge interventions to optimize medication prescribing by the behavioral determinants they intend to influence and the techniques they apply.Methods: Four databases were searched (MEDLINE, Embase, PsychINFO, and CINAHL) to identify studies with nudge-type interventions aiming to optimize prescribing decisions. To describe the behavioral determinants that interventionists aimed to influence, data were extracted according to the Theoretical Domains Framework (TDF). To describe intervention techniques applied, data were extracted according to the Behavior Change Techniques (BCT) Taxonomy version 1 and MINDSPACE. Next, the recommended TDF-BCT mappings were used to appraise whether each intervention applied a sufficient array of techniques to influence all identified behavioral determinants.Results: The current review located 15 studies comprised of 20 interventions. Of the 20 interventions, 16 interventions (80%) were effective. The behavior change techniques most often applied involved prompts (n = 13). The MINDSPACE contextual influencer most often applied involved defaults (n = 10). According to the recommended TDF-BCT mappings, only two interventions applied a sufficient array of behavior change techniques to address the behavioral determinants the interventionists aimed to influence.Conclusion: The fact that so many interventions successfully changed prescriber behavior encourages the development of future behavior change interventions to optimize prescribing without mandates or financial incentives. The current review encourages interventionists to understand the behavioral determinants they are trying to affect, before the selection and application of techniques to change prescribing behaviors.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020168006].

Background The COVID-19 pandemic has further strengthened the need for pharmacists to uptake non-traditional roles. Pharmacy practice in Saudi Arabia is emerging in recent years with greater policy emphasis on pharmacists taking new clinical roles. This study aimed to explore the experiences, perceptions and barriers of Saudi pharmacists about their uptake of non-traditional roles using Theoretical Domains Framework (TDF). Methods A qualitative semi-structured study using face-to-face or telephone interviews were conducted. Eligible participants included qualified pharmacists from Saudi Arabia. Interviews focused on pharmacist’s perceptions, current opportunities and key challenges towards the uptake of non-traditional roles. Interviews were audiotaped and transcribed verbatim. Results were analysed through the framework analysis method and were later mapped with respective domains of TDF. Results A total of 14 pharmacists completed the interview (9 females and 5 males). Participants showed an overall positive attitude towards the uptake of non-traditional roles. Participants felt that there was wider support available for pharmacists at the policy level to uptake non-traditional roles. However, a need for greater recognition of roles by other healthcare professionals and patients were identified. Participants alluded to reluctance of some physicians to take on board the suggestions from a pharmacist. Key barriers to uptake of non-traditional roles were related to environmental context and resources domain of TDF. For example, participants discussed the need for even further practical experiences during their undergraduate degree to become ready to adopt non-traditional roles in clinical practice. Conclusions Participants of this theoretically informed qualitative study showed an overall positive attitude towards the way pharmacy practice is progressing in Saudi Arabia and their uptake of non-traditional roles. However, there is a need to improve interdisciplinary working, patient awareness of pharmacist competencies and their educational preparedness in furthering their uptake of non-traditional roles. Addressing such barriers and promoting uptake of novel roles by pharmacists is imperative in the context of emerging COVID-19 and future pandemics.

Background The COVID-19 pandemic has disproportionately affected all essential healthcare services delivery in low-resource settings. This study aimed to explore the challenges and experiences of providers and users of childhood immunisation services in Nepal during the COVID-19 pandemic. Methods Semi-structured qualitative interviews were conducted with childhood immunisation service providers and users (i.e., parents of children) from Kathmandu valley, Nepal. All interviews were conducted through phone or internet-based tools, such as Zoom, WhatsApp, and messenger. All interviews were audio-recorded, transcribed verbatim, and analysed using theme-based content analysis in an Excel spreadsheet. Results A total of 15 participants (n = 7 service providers and n = 8 service users) participated. Six themes were identified, namely: (1) impact of COVID-19 and lockdown on childhood immunisation services; (2) motivation and resilience for childhood immunisation; (3) Biosafety practices and Personal Protective Equipment (PPE) availability during the COVID-19 pandemic; (4) service adjustments and guidelines during pandemic; (5) availability of vaccines; and (6) immunisation program resilience in view of COVID-19. Service providers mentioned facing disruptions in services and some parents had decided to delay scheduled immunisation. However, most service providers showed determinations to deliver the services with high morale, while most service users reported taking their children for immunisation. Families migrating from urban to rural areas during the pandemic led to service providers having no means to confirm complete immunisation of migrating children. Service providers also experienced lack of adequate guidance to deal with the pandemic and personal protective equipment to protect themselves and service users. Conclusion Despite experiencing disruptions in childhood immunisation service due to the COVID-19 pandemic, service users and providers were determined to vaccinate the children. There is an urgent need for effective preparedness plans to be in place to address the observed barriers and to ensure resilient immunisation services during ongoing and future pandemics.

Background: Epidemiological studies focused on primary healthcare needs of persons experiencing homelessness (PEH) are often based on data from specialist homeless healthcare services. Aim: To explore the presentation of PEH, coding of homelessness, and associated health conditions in mainstream primary care general practices in England. Design & setting: EMIS electronic database search of medical records was conducted across 48 general practices in a clinical commissioning group (CCG), representing one of the most socioeconomically deprived regions in England, which also lacks a specialist primary healthcare service for PEH. Method: Key terms and codes were used to identify PEH, their respective diagnoses across 22 health conditions, and prescribed medications over the past 4 years. Results: From a population of approximately 321 000, 43 (0.013%) people were coded as PEH, compared with a homelessness prevalence of 0.5% in the English general population. Mental health conditions were the most prevalent diagnoses among the PEH registrants (56.6%); the recorded prevalence of other common long-term conditions in PEH was lower than the levels observed in PEH registered with specialist homelessness health services. Conclusion: In a population with approximately four times higher rate of statutory homelessness, PEH representation in mainstream general practices was under-represented by several folds. As homelessness overlaps with mental health, substance misuse, and long-term health conditions, consistent coding of homelessness in medical records is imperative in order to offer tailored support and prevention actions when patients present for services.

Abstract The aim of this study was to address the problems associated with polypharmacy in elderly cancer patients and to highlight the role of pharmacists in such cases in resource‐limited settings. A narrative review of existing literature was performed to summarize the evidence regarding the impact of polypharmacy in elderly cancer patients and the pharmaceutical strategies to manage it. This review emphasizes the significance of polypharmacy, which is often ignored in real clinical practice. Polypharmacy in the elderly cancer population is mainly due to: chemotherapy with one or more neoplastic agents for cancer treatment, treatment for adverse drug reactions due to neoplastic agents, the patient's comorbid conditions, or drug interactions. The role of the clinical pharmacist in specialized oncology hospitals or oncology departments of tertiary care hospitals is well established; however, this is not the case in many developing countries. A clinical pharmacist can contribute to solving the problems associated with polypharmacy by identifying the risks associated with polypharmacy and its management in resource‐limited settings. As in many developed countries, the involvement of a clinical pharmacist in cancer care for elderly patients may play a vital role in the recognition and management of polypharmacy‐related problems. Further research can be conducted to support this role.

Pharmacists are essential members of the healthcare team. The emergence of the novel coronavirus disease 2019 (COVID-19) pandemic has led pharmacists to undertake additional clinical roles. We aim to conduct a systematic review on the interventions and impact of pharmacist-delivered services in managing COVID-19 patients. We searched PubMed, Embase, Scopus, CINAHL plus, International Pharmaceutical Abstracts, and Web of Science from 1 December 2019 (the first case of COVID-19 emerged) to 13 January 2022 to retrieve the articles. Cochrane handbook and PRISMA guidelines were followed respectively to perform and report the review. The pharmacist-led interventions were reported following the Descriptive Elements of Pharmacist Intervention Characterization Tool (DEPICT) version 2. The protocol of systematic review was registered on PROSPERO (CRD42021277128). Studies quality was assessed with the modified NOS scale. In total, 7 observational studies were identified from 10,838 studies. Identification of dosage errors (n = 6 studies), regimen modifications (n = 5), removal of obsolete/duplicate medications (n = 5), identification and management of adverse drug reactions (n = 4), drug interactions prevention (n = 2), and physicians acceptance rate (n = 3) of therapy-related services delivered in-person or via tele-pharmacy were among the pharmacist-delivered services. Common interventions delivered by pharmacists also included optimizing the use of antibacterial, antivirals, and anticoagulants in COVID-19 infected patients. The acceptance of pharmacist-delivered services by physicians was high (88.5–95.5%). Included studies have described pharmacists’ beneficial role in managing patients with COVID-19 including detection, resolution, and prevention of medication-related problems, with physicians demonstrating high trust in pharmacists’ advice. Future research should assess the feasibility and scalability of such roles in real-world settings.

Providing healthcare workers with cost information about the medications they prescribe can influence their decisions. The current study aimed to analyse the impact of two nudges that presented cost information to prescribers through a hospital’s electronic prescribing system. The nudges were co-created by the research team: four behavioural scientists and the lead hospital pharmacist. The nudges were rolled out sequentially. The first nudge provided simple cost information (percentage cost-difference between two brands of mesalazine: Asacol® and Octasa®). The second nudge provided information about the potential annual cost savings if the cheaper medication were selected across the National Health Service. Neither nudge influenced prescribing. Prescribing of Asacol® and Octasa® at baseline and during the implementation of the first nudge did not differ (at p ≥ 0.05), nor was there a difference between the first nudge and second (at p ≥ 0.05). Although these nudges were not effective, notable administrative barriers were overcome, which may inform future research. For example, although for legal reasons the cost of medicine cannot be displayed, we were able to present aggregated cost information to the prescribers. Future research could reveal more behavioural factors that facilitate medication optimisation.

Background: Sildenafil and tadalafil are recommended firstline treatments for erectile dysfunction (ED). Sildenafil was legally reclassified to a ‘pharmacy’ medicine in the UK in 2018. Aim: To assess the prescribing patterns and costs associated with prescribing of ED drugs in England, and to investigate the link between prescribing and deprivation, regional demography, and legal reclassification. Design & setting: Analyses were conducted of publicly available government data from various sources pertaining to primary care prescribing and demographics in England. Method: Prescribing and cost data from January 2009 to November 2019 were extracted and adjusted for inflation, male populations, and regional deprivation. Results: Between 2009 and 2019 the rate of prescribing, measured as the number of items per 1000 men, increased by 110%. In 2019, the rate of prescribing of ED medicines in the most deprived areas was 21.0% higher than the rate observed in least deprived areas. The northern regions of England approximately had a 50% higher rate of prescribing compared with London. A 1.3% annual increase in the number of prescription items was observed between 2018 and 2019 for Sildenafil, with a 5.8% increase observed from 2017–2018. Conclusion: The two-fold increase in the rate of primary care prescriptions in the past 10 years suggests that more men are being screened for, or seeking help for, ED. The higher rate of prescribing offers opportunity for monitoring of linked risk factors, such as diabetes mellitus, dyslipidaemia, and vascular disorders, in deprived populations. Reclassification of sildenafil had a modest impact on prescribing practices.

BackgroundUnderstanding patient satisfaction with pharmacy services can help to enhance the quality and monitoring of pharmacy services. Patient Satisfaction with Pharmacist Services Questionnaire 2.0 (PSPSQ 2.0) is a valid and reliable instrument for measuring patient satisfaction with services from the pharmacist. The availability of the PSPSQ 2.0 in Nepalese version would facilitate patient satisfaction and enhance pharmacy services in Nepal. This study aims to translate the PSPSQ 2.0 into the Nepalese version, culturally adapt it and verify its reliability and validity in the Nepalese population.MethodsThe methodological and cross-sectional study design was used to translate, culturally adapt it, and validate PSPSQ 2.0 in Nepalese. The Nepalese version of PSPSQ 2.0 went through the full linguistic validation process and was evaluated in 300 patients visiting different community pharmacies in Kathmandu district, Nepal. Exploratory factor analysis was carried out using principal component analysis with varimax rotation, and Cronbach's alpha was used to evaluate the reliability.ResultsThree-hundred patients were recruited in this study. Participants ranged in age from 21 to 83 years; mean age was 53.93 years (SD: 15.21). 62% were females, and 34% educational level was above 12 and university level. Only 7% of the participants were illiterate. Kaiser-Meyer-Olkinwas found to be 0.696, and Bartlett's test of sphericity was significant with a chi-square test value of 3695.415. A principal axis factor analysis conducted on the 20 items with orthogonal rotation (varimax). PSPSQ 2.0 Nepalese version (20 items) had a good internal consistency (Cronbach's alpha = 0.758). Item-total correlations were reviewed for the items in each of the three domains of PSPSQ 2.0.ConclusionThe PSPSQ 2.0 Nepalese version demonstrated acceptable validity and reliability, which can be used in the Nepalese population for evaluating the satisfaction of patients with pharmacist services in both community pharmacy and research.

The aim of this study was to evaluate the availability, price, and affordability of essential noncommunicable disease (NCD) medicines in Nepal. A cross-sectional survey was conducted in Nepal in 2015 using World Health Organization/Health Action International (WHO/HAI) methodology. We collected data on the availability and price of 60 essential NCD medicines from medicine distribution outlets in both the public and private health care sectors in 6 regions. Essential NCD medicines were more available in the private sector (78%) than the public sector (60%). Furosemide tablets were the cheapest (NPR 0.6/10 tablets) and streptokinase injections were the most expensive (NPR 2200/vial) drugs. There was no significant difference ( P > .05) in availability and affordability of essential NCD medicines across the 6 survey areas. Treating selected NCD conditions with medicines was generally affordable, with 1 month of treatment costing no more than a day’s wage of the lowest paid unskilled government worker. The lower availability of NCD medicines in the public sector limits the effectiveness of the government’s policy of providing free health services at public facilities. Although NCD medicines were generally affordable, future health policy should aim to ensure improved equitable access to NCD medicines, particularly in public facilities.

Abstract Background Capacity development of health volunteers and text messaging to pregnant women through mobile phones have shown improved maternal and child health (MCH) outcomes and is associated with increased utilisation of MCH services. However, such interventions are uncommon in Nepal. We aim to carry out an intervention with the hypothesis that capacity building and text messaging intervention will increase the MCH service utilisation. Method/design MATRI-SUMAN is a 12-month cluster randomized controlled trial (RCT). The trial involves pregnant women from 52 clusters of six village development committees (VDCs) covering 66,000 populations of Dhanusha district of Nepal. In the intervention clusters, Female Community Health Volunteers (FCHVs) will receive capacity development skills through reinforcement training, supervision and monitoring skills for the promotion of health seeking behaviour among pregnant women and study participants will receive periodic promotional text messaging service about MCH components through mobile phones. A sample of 354with equal numbers in each study arm is estimated using power calculation formula. The primary outcomes of this study are the rate of utilization of skilled birth attendants and consumption of a specified diversified meal. The secondary outcomes are: four antenatal (ANC) visits, weight gain of women during pregnancy, delivery of a baby at the health facility, postnatal care (PNC) visits, positive changes in child feeding practices among mothers, performance of FCHVs in MCH service utilization. Discussion The intervention is designed to enhance the capacity of health volunteers for the promotion of health seeking behaviour among pregnant women and text messaging through a mobile phone to expecting mothers to increase MCH service utilization. The trial if proven effective will have policy implications in poor resource settings. Trial registration ISRCTN60684155, (https://doi.org/10.1186/ISRCTN60684155). The trial was registered retrospectively.

Introduction: An ever-increasing trend in the use of social media offers a potential forum for exchanging information in developing countries. Easy access, quick dissemination and widespread use necessitate the incorporation of social media in adverse drug reactions reporting and pharmacovigilance activities. Aim: To highlight the potential role of the use of social media in pharmacovigilance activities in a developing country like Nepal. Materials and Methods: A review of all relevant literature was conducted from scholargoogle and PubMed databases using the search terms ‘Social media’, ‘Pharmacovigilance’, ‘Nepal’, ‘drug safety’, ‘social network’ and ‘adverse drug reaction’. In addition, a general search was conducted in Google search engine using similar terminologies. The identified literature was reviewed by the authors and the most relevant ones within the scope of the topic were included. Results: Social media use is common; the number of social media users is on increasing trend even in developing countries like Nepal. There are some unique scopes of social media in pharmacovigilance, including improving awareness, reporting and signal detection. In resource-limited settings, social media can play a crucial role in disseminating drug safety and related information. Incorporating social media in pharmacovigilance has challenges, particularly the problem associated with the authenticity and validity of information available in social media platform. Conclusion: Social media may have an opportunity in the pharmacovigilance system. However, there is limited evidence about its feasibility and validity. Systematic research should be conducted to investigate the feasibility of using social media for the pharmacovigilance system.

Introduction: The healthcare systems in many Low-and Middle-Income Countries (LMICs) like Nepal have long focused on preventing and treating infectious diseases. Little is known about their preparedness to address the increasing prevalence of Non-Communicable Diseases (NCDs). Aim: This study aimed to investigate the use of healthcare services by patients with NCDs in Nepal. Materials and Methods: Nine healthcare providers (including health assistants, pharmacy assistants, nurse, specialised nurse, practicing pharmacists, chief hospital pharmacist, doctors and specialised doctor) from Pokhara, Nepal, were recruited using purposive sampling. In depth interviews about the magnitude of NCDs, first point of care, screening and diagnosis, prevention and management, follow-up, and healthcare system responses to NCD burden were conducted. Data were thematically analysed with a deductive approach. Results: Although the healthcare system in Nepal is still primarily focused on communicable infectious diseases, healthcare providers are aware of the increasing burden of NCDs and NCD risk factors. The first points of care for patients with NCDs are government primary healthcare facilities and private pharmacies. NCDs are often diagnosed late and opportunistically. NCD prevention and treatment is unaffordable for many people. There are no government sponsored NCD screening programs. Conclusion: There are problems associated with screening, diagnosis, treatment and follow-up of patients with NCDs in Nepal. Healthcare providers believe that the current healthcare system in Nepal is inadequate to address the growing problem of NCDs. The health system of Nepal will face challenges to incorporate programs to prevent and treat NCDs in addition to the pre-existing communicable diseases.

Nepal is one of the developing countries having many limitations in providing the quality health services to its population. In many countries, improvement in patients’ adherence to the pharmacotherapy had been one of major outcome of quality pharmaceutical services. Till date, very less thing has been done in this area in Nepal; so it seems mandatory to improve the patient adherence to the treatment plans. Adherence to the medical therapy can be explained by the extent of the behavioral coincidence to the medication and non-medication regimen by a patient whereas compliance and concordance are two different models of patient adherence to the therapy. Compliance model suggests that patients have been brought responsible for being unable to follow ‘doctor’s order and concordance tempts to measure the degree of agreement between patient and his or her clinician about the nature of illness and the best possible therapy for the welfare of the patient. Non-adherence to the therapy may lead to different problems as consequences of non-adherence in four different level- individual, institutional, societal and national levels. Although some programs like, “Direct Observation Treatment, Short-course (DOTS) for tuberculosis, implementation of antiretroviral treatment schedules for HIV patients and pediatric vaccination models,” are the examples of attention towards the cases of noncompliance in Nepal. It has long been faced its limitations in the forms of either untrained manpower or lack of good documentation of patients’ adherence to therapy or high illiteracy rate or unaffordibility of patients to their treatment or lack of pharmaceutical care services.