Patient-based evidence: its role in decision making on end-of-life, orphan, and ultra-orphan medicines.

OBJECTIVES: The Scottish Medicines Consortium (SMC) conducts early health technology assessment (HTA) of new medicines on behalf of NHSScotland. Assessment of end-of-life (EoL), orphan, and ultra-orphan medicines includes a process to gather evidence from patients and carers during Patient and Clinician Engagement (PACE) meetings. The output of PACE meetings is a consensus statement describing the medicine's added value from the perspective of patients/carers and clinicians. The PACE statement is used by SMC committee members in decision making. This study compared how PACE participants and SMC committee members rate the importance of information in PACE statements for these medicines. METHODS: A survey was undertaken of patient group (PG) representatives and clinicians who participated in PACE meetings, and SMC committee members. RESULTS: PACE participants who responded (26 PG representatives and 14 clinicians) rated health benefits and ability to take part in normal life as important/very important. Convenience of administration and treatment choice received the lowest rating. Hope for the future received the most diverse response. PACE participants generally rated the importance of quality of life themes higher than committee members (n = 20) but the rank order was similar. Differences between the proportion of PACE participants and committee members who rated themes as important/very important were greatest for treatment choice and hope for the future. CONCLUSIONS: In general, PACE themes and subthemes that were rated highly by PACE participants were also considered important by SMC committee members, indicating that information captured during PACE meetings is relevant when making decisions on EoL, orphan, and ultra-orphan medicines.

Development of an international template to support patient submissions in Health Technology Assessments.

OBJECTIVES: To develop an international template to support patient submissions in Health Technology Assessments (HTAs). This was to be based on the experience and feedback from the implementation and use of the Scottish Medicines Consortium's (SMC) Summary Information for Patient Groups (SIP). METHODS: To gather feedback on the SMC experience, web-based surveys were conducted with pharmaceutical companies and patient groups familiar with the SMC SIP. Semistructured interviews with representatives from HTA bodies were undertaken, along with patient group discussions with those less familiar with the SIP, to explore issues around the approach. These qualitative data informed the development of an international SIP template. RESULTS: Survey data indicated that 82 percent (18 of 22 respondents) of pharmaceutical company representatives felt that the SIP was worthwhile; 88 percent (15/17) of patient group respondents found the SIP helpful. Both groups highlighted the need for additional support and guidance around plain language summaries. Further suggestions included provision of a glossary of terms and cost-effectiveness information. Patient group interviews supported the survey findings and led to the development of a new template. HTA bodies raised potential challenges around buy-in, timing, and bias connected to the SIP approach. CONCLUSIONS: The international SIP template is another approach to support deliberative processes in HTA. Although challenges remain around writing summaries for lay audiences, along with feasibility considerations for HTA bodies, the SIP approach should support more meaningful patient involvement in HTAs.

Assessment of Self-Administration of Romiplostim in Patients with Immune Thrombocytopenic Purpura after Receipt of Home Administration Training Materials: a Cross-Sectional Study.

INTRODUCTION: Romiplostim is a subcutaneously administered thrombopoietin-receptor agonist approved in the European Union for self-administration (or administration by a caregiver) in selected adult patients with chronic primary immune thrombocytopenia refractory to other treatments. To mitigate the risk of medication errors due to self-administration, the manufacturer has implemented additional risk minimisation measures (RMM) in the form of a Home Administration Training (HAT) pack to support the training of both healthcare professionals (HCPs) (guide and checklist for patient selection and training) and patients (a preparation mat, quick guide booklet, step-by-step guide, self-administration diary and DVD/video). OBJECTIVE: The primary objective was to estimate the proportion of patients/caregivers who administered romiplostim correctly after HAT pack training. METHODS: A multicentre observational study was conducted to evaluate the effectiveness of the HAT pack by recording data on a standardised collection form during direct observation of patients/caregivers in the act of administering romiplostim at the first standard-of-care visit 4 weeks after training with the HAT pack. RESULTS: Among the 40 patients/caregivers enrolled across 12 study centres in eight European countries, 35 [87.5%; 95% confidence interval (CI) 73.9-94.5] administered romiplostim correctly, and five (12.5%; 95% CI 5.5-26.1) did not. CONCLUSION: The correct administration of romiplostim by most patients/caregivers supports the effectiveness of the HAT pack as an additional risk minimisation tool in the population and setting of this study.

Exploring patient-reported outcomes of home-based cardiac rehabilitation in relation to Scottish, UK and European guidelines: an audit using qualitative methods.

OBJECTIVES: The Heart Manual (HM) is the UK's leading facilitated home-based cardiac rehabilitation (CR) programme for individuals recovering from myocardial infarction and revascularisation. This audit explored patient-reported outcomes of home-based CR in relation to current Scottish, UK and European guidelines. SETTING: Patients across the UK returned their questionnaire after completing the HM programme to the HM Department (NHS Lothian). PARTICIPANTS: Qualitative data from 457 questionnaires returned between 2011 and 2018 were included for thematic analysis. Seven themes were identified from the guidelines. This guided initial deductive coding and provided the basis for inductive subthemes to emerge. RESULTS: Themes included: (1) health behaviour change and modifiable risk reduction, (2) psychosocial support, (3) education, (4) social support, (5) medical risk management, (6) vocational rehabilitation and (7) long-term strategies and maintenance. Both (1) and (2) were reported as having the greatest impact on patients' daily lives. Subthemes for (1) included: guidance, engagement, awareness, consequences, attitude, no change and motivation. Psychosocial support comprised: stress management, pacing, relaxation, increased self-efficacy, validation, mental health and self-perception. This was followed by (3) and (4). Patients less frequently referred to (5), (6) and (7). Additional themes highlighted the impact of the HM programme and that patients attributed the greatest impact to a combination of all the above themes. CONCLUSIONS: This audit highlighted the HM as comprehensive and inclusive of key elements proposed by Scottish, UK and EU guidelines. Patients reported this had a profound impact on their daily lives and proved advantageous for CR.

The evaluation of operating Animal Bite Treatment Centers in the Philippines from a health provider perspective.

BACKGROUND: The Philippine government has an extensive network of 513 Animal Bite Treatment Centers (ABTCs) to supply rabies post exposure prophylaxis (PEP), reaching over 1 million bite victims in 2016. The network was evaluated using a review of existing national and provincial data, key informant interviews and surveys in sample ABTCs to determine the cost-effectiveness of this network in preventing human rabies deaths. METHODOLOGY AND PRINCIPAL FINDINGS: One urban and one rural ABTC in each of three selected provinces were studied in more detail. PEP delivery generally followed national guidance based on best practices, but there was evidence of operational challenges in supplying all ABTCs with adequate biologics and recently trained staff. Funding was contributed by different levels of government and in some clinics, patients paid for a significant fraction of the total cost. From a health provider perspective including both fixed and variable costs, the average PEP course delivered cost USD 32.91 /patient across urban ABTCs (with higher patient throughput) and USD 57.21 /patient across rural ABTCs. These costs suggests that PEP provision in the Philippines cost USD 37.6 million in 2016, with a cost per life saved of USD 8,290. An analysis of the 2,239 suspected rabies deaths from 2008 to 2016 showed no significant decline, and from 2014-16 an average of 8,534 years of life were lost annually. The incidence of rabies deaths from 2014-16 was not clearly related to the provision of ABTCs (per 100,000 population) or human population density, but deaths were more common in higher income provinces. CONCLUSIONS/SIGNIFICANCE: In the context of comprehensive rabies control (including dog vaccination and public awareness) ways to reduce this high expenditure on PEP should be explored, to most cost-effectively reach the elimination of human rabies deaths. This paper is accompanied by another containing data on the operation of ABTCs network from a patient perspective.

The Ilocos Norte Communities against Rabies Exposure Elimination Project in the Philippines: Epidemiological and Economic Aspects.

As canine rabies control in Africa and Asia transitions from research-led proof-of-concept studies to government-led programs for elimination, experience and evidence of their impact and costs must be shared for the benefit of future programs. The Ilocos Norte Communities against Rabies Exposure project was implemented in April 2012 by the provincial veterinary and health offices and supported by many other partners. It delivered a comprehensive dog vaccination program and increased awareness of the need for postexposure prophylaxis (PEP), aiming to eliminate human and animal rabies cases from Ilocos Norte by 2015. Prior to the intervention, confirmed rabies cases in dogs were between 19 and 50 per year (2008-2011). The primary outcome of the project was a reduction in rabies cases in both dogs and humans to 0 in 2014 and 2015, which has subsequently been maintained. Animal bite consultations increased significantly during the project. Economic data for the dog vaccination and PEP components of the project were collated for two sites: Laoag City (an urban setting) and Dingras Municipality (a rural setting) between 2012 and 2014. The average programmatic cost of vaccinating each dog was $4.54 in Laoag City and $8.65 in Dingras, and costs fell as the project reached more dogs. The average costs of providing PEP were $69.72 per patient and $49.02 per patient for the two sites, respectively, again falling as the project reached more people. External donor contributions contributed less than 20% of dog vaccination costs and less than 1% of PEP costs. The project demonstrated that rabies elimination can be achieved in a short period of time, with concerted effort across multiple sectors. A lack of clear dog population estimates hampered interpretation of some aspects of the programme. From 2016, the provincial government has assumed complete responsibility for the programme and must now continue the vaccination and surveillance efforts. Although safeguards are in place, reintroduction from surrounding areas remains a threat, and vigilance must be maintained.

Effectiveness of a stepwise Pseudomonas aeruginosa eradication protocol in children with cystic fibrosis.

INTRODUCTION: Antibiotic eradication therapy (AET) for initial Pseudomonas aeruginosa (Pa) infection is standard of care in children with cystic fibrosis (CF), but information is limited on treatment for patients who fail initial AET. The aim of this study was to evaluate the effectiveness of a multi-step protocol for AET for new-onset Pa infections in children with CF. METHODS: A three-step AET protocol which includes: (step 1) 28days of tobramycin inhalation solution (TIS) for new-onset Pa infection; (step 2) a second course of TIS for patients with positive respiratory tract culture after step 1; (step 3) 14days of intravenous antibiotics followed by 28days of TIS for patients with a subsequent positive culture. We conducted a retrospective review of all pediatric CF patients who underwent the eradication protocol between January 2010 and December 2015. The success rate of each step and of the overall protocol was recorded. RESULTS: During the study period, 128 patients had a total of 213 new-onset Pa infections. Of 195 asymptomatic episodes, 150 (76.9%, 95% CI 70.4; 82.6) cleared after step 1 and 12 cleared after step 2 (33.3% (95% CI 18.6; 50.9) stepwise success rate and 87.1% (95% CI 77.1; 88.1) cumulative success rate). Intravenous antibiotics followed by 28days of TIS were administered in 24 episodes; this was successful in 10 episodes (41.7%; 95% CI 22.1; 63.4). The regimen in asymptomatic patients failed in fourteen episodes (7.5%; 95% CI 4.2; 12.3) then considered chronically infected with Pa. Overall, the cumulative success rate of the asymptomatic arm was 88.2% (95% CI 82.8; 92.4). CONCLUSION: The first step of the AET protocol led to the greatest eradication success. Subsequent eradication attempts have a success rate below 50%. Prospective studies of eradication protocols for this population are needed to determine the most effective treatment strategy.

Estimating the global burden of endemic canine rabies.

BACKGROUND: Rabies is a notoriously underreported and neglected disease of low-income countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment of how much this preventable disease costs endemic countries. METHODOLOGY/PRINCIPAL FINDINGS: We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework. We used data derived from extensive literature searches and questionnaires on disease incidence, control interventions and preventative measures within this framework to estimate the disease burden. The burden of rabies impacts on public health sector budgets, local communities and livestock economies, with the highest risk of rabies in the poorest regions of the world. This study estimates that globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25-159,000) human deaths, over 3.7 million (95% CIs: 1.6-10.4 million) disability-adjusted life years (DALYs) and 8.6 billion USD (95% CIs: 2.9-21.5 billion) economic losses annually. The largest component of the economic burden is due to premature death (55%), followed by direct costs of post-exposure prophylaxis (PEP, 20%) and lost income whilst seeking PEP (15.5%), with only limited costs to the veterinary sector due to dog vaccination (1.5%), and additional costs to communities from livestock losses (6%). CONCLUSIONS/SIGNIFICANCE: This study demonstrates that investment in dog vaccination, the single most effective way of reducing the disease burden, has been inadequate and that the availability and affordability of PEP needs improving. Collaborative investments by medical and veterinary sectors could dramatically reduce the current large, and unnecessary, burden of rabies on affected communities. Improved surveillance is needed to reduce uncertainty in burden estimates and to monitor the impacts of control efforts.