Research Health Technology Assessment Research Articles

Research gaps identified in Iran’s health technology assessment reports

IntroductionIdentifying gaps in the evidence is a useful byproduct of conducting a health technology assessment (HTA). This study aims to identify research gaps in Iran’s HTA reports.MethodWe reviewed the HTA reports published between 2014 and 2016. Then, we developed two separate questionnaires for principal investigators (PIs) and independent HTA researchers. The questionnaire for independent HTA researchers consisted of four main parts. However, the PIs’ questionnaire consisted of two main parts. We also conducted a literature search in the PubMed database in November 2017 to find frameworks for prioritizing research gaps. We also conducted a semi-structured interview with the head of the Iran’s HTA Office at that time and sought feedback based on his expert opinion about questionnaires, the priority-setting tool and our process for extracting research gaps.ResultsA total of 11 HTA reports published between 2014 and 2016 by Iran’s HTA Office were selected for the study. Of these 11 reports, 5 involved technologies related to medical equipment, while 6 involved medical and surgical interventions. Assessing the outcomes of technology use in various indications and updating HTAs when new evidence arises; evaluating the viewpoints of patients, clinicians and key technology users; conducting post-marketing evaluations of technology; comparing the impact of the technology in question to other treatments for the same condition; and requesting long-term clinical and cost–effectiveness data for technologies with limited follow-up periods were identified as the main gaps by independent HTA researchers and PIs.ConclusionsThe research gaps identified from Iran’s HTAs could be utilized by research funding agencies.

OP07 Eleven Years Of Conitec: Advances And Challenges Of Patient And Public Involvement In The Brazilian Health Technology Assessment Process

IntroductionPatient and public involvement (PPI) is a core element of the health technology assessment (HTA) process. Since its creation in 2011, the National Committee for Health Technology Incorporation (Conitec) has promoted initiatives to include stakeholders in HTA for the Brazilian Public Health System (SUS). This work aimed to present a report on the advances and challenges related to PPI in 11 years of Conitec.MethodsA retrospective analysis of PPI actions carried out at Conitec was conducted, based on an analysis of minutes and records of meetings and discussions held internally and documents published on Conitec´s website.ResultsEvents and meetings were held over the years with different actors interested in the HTA process. Since 2015, a plain-language version of the technical report has been made available to the public during public consultations for each HTA topic. Recently, a register of patients, specialists, and SUS managers was created to form a database and establish a network with the stakeholders. Since 2020, SUS users have been allocated time to speak at Conitec´s meetings. Qualitative analysis of public consultation documents started in 2021 and a pilot qualitative evidence synthesis was carried out in 2022. These initiatives, although not directly focused on PPI, increase the consideration of the perspectives of patients, family members, and caregivers in the HTA process.ConclusionsPPI actions implemented at Conitec have significantly promoted inclusiveness and exchanges among stakeholders, contributing to a greater transparency regarding Conitec’s actions. Nonetheless, we have important challenges on our horizon, such as strengthening connections with primary healthcare managers and professionals and social movements. It is also strategic to expand the technical and scientific discussion on PPI and qualitative approaches with HTA researchers and the voting members of Conitec. Finally, another aim is to improve knowledge of HTA and public health policy among law professionals and the pharmaceutical industry in Brazil.

OP66 Adoption Of The World Health Organization Algorithm For Essential Medicines In The Philippine National Formulary Listing Process

IntroductionThe Philippine National Formulary (PNF) System preceded the health technology assessment (HTA) process in the Philippines, which was institutionalized in 2019. The transition led to previously prioritized topics of expert bodies overseeing the PNF System being endorsed to the HTA Council. However, the advent of COVID-19 forced the HTA Philippines to focus on emergency assessment needs and financing recommendations for the national government, resulting in limited capacity to assess non-public health emergency topics. To address this and improve patient access to medicines, we adopted the World Health Organization (WHO) process for evaluating and selecting medicines in the National Essential Medicines List (NEML).MethodsIn assessing the pre-pandemic topics, we matched the population, intervention, comparator, and outcomes of the WHO clinical evidence reviews with those scoped with relevant stakeholders and performed local costing analyses to ensure applicability of findings to the Philippine setting. When needed, we subjected the topics to price negotiation or conducted qualitative assessments.ResultsWe found the method efficient in expediting the decision-making process of the HTA Council. However, given the limited internal capacity of the HTA Philippines to conduct assessments for all ongoing HTA tracks, some of the topics responsive to Universal Health Care will be outsourced to the HTA Research Network, which is yet to be established. There is also a need to improve alignment among the topics being assessed, since the priorities of the proponents, national health program, and national payer have already evolved.ConclusionsIt is important to identify the priority areas for stakeholders as part of the topic nomination process, account for analytic capacity when setting the number of topics for HTA, establish mechanisms to allow proponents to conduct HTAs based on the HTA Council’s methodological standards, and proactively work with the national regulatory agency on horizon scanning and early HTA. We also recommend efficient monitoring, evaluation, and updating of the Philippine HTA guidelines so that they are more responsive to the needs of the healthcare system and the Filipino people.

Evaluating the quality of health technology assessment reports in a developing country.

No single method of health technology assessment (HTA) can meet all the policy- and decision-making needs in a country. However, there should be minimum criteria for performing HTA worldwide, and many HTA agencies have reached a consensus on this. This study aimed to assess the quality of HTA reports in the Islamic Republic of Iran. We examined all the HTA research reports published by the Iranian HTA office up to 2020, using the International Network of Agencies for Health Technology Assessment checklist for quality assessment. A total of 97 reports were examined, of which only 10.0% provided complete and appropriate contact details for further information and 5.6% clearly stated a conflict of interest. In 87.78% of the reports, the scope of assessment was clearly determined. The quality of the reports was relatively appropriate as well as details of the sources of information and text search strategies. Some 7.8%, 74.4%, 11.1%, 8.9%, and 4.4%, respectively, of the reports considered legal aspects, economic analysis, ethical implications, social implications, and other stakeholder perspectives. We recommend that minimum standards be established for the HTA process so that healthcare policy- and decision-makers can make reliable decisions on the basis of the HTA reports.

A SWOT analysis of the development of health technology assessment in Iran.

Health systems need to prioritize their services, ensuring efficiency and equitable health provision allocation and access. Alongside, health technology assessment (HTA) seeks to systematically evaluate various aspects of health technologies to be used by policy- and decision-makers. In the present study, we aim to identify strengths, weaknesses, opportunities, and threats in developing an HTA in Iran. This qualitative study was conducted using 45 semi-structured interviews from September 2020 to March 2021. Participants were selected from key individuals involved in health and other health-related sectors. Based on the objectives of the study, we used purposive sampling (snowball sampling) to select individuals. The range of length of the interviews was between 45 to 75 minutes. Four authors of the present study carefully reviewed the transcripts of interviews. Meanwhile, the data were coded on the four domains of strengths, weaknesses, opportunities, and threats (SWOT). Transcribed interviews were then entered into the software and analyzed. Data management was performed using MAXQDA software, and also analyzed using directed content analysis. Participants identified eleven strengths for HTA in Iran, namely the establishment of an administrative unit for HTA within the Ministry of Health and Medical Education (MOHME); university-level courses and degrees for HTA; adapted approach of HTA models to the Iranian context; HTA is mentioned as a priority on the agenda in upstream documents and government strategic plans. On the other hand, sixteen weaknesses in developing HTA in Iran were identified: unavailability of a well-defined organizational position for using HTA graduates; HTA advantages and its basic concept are unfamiliar to many managers and decision-makers; weak inter-sectoral collaboration in HTA-related research and key stakeholders; and, failure to use HTA in primary health care. Also, participants identified opportunities for HTA development in Iran: support from the political side for reducing national health expenditures; commitment and planning to achieve universal health coverage (on behalf of the government and parliament); improved communication among all stakeholders engaged in the health system; decentralization and regionalization of decisions; and capacity building to use HTA in organizations outside the MOHME. High inflation and bad economic situation; poor transparency in decisions; lack of support from insurance companies; lack of sufficient data to conduct HTA research; rapid change of managers in the health system; and economic sanctions against Iran are threats to the developmental path of HTA in Iran. HTA can be properly developed in Iran if we use its strengths and opportunities, and address its weaknesses and threats.

Identifying Attributes for a Value Assessment Framework in China: A Qualitative Study.

Value assessment frameworks (VAFs) are promising tools for measuring the value of health technologies and informing coverage policymaking; however, most published VAFs were developed for high-income countries. This study aimed to identify value attributes as part of the development of a VAF in China. We used the qualitative description approach. Specifically, we conducted open-ended semi-structured interviews with Chinese stakeholders, as well as a review and analysis of publicly available government documents related to health technology assessment (HTA) and coverage policies in China. Conventional content analysis and the constant comparison technique were used to generate value attributes. Multiple criteria were used to determine the inclusion of a value attribute, with response levels of included attributes finalized via consensus meetings among the research team. Thirty-four stakeholders living or working in China completed the semi-structured interview. These stakeholders included policymakers (n=4), healthcare providers (n=8), HTA researchers (n=6), patients and members of the general public (n=9), and industry representatives (n=7). In addition, 16 government documents were included for analysis. Twelve value attributes grouped in eight categories are included in the VAF: (1) severity of disease; (2) health benefit, including survival, clinical outcomes, and patient-reported outcomes; (3) safety; (4) economic impact, including budget impact to payer and patients, and cost effectiveness; (5) innovation; (6) organizational impact; (7) health equity; and (8) quality of evidence. These 12 value attributes were identified for the development of a VAF to support health technologies' value assessment and coverage policymaking in China.

Current status of health technology assessment research in Japan.

Health technology assessment (HTA) is implemented in the decision-making process for the reimbursement and pricing of drugs and medical devices around the world. This study presented the trend and characteristics of HTA research in Japan and worldwide. HTA research increased since the 2010s. Cancer was a prominent subject and the Markov model was a major analytical model in HTA research both globally and in Japan. In Japan, osteoporosis was a more popular topic, but there were fewer surgical research and review articles compared to the global trend. Since Japanese articles on HTA were much fewer than those from the United States, the United Kingdom, and China, various types of HTA research should be encouraged in Japan to promote product innovation and optimize medical expenditures.

The long process by which HTA became a paradigm: A longitudinal conceptual structure analysis

This study maps the conceptual structure of health technology assessment (HTA) research with the aim of contributing to a better understanding of this research stream. A bibliometric analysis of 1,198 HTA articles retrieved from the Web of Science database was conducted. The analysis of descriptive performance indicators identified the main traits of the scientific debate about the HTA in terms of publications, productive countries, and sources. A co-word analysis was performed by adopting social network analysis tools to map the conceptual structure of the dataset. The results highlight the growing academic interest in the research topic, especially in recent years. The results revealed that HTA is a widely known term and represents the reference paradigm for assessment in healthcare technologies. This paper contributes to the field by providing an examination of the current state of the art of HTA research and identifying possible future research directions. This study differs from existing studies because it involved a conceptual analysis of the scientific literature using macro keywords.

PP128 Development And Piloting Of An Online Training Course On Health Technology Assessment For Patients

IntroductionPatients have knowledge, perspectives and experiences that are unique and can make an essential contribution to Health Technology Assessment (HTA). However, in order for their participation to be effective, they need to be able to understand how HTA reports are generated and the decision-making processes that they inform. The aim is to describe the development and virtualization of training materials for patients, as well as to their implementation in a pilot study.MethodsA working group from Spanish Network of Agencies for Assessing National Health System Technologies and Performance (RedETS) agencies was created to develop educational materials in collaboration with patients. The content was based on international initiatives and feedback from the working group. The project was initiated in November 2020. The team consisted of HTA researchers, technicians with experience in training and virtualization and patients. The final version was obtained after an iterative process and refinement of the content and design.ResultsThe materials were published in complete and summary versions, and they were translated into Catalan, Basque and Galician. The online course was designed in an e-learning platform (Moodle) with the aim of being implemented by each of the agencies. The materials include relevant and summarized information on HTA processes, current framework at national and European level, and the role of patients in HTA. Health research and the importance of qualitative and quantitative methods are also addressed. The course also includes a module of practical aspects of patient and citizen participation for achieving an effective contribution to HTA. The course is being piloted with patients in different regions in Spain. The objective of the pilot is to evaluate the usefulness and satisfaction with the course, and it has been designed with the purpose of incorporating the pertinent modifications in the course.ConclusionsThe online training course is intended to facilitate the acquisition of knowledge related to the processes and tools of HTA for patients, as well as to inform them in what phases and in what way they can participate. The pilot will provide relevant information on its use in practice. It is expected that the course will favor capacity building and patient involvement.

Some considerations on target estimands for health technology assessment.

Some considerations on target estimands for health technology assessment.

A Review on Existing Health Technology Assessment (HTA) Methodologies

Health technology assessment (HTA) generally means the step by step procedure to analyze the efficiency and effectiveness of a health technology. The COVID-19 pandemic situation has been made us realized about the important of HTA. For instance, before providing the vaccine for coronavirus, the vaccines need to be trialed for proofing its efficiency and effectiveness and this whole procedure of clinical trial is known as health technology assessment. This review has studied the definitions of HTA provided by international HTA agencies and researchers, and proposes a working definition of HTA. Moreover, this study broadly describes the framework and methodologies of conducting HTA for a health technology. In COVID-19 situation, it is necessary to find a suitable method to assess coronavirus vaccines to identify its efficiency and effectiveness. This study will be helpful for the HTA conducting authorities to find a suitable way to assess vaccines. In addition, this study has pinpointed the current study gaps in HTA and suggested few recommendations to address HTA at present.

Arthroscopic hip surgery compared with personalised hip therapy in people over 16 years old with femoroacetabular impingement syndrome: UK FASHIoN RCT.

Femoroacetabular impingement syndrome is an important cause of hip pain in young adults. It can be treated by arthroscopic hip surgery or with physiotherapist-led conservative care. To compare the clinical effectiveness and cost-effectiveness of hip arthroscopy with best conservative care. The UK FASHIoN (full trial of arthroscopic surgery for hip impingement compared with non-operative care) trial was a pragmatic, multicentre, randomised controlled trial that was carried out at 23 NHS hospitals. Participants were included if they had femoroacetabular impingement, were aged ≥ 16 years old, had hip pain with radiographic features of cam or pincer morphology (but no osteoarthritis) and were believed to be likely to benefit from hip arthroscopy. Participants were randomly allocated (1 : 1) to receive hip arthroscopy followed by postoperative physiotherapy, or personalised hip therapy (i.e. an individualised physiotherapist-led programme of conservative care). Randomisation was stratified by impingement type and recruiting centre using a central telephone randomisation service. Outcome assessment and analysis were masked. The primary outcome was hip-related quality of life, measured by the patient-reported International Hip Outcome Tool (iHOT-33) 12 months after randomisation, and analysed by intention to treat. Between July 2012 and July 2016, 648 eligible patients were identified and 348 participants were recruited. In total, 171 participants were allocated to receive hip arthroscopy and 177 participants were allocated to receive personalised hip therapy. Three further patients were excluded from the trial after randomisation because they did not meet the eligibility criteria. Follow-up at the primary outcome assessment was 92% (N = 319; hip arthroscopy, n = 157; personalised hip therapy, n = 162). At 12 months, mean International Hip Outcome Tool (iHOT-33) score had improved from 39.2 (standard deviation 20.9) points to 58.8 (standard deviation 27.2) points for participants in the hip arthroscopy group, and from 35.6 (standard deviation 18.2) points to 49.7 (standard deviation 25.5) points for participants in personalised hip therapy group. In the primary analysis, the mean difference in International Hip Outcome Tool scores, adjusted for impingement type, sex, baseline International Hip Outcome Tool score and centre, was 6.8 (95% confidence interval 1.7 to 12.0) points in favour of hip arthroscopy (p = 0.0093). This estimate of treatment effect exceeded the minimum clinically important difference (6.1 points). Five (83%) of six serious adverse events in the hip arthroscopy group were related to treatment and one serious adverse event in the personalised hip therapy group was not. Thirty-eight (24%) personalised hip therapy patients chose to have hip arthroscopy between 1 and 3 years after randomisation. Nineteen (12%) hip arthroscopy patients had a revision arthroscopy. Eleven (7%) personalised hip therapy patients and three (2%) hip arthroscopy patients had a hip replacement within 3 years. Study participants and treating clinicians were not blinded to the intervention arm. Delays were encountered in participants accessing treatment, particularly surgery. Follow-up lasted for 3 years. Hip arthroscopy and personalised hip therapy both improved hip-related quality of life for patients with femoroacetabular impingement syndrome. Hip arthroscopy led to a greater improvement in quality of life than personalised hip therapy, and this difference was clinically significant at 12 months. This study does not demonstrate cost-effectiveness of hip arthroscopy compared with personalised hip therapy within the first 12 months. Further follow-up will reveal whether or not the clinical benefits of hip arthroscopy are maintained and whether or not it is cost-effective in the long term. Current Controlled Trials ISRCTN64081839. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 16. See the NIHR Journals Library website for further project information.

Moulded cast compared with K-wire fixation after manipulation of an acute dorsally displaced distal radius fracture: the DRAFFT 2 RCT.

Patients with a displaced fracture of the distal radius are frequently offered surgical fixation. Manipulation of the fracture and moulded plaster casting is an alternative treatment that avoids metal implants, but evidence of its effectiveness is lacking. To compare functional outcomes, quality-of-life outcomes, complications and resource use among patients with a dorsally displaced fracture of the distal radius treated with manipulation and surgical fixation with Kirschner wires (K-wires) and those treated with manipulation and moulded cast. Pragmatic, superiority, multicentre, randomised controlled trial with a health economic evaluation. A total of 36 orthopaedic trauma centres in the UK NHS. Patients (aged ≥ 16 years) treated for an acute dorsally displaced fracture of the distal radius were potentially eligible. Patients were excluded if their injury had occurred > 2 weeks previously, if the fracture was open, if it extended > 3 cm from the radiocarpal joint or if it required open reduction, or if the participant was unable to complete questionnaires. Participants were randomly assigned in theatre (1 : 1) to receive a moulded cast (i.e. the cast group) or surgical fixation with K-wires (i.e. the K-wire group) after fracture manipulation. The primary outcome measure was the Patient-Rated Wrist Evaluation score at 12 months, analysed on an intention-to-treat basis. Health-related quality of life was recorded using the EuroQol-5 Dimensions, five-level version, and resource use was recorded from a health and personal social care perspective. Between January 2017 and March 2019, 500 participants (mean age 60 years, 83% women) were randomly allocated to receive a moulded cast (n = 255) or surgical fixation with K-wire (n = 245) following a manipulation of their fracture. A total of 395 (80%) participants were included in the primary analysis at 12 months. There was no difference in the Patient-Rated Wrist Evaluation score at 1 year post randomisation [cast group: n = 200, mean score 21.2 (standard deviation 23.1); K-wire group: n = 195, mean score 20.7 (standard deviation 22.3); adjusted mean difference -0.34 (95% confidence interval -4.33 to 3.66); p = 0.87]. A total of 33 (13%) participants in the cast group required surgical fixation for loss of fracture position in the first 6 weeks, compared with one participant in the K-wire group (odds ratio 0.02, 95% confidence interval 0.001 to 0.10). The base-case cost-effectiveness analysis showed that manipulation and surgical fixation with K-wires had a higher mean cost than manipulation and a moulded cast, despite similar mean effectiveness. The use of K-wires is unlikely to be cost-effective, and sensitivity analyses found this result to be robust. Because the interventions were identifiable, neither patients nor clinicians could be blind to their treatment. Surgical fixation with K-wires was not found to be superior to moulded casting following manipulation of a dorsally displaced fracture of the distal radius, as measured by Patient-Rated Wrist Evaluation score. However, one in eight participants treated in a moulded cast required surgery for loss of fracture reduction in the first 6 weeks. After a successful closed reduction, clinicians may consider a moulded cast as a safe and cost-effective alternative to surgical fixation with K-wires. Further research should focus on optimal techniques for immobilisation and manipulation of this type of fracture, including optimal analgesia, and for rehabilitation of the patient after immobilisation. This trial is registered as ISRCTN11980540 and UKCRN Portfolio 208830. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 11. See the NIHR Journals Library website for further project information.

Can We Afford to Exclude Patients Throughout Health Technology Assessment?

Health technology assessment (HTA) is intended to determine the value of health technologies and, once a technology is recommended for funding, bridge clinical research and practice. Understanding the values and beliefs expressed by patients and health professionals can help guide this knowledge transfer and work toward managing the expectations of end users. We gathered patient and patient group leader experiences to gain insights into the roles that patients and patient advocacy groups are playing. We argue that through partnerships and co-creation between HTA professionals, researchers and patient advocates we can strengthen the HTA process and better align with service delivery where person-centered care and shared decision making are key elements. Patient experiences and knowledge are important to the democratization of evidence and the legitimacy of HTAs. Patient preference studies are used to balance benefits with potential harms of technologies, and patient-reported outcomes (PROs) can measure what matters to patients over time. A change in culture in HTA bodies is occurring and with further transformative thinking patients can be involved in every step of the HTA process. Patients have a right to be involved in HTAs, with patients' values central to HTA deliberations on a technology and where patients can provide valuable insights to inform HTA decision-making; and in ensuring that HTA methodologies evolve. By evaluating the implementation of HTA recommendations we can determine how HTA benefits patients and their communities. Our shared commitment can positively effect the common good and provide benefits to individual patients and their communities.

Integrating organizational impacts into health technology assessment (HTA): an analysis of the content and use of existing evaluation frameworks.

The French health technology assessment (HTA) agency initiated a research between 2018 and 2019 with the aim of determining whether other HTA organizations (agencies, bodies, institutes, and expert networks) and researchers had developed an evaluation framework of organizational impacts (OIs). Three types of investigation were carried out: (i) an analysis of documents published by selected HTA organizations, (ii) a rapid review on the OI issues, (iii) a questionnaire survey to experts of the International Network of Agencies for Health Technology Assessment. The analyses highlight six key points: (i) there is no explicit conceptual definition of OIs; (ii) OIs are often not included in a specific dimension of the evaluation or in the same dimensions; (iii) three recurring categories emerge from the assessment of OIs: processes, structure, and culture; (iv) despite its limitations, the European Network for Health Technology Assessment framework (Core Model) is the most mature assessment model to date; (v) the question of the scope of OIs to be considered is unresolved (micro-meso-macro); and (vi) the delineation between OI assessment and economic assessment must be addressed. Although the issue of considering OI in HTA has been raised for many years, it remains largely unresolved. Defining the concept of OI is a prerequisite for taking the next step toward an evaluation framework. As the question of the impact of innovation goes beyond the health sector, extensive research on how to define and take into account these OIs may be relevant.

OP244 Tools And Experiences To Facilitate Effective Patient Participation In Health Technology Assessment

IntroductionIn 2017, a Patient Involvement Interest Group (PIIG) was created in the Spanish Network for Health Technology Assessment of the National Health System (RedETS) to facilitate and promote Patient Involvement (PI) in Health Technology Assessment (HTA). The PIIG proposed a decisional flowchart to guide researchers’ in decisions regarding PI methods in HTA. The flowchart proposed a combination of direct involvement and incorporation of patient-based evidence depending on the scope and the aims of the assessment.This work aims to present the flowchart and the results of the evaluation of the latest experiences in PI in HTA in RedETS (2018–2020), including direct-involvement and patient-based evidence.MethodsA survey was sent to the HTA researchers who implemented PI initiatives in RedETS assessments. The survey asked to describe their experiences, lessons learned, challenges and added value regarding the use of direct-involvement, systematic reviews (SR) and primary studies. A descriptive analysis was performed and the results were discussed in an online PIIG workshop.ResultsThirty-two assessments included direct PI, twenty-one SR synthesized qualitative and quantitative studies about patient experiences, values and preferences and eight included primary studies, mainly of qualitative design. Recruitment and the lack of methodological resources were the main barriers both for direct PI and primary studies. Relevance of the included studies was the main barrier for SR. Added value was found in all PI methods. Direct-involvement had an impact on the project plan and PICO definition, outcomes relevance, information about the health condition and treatments. SR contributed with relevant patient-based evidence, deeper assessment of patient experiences, values and preferences and implementation factors. Primary studies developed new or contextualized knowledge directly applicable to decision-making.ConclusionsThe PI flowchart has served to facilitate the incorporation of patient input in HTA reports. The different approaches implemented have allowed to provide relevant and well-grounded data in each report to inform decision-making in patient-centered healthcare provision, but it is necessary that specific training and resources are provided to enable adequate and timely implementation.

Ondansetron and metoclopramide as second-line antiemetics in women with nausea and vomiting in pregnancy: the EMPOWER pilot factorial RCT.

Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There is no cure for nausea and vomiting in pregnancy. Management focuses on relieving symptoms and preventing morbidity, and often requires antiemetic therapy. National guidelines make recommendations about first-, second- and third-line antiemetic therapies, although care varies in different hospitals and women report feeling unsupported, dissatisfied and depressed. To determine whether or not, in addition to intravenous rehydration, ondansetron compared with no ondansetron and metoclopramide compared with no metoclopramide reduced the rate of treatment failure up to 10 days after drug initiation; improved symptom severity at 2, 5 and 10 days after drug initiation; improved quality of life at 10 days after drug initiation; and had an acceptable side effect and safety profile. To estimate the incremental cost per treatment failure avoided and the net monetary benefits from the perspectives of the NHS and women. This was a multicentre, double-dummy, randomised, double-blinded, dummy-controlled 2 × 2 factorial trial (with an internal pilot phase), with qualitative and health economic evaluations. Thirty-three patients (who were < 17 weeks pregnant and who attended hospital with nausea and vomiting after little or no improvement with first-line antiemetic medication) who attended 12 secondary care NHS trusts in England, 22 health-care professionals and 21 women participated in the qualitative evaluation. Participants were randomly allocated to one of four treatment groups (1 : 1 : 1: 1 ratio): (1) metoclopramide and dummy ondansetron; (2) ondansetron and dummy metoclopramide; (3) metoclopramide and ondansetron; or (4) double dummy. Trial medication was initially given intravenously and then continued orally once women were able to tolerate oral fluids for a maximum of 10 days of treatment. The primary end point was the number of participants who experienced treatment failure, which was defined as the need for further treatment because symptoms had worsened between 12 hours and 10 days post treatment. The main economic outcomes were incremental cost per additional successful treatment and incremental net benefit. Of the 592 patients screened, 122 were considered eligible and 33 were recruited into the internal pilot (metoclopramide and dummy ondansetron, n = 8; ondansetron and dummy metoclopramide, n = 8; metoclopramide and ondansetron, n = 8; double dummy, n = 9). Owing to slow recruitment, the trial did not progress beyond the pilot. Fifteen out of 30 evaluable participants experienced treatment failure. No statistical analyses were performed. The main reason for ineligibility was prior treatment with trial drugs, reflecting an unpredicted change in prescribing practice at several points along the care pathway. The qualitative evaluation identified the requirements of the study protocol, in relation to guidelines on anti-sickness drugs, and the diversity of pathways to care as key hurdles to recruitment while the role of research staff was a key enabler. No important adverse events or side effects were reported. The pilot trial failed to achieve the recruitment target owing to unforeseen changes in the provision of care. The trial was unable to provide evidence to support clinician decisions about the best choice of second-line antiemetic for nausea and vomiting in pregnancy. Current Controlled Trials ISRCTN16924692 and EudraCT 2017-001651-31. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 63. See the NIHR Journals Library website for further project information.

A model of lifetime health outcomes in cardiovascular disease based on clinical trials and large cohorts

Abstract Background and purpose Cardiovascular disease (CVD) risk of individuals depends on their socio-demographic characteristics, clinical risk factors, and treatments, and strongly influences their quality of life and survival. Individual-based long-term disease models, which aim to more accurately calculate the lifetime consequences, can help to target treatments, develop disease management programmes, and assess the value of new therapies. We present a new micro-simulation CVD model. Methods This micro-simulation model was developed using individual participant data from the Cholesterol Treatment Trialists' collaboration (CTT: 118,000 participants; 15 trials) and calibrated (with added socioeconomic deprivation, ethnicity, physical activity, mental illness, cancer and incident diabetes) in the UK Biobank cohort (UKB: 502,000 participants). Parametric survival models estimated risks of key endpoints (myocardial infarction (MI), stroke, coronary revascularisation (CRV), diabetes, cancer and vascular (VD) and nonvascular death (NVD) using participants' age, sex, ethnicity, physical activity, socioeconomic deprivation, smoking history, lipids, blood pressure, creatinine, previous cardiovascular diseases, diabetes, mental illness and cancer at entry and non-fatal incidents of the key endpoints during follow-up. The model integrates the risk equations and enables annual projection of endpoints and survival over individuals' lifetimes. The model was used to project remaining life expectancy across UK Biobank participants. Results Nonfatal cardiovascular events and age were the major determinants of CVD risk and, together with incident diabetes and cancer, of individuals' survival. The cumulative incidence of the key endpoints predicted by the CTT-UKB model corresponded well to their observed incidence in the UK Biobank cohort, overall (Figure 1) and in categories of participants by age, sex, prior CVD and CVD risk. Predicted remaining life expectancy across UK Biobank participants without history of CVD ranged between 22 and 43 years in men and between 24 and 46 years in women, depending on their age and CVD risk (Figure 2). Among UK Biobank participants with history of CVD, depending on their age, predicted remaining life expectancy ranged from 20 to 32 years in men and from 26 to 38 years in women. Conclusion This new lifetime CVD model accurately predicts morbidity and mortality in a large UK population cohort. It will be made available to provide individualised projections of expected lifetime health outcomes and benefits of treatments. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme, UK Medical Research Council (MRC), British Heart Foundation Figure 1. Predicted (in black) versus observed (95% CI; in red) incidence of major clinical outcomes in the UK Biobank.Figure 2. Predicted remaining life expectancy of participants in UK Biobank cohort, by age and CVD risk or previous CVD at entry. QRISK, a 10-year CVD risk scoring algorithm for people without previous CVD, recommended for use in the UK National Health Service.

Acceptance and commitment therapy for older people with treatment-resistant generalised anxiety disorder: the FACTOID feasibility study.

Generalised anxiety disorder, characterised by excessive anxiety and worry, is the most common anxiety disorder among older people. It is a condition that may persist for decades and is associated with numerous negative outcomes. Front-line treatments include pharmacological and psychological therapy, but many older people do not find these treatments effective. Guidance on managing treatment-resistant generalised anxiety disorder in older people is lacking. To assess whether or not a study to examine the clinical effectiveness and cost-effectiveness of acceptance and commitment therapy for older people with treatment-resistant generalised anxiety disorder is feasible, we developed an intervention based on acceptance and commitment therapy for this population, assessed its acceptability and feasibility in an uncontrolled feasibility study and clarified key study design parameters. Phase 1 involved qualitative interviews to develop and optimise an intervention as well as a survey of service users and clinicians to clarify usual care. Phase 2 involved an uncontrolled feasibility study and qualitative interviews to refine the intervention. Participants were recruited from general practices, Improving Access to Psychological Therapies services, Community Mental Health Teams and the community. Participants were people aged ≥ 65 years with treatment-resistant generalised anxiety disorder. Participants received up to 16 one-to-one sessions of acceptance and commitment therapy, adapted for older people with treatment-resistant generalised anxiety disorder, in addition to usual care. Sessions were delivered by therapists based in primary and secondary care services, either in the clinic or at participants' homes. Sessions were weekly for the first 14 sessions and fortnightly thereafter. The co-primary outcome measures for phase 2 were acceptability (session attendance and satisfaction with therapy) and feasibility (recruitment and retention). Secondary outcome measures included additional measures of acceptability and feasibility and self-reported measures of anxiety, worry, depression and psychological flexibility. Self-reported outcomes were assessed at 0 weeks (baseline) and 20 weeks (follow-up). Health economic outcomes included intervention and resource use costs and health-related quality of life. Fifteen older people with treatment-resistant generalised anxiety disorder participated in phase 1 and 37 participated in phase 2. A high level of feasibility was demonstrated by a recruitment rate of 93% and a retention rate of 81%. A high level of acceptability was found with respect to session attendance (70% of participants attended ≥ 10 sessions) and satisfaction with therapy was adequate (60% of participants scored ≥ 21 out of 30 points on the Satisfaction with Therapy subscale of the Satisfaction with Therapy and Therapist Scale-Revised, although 80% of participants had not finished receiving therapy at the time of rating). Secondary outcome measures and qualitative data further supported the feasibility and acceptability of the intervention. Health economic data supported the feasibility of examining cost-effectiveness in a future randomised controlled trial. Although the study was not powered to examine clinical effectiveness, there was indicative evidence of improvements in scores for anxiety, depression and psychological flexibility. Non-specific therapeutic factors were not controlled for, and recruitment in phase 2 was limited to London. There was evidence of high levels of feasibility and acceptability and indicative evidence of improvements in symptoms of anxiety, depression and psychological flexibility. The results of this study suggest that a larger-scale randomised controlled trial would be feasible to conduct and is warranted. Current Controlled Trials ISRCTN12268776. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 54. See the NIHR Journals Library website for further project information.

Practice nurse-supported weight self-management delivered within the national child immunisation programme for postnatal women: a feasibility cluster RCT

Pregnancy is a high-risk time for excessive weight gain. The rising prevalence of obesity in women, combined with excess weight gain during pregnancy, means that there are more women with obesity in the postnatal period. This can have adverse health consequences for women in later life and increases the health risks during subsequent pregnancies. The primary aim was to produce evidence of whether or not a Phase III trial of a brief weight management intervention, in which postnatal women are encouraged by practice nurses as part of the national child immunisation programme to self-monitor their weight and use an online weight management programme, is feasible and acceptable. The research involved a cluster randomised controlled feasibility trial and two semistructured interview studies with intervention participants and practice nurses who delivered the intervention. Trial data were collected at baseline and 3 months later. The interview studies took place after trial follow-up. The trial took place in Birmingham, UK. Twenty-eight postnatal women who were overweight/obese were recruited via Birmingham Women's Hospital or general practices. Nine intervention participants and seven nurses were interviewed. The intervention was delivered in the context of the national child immunisation programme. The intervention group were offered brief support that encouraged self-management of weight when they attended their practice to have their child immunised at 2, 3 and 4 months of age. The intervention involved the provision of motivation and support by nurses to encourage participants to make healthier lifestyle choices through self-monitoring of weight and signposting to an online weight management programme. The role of the nurse was to provide regular external accountability for weight loss. Women were asked to weigh themselves weekly and record this on a record card in their child's health record ('red book') or using the online programme. The behavioural goal was for women to lose 0.5-1 kg per week. The usual-care group received a healthy lifestyle leaflet. The primary outcome was the feasibility of a Phase III trial to test the effectiveness of the intervention, as assessed against three traffic-light stop-go criteria (recruitment, adherence to regular self-weighing and registration with an online weight management programme). The traffic-light criteria results were red for recruitment (28/80, 35% of target), amber for registration with the online weight loss programme (9/16, 56%) and green for adherence to weekly self-weighing (10/16, 63%). Nurses delivered the intervention with high fidelity. In the qualitative studies, participants indicated that the intervention was acceptable to them and they welcomed receiving support to lose weight at their child immunisation appointments. Although nurses raised some caveats to implementation, they felt that the intervention was easy to deliver and that it would motivate postnatal women to lose weight. Fewer participants were recruited than planned. Although women and practice nurses responded well to the intervention and adherence to self-weighing was high, recruitment was challenging and there is scope to improve engagement with the intervention. Future research should focus on investigating other methods of recruitment and, thereafter, testing the effectiveness of the intervention. Current Controlled Trials ISRCTN12209332. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 49. See the NIHR Journals Library website for further project information.