Technology advances have resulted in cheaper and quicker genomic sequencing (panels, exomes, whole genomes). Uptake into clinical practice has been rapid despite limited consideration of workforce, patient safety, consent, practice standards, guidelines and cost benefit. AUD 150M (USD 113M) has been independently allocated to genomic initiatives by Australian state and federal governments that don't reflect a national approach to genomics.

Modified horizon scanning (HS) methodology identified issues around genomic sequencing to be considered by governments regarding their support, or otherwise, before appropriate implementation and diffusion into local healthcare systems. A national jurisdictional advisory group was subsequently established that undertook extensive stakeholder consultation across Australia, including written submissions, over a four-month period.

HS identified that genomic sequencing is diffusing rapidly through the health system and flagged issues of pressing concern, including: workforce requirements; education, training and literacy for the medical workforce and community; infrastructure; data; and ethical, legal and social implications (ELSI). HealthPACT recommended a national coordinated approach to policy development across jurisdictional boundaries to ensure appropriate adoption of genomics. Stakeholder consultation confirmed overwhelming support for greater national coordination of the application of genomic knowledge in healthcare. Five strategic priorities were developed to support appropriate integration of genomics into health care for Australians: person-centered approach; workforce; financing; services; and, data. Three principles underpin strategic priorities: i) application of genomic knowledge is ethically, legally and socially responsible and community trust is promoted; ii) access and equity are promoted for vulnerable populations; and, iii) application of genomic knowledge to health care is supported and informed by evidence and research.

HS identified significant policy, workforce, funding and sustainability issues already facing state and territory governments that would, in time, face the federal government. The National Health Genomics Policy Framework outlines an agreed high-level national approach to policy, regulatory and investment decision-making for genomics and was approved by all Australian health Ministers in November 2017.

Tumor profiling tests can help to identify whether women with breast cancer need chemotherapy due to their risk of relapse, and some may be able to predict benefit from chemotherapy. We focused on four genetic tests: Oncotype DX (O-DX), MammaPrint (MMP), EndoPredict and Prosigna, and one immunohistochemistry test, IHC4, for the National Institute of Health and Care Excellence as part of their Diagnostic Appraisal Programme.

A systematic review was undertaken, including searching of nine databases in February 2017 plus other sources including a previous review published in 2013. The review included studies assessing clinical effectiveness of the five tumor profiling tests, with or without clinicopathological factors, to guide decisions about adjuvant chemotherapy in people with ER-positive, HER-2 negative, Stage I-II cancer with 0 to 3 positive lymph nodes (LN). The PROBAST tool and Cochrane risk of bias tools were used to assess risk of bias.

A total of 153 studies were included; the strength of evidence base for individual tests was varied. Results suggest all tests are prognostic for risk of relapse, though results were more varied in LN positive (+) patients than in LN negative (0) patients. Evidence was limited about whether tests can predict benefit from chemotherapy (available for MMP and O-DX only). Studies that assessed the impact of the tests on clinical decisions indicate that the net change in chemotherapy recommendations or decisions pre-/post-test ranged from an increase of one percent to a decrease of 23 percent among UK studies, and a decrease of zero percent to 64 percent across European studies.

The studies included in the review suggest that all of the tests can provide prognostic information on the risk of relapse; however results were more varied in LN+ patients than in LN0 patients. There is limited and varying evidence for prediction of chemotherapy benefit.

Methods that accommodate heterogeneity in outcomes are not widely used in economic evaluation. With the growth of precision medicine (PM), where choice of treatment is informed by the molecular characteristics of the patient or disease, we expect to see greater heterogeneity in effectiveness and cost of interventions. Our objective was to compare analytical frameworks for valuing heterogeneity in economic evaluation, and consider their strengths and weaknesses for applications in PM.

We conducted a literature review to identify papers that proposed an analytical framework for economic evaluation of a health intervention, and that placed a value on heterogeneous effects. We compared the frameworks considering the purpose of the analysis, including where in the product lifecycle the framework could be used, the types of PM interventions where the framework could be applied, and its ability to address methodological challenges of evaluating PM.

Five analytical frameworks were identified: covariate adjustment methods, value of stratification, value of heterogeneity (VoH), expected value of individualized care (EVIC), and loss with respect to efficient diffusion (LED) metrics. Each framework addresses a slightly different research question, and is suited to different settings and interventions. With the exception of covariate adjustment, all focus on maximizing net benefit within certain constraints and quantify the opportunity cost of ignoring heterogeneity. Only VoH considers the relationship between heterogeneity and uncertainty, and no framework explicitly includes the cost or uncertainty associated with identifying subgroups.

The ability to value heterogeneity is a critical component of economic evaluations of PM. The choice of an appropriate analytical framework will help strengthen the quality of economic evidence available to support health technology assessment of PM technologies, informing PM adoption decisions, and supporting efficient allocation of health care resources.

To facilitate moving from research findings to conclusions when conducting systematic reviews (SRs) and health technology assessments (HTAs), evidence grading systems (EGSs) have been developed to assess the quality of bodies of evidence and communicate (un)certainty about the effects of evaluated technologies. Use of EGSs has become an essential step in conducting SRs and HTAs and those relying on review conclusions should be aware of EGSs’ potential limitations.

This study aims to identify EGSs used in SR and HTA practice, and summarize findings on their inter-rater reliability (IRR). Relevant sources were searched to identify EGSs used in recently published SRs and IRR studies of available EGSs. Members of the International Network of Agencies for Health Technology Assessment were surveyed regarding their current approaches.

Preliminary results indicate that only two conceptually similar EGSs are currently used by several organizations in SR and HTA practice: (i) the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and (ii) the Agency for Healthcare Research and Quality Evidence-based Practice Center Program (AHRQ-EPC). Both approaches emphasize a structured and transparent method. However, results from published IRR studies suggest there is a risk for variability in their application due to researchers’ diverse levels of training and experience in using them, and the complexity and heterogeneity of evidence in SRs.

Validated EGSs can play a critical role in whether and how research findings are eventually translated into practice. However, our results indicate a low level of uptake of EGSs in HTA practice. Both currently used EGSs are susceptible to misuse that allows different researchers to grade the same body of evidence differently, and their performance has not been robustly explored in terms of IRR. If these results stand up to replication, one cannot rely on conclusions of published SRs, which has implications for the decisions they inform.

Although individual patient data meta-analysis (IPD MA) is considered the gold standard of systematic reviews (SRs), a recent International Network of Agencies for Health Technology Assessment survey indicates that IPD MA is not frequently included in a health technology assessment (HTA), or conducted by HTA researchers. The objective of this presentation is to describe our first experience with including an IPD MA in a HTA report, discuss the added value for an evidence-based decision-making process, and advocate for expanding work in this field.

An overview of SRs on endovascular therapy for acute ischemic stroke included one IPD MA and six study-level SRs/MAs. Methodological quality was appraised by two reviewers independently using the tool recommended by the Cochrane IPD MA working group for the IPD MA, and the AMSTAR (A MeaSurement Tool to Assess systematic Reviews) for the study-level reviews. Pooled results from subgroup analyses based on access to primary patient data were compared to those reported in SRs that conducted subgroup analyses based on the published data to identify patients or clinical factors that would impact clinical outcomes.

The overall findings were similar between the IPD MA and other SRs/MAs. However, when compared to aggregated data used in study-level SRs/MAs, subgroup analyses based on patient data allowed for adjustment of confounders, multiple categories within a subgroup, standardization of outcomes across trials, and detailed data checking. Larger sample sizes of each pre-defined subgroup permitted for more precise estimates of treatment effects. A number of methodological issues in the IPD MA were identified; particularly, no assessment of risk of bias of included trials was conducted.

Access to original patient data is demanding and conducting IPD MA requires extensive resources. The advantages of having an improved quality analysis, an appropriate quantification of the effects in the analyzed subgroups, and precision of results may justify additional efforts, and may increase confidence in the decision-making process.

Novel health technologies are being developed at a dizzying pace. The need to avoid unnecessary innovations and accelerate the adoption of valuable innovations is among the most important challenges facing healthcare systems today. To contribute to this challenge, we performed 30 so-called ‘early health technology assessments’ (HTA) over the last three years. We quantified the potential value, both in effects and cost. We will present our experience with performing these constructive assessments, as well as their feasibility and value in informing decisions.

We performed secondary analyses on an existing database of 30 assessments. We analyzed the phase of development, stakeholders involved, type of decision informed, and the technology's next steps.

Out of the 30 technologies, four (13 percent) were in the idea screening phase, and had not yet started the development. Here, the room for improvement (headroom) was assessed. For 16 (53 percent) technologies that were under development but not yet studied, we performed headroom and threshold analyses. For the 10 (33 percent) developed technologies where some (pilot) data were already available, scenario and/or cost-effectiveness analyses were performed. The assessments, that were commissioned by developers, clinicians or hospital managers informed evidence-based decisions on (further) development, focus, research design or adoption in clinical practice. Preliminary results suggest that after the assessment, decisions were made to stop further development (n=2), continue outside healthcare (n=1), change the target population (n=3) or change the proposed positioning in the care pathway and/or value proposition (n=4).

Stakeholders deemed an early, formative assessment useful in informing development, research and adoption decisions, in different stages of development. Even before developing a technology, headroom analyses appeared to be feasible and useful. Consequences of the assessments mostly related to a shift in focus, which may result in more efficient research and development, as well as more valuable innovations.

Commissioners of systematic reviews have differing requirements in terms of breadth of scope, level of analysis required, and timescales available. Planning a review requires consideration of the trade-off between these elements. This applies to both “rapid” reviews and “traditional” reviews with a broad or complex scope.

Approaches for tailoring review methods to commissioner requirements are described. These will be illustrated via case studies of reviews conducted for the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) and Health Services & Delivery Research (HS&DR) programs and other organizations.

An initial step is to discuss with commissioners the trade-off between timescales/resource available, breadth of review scope, and level of analysis; for example, broad overview of many studies or in-depth analysis of a narrower set. Where the evidence base is unknown, one option is to undertake an initial mapping review to assess the volume and type of evidence available. This may assist in refining the selection criteria for the main review, to prioritize the most relevant evidence. In complex reviews, a further option is to develop a conceptual model (logic model) with input from commissioners and experts, to help identify factors which may influence outcomes. This can enable design of focused mini-reviews (not necessarily exhaustive) around each factor. These methodological approaches will be illustrated through three case studies including an HTA on cannabis cessation (trade-off of breadth versus depth); a review of yoga and health (initial mapping to refine selection criteria); and a rapid review of congenital heart disease services (conceptual model to identify areas for focused reviews).

Different approaches may enable discussion with review commissioners around the trade-off between scope, methods and timescales, in order to tailor the review method to best meet commissioner requirements within the timescales available.

The Health Technology Assessment (HTA) Program at the Institute of Health Economics (IHE) has conducted rapid assessments (RAs) for 25 years. The presentation draws on this experience to chart the evolution of RAs over a 25-year relationship between a policy maker and an arms-length HTA agency to quantify the effects of this partnership on the RAs produced.

The number, types, and methodological attributes of RAs produced over a 25-year partnership with a single requestor were reviewed. The reasons for developmental changes in RA products over time were charted to document the push-pull tension between requestor needs and HTA best practice. The elements contributing to the relevance and impact, or not, of the RAs were also identified.

Results demonstrated the dynamic relationship required for HTA researchers to meet best practice and requestor needs. As literature search spans lengthened and data analyses became more complex, limitations were imposed on RAs to fulfill the requirements of timeliness, utility, and best practice. Adaptations were driven by requestor, researcher, and the external policy environment. Facilitators of RA utility for HTA requestors include: asking focused, well-articulated questions; specifying the request's purpose; providing detailed information about local context and other relevant issues; and understanding the risk of bias associated with RAs. Considerations for HTA doers include: assembling a team using a triage process; involving requestors throughout RA development; negotiating deliverables and timelines using a HTA product matrix; transparently reporting methods; narratively describing methodological issues; and internally reviewing the draft RAs.

RAs are a useful component of HTA programs. To keep these products relevant and useful, HTA agencies must allow RAs to evolve according to need, but with grounding in good practice. Negotiating the line between rigor and relevance is a key skill for HTA agencies. Having the right team is helpful.

Ethics is a set of moral principles that guide our behavior when it affects others. HTAi acknowledges the fundamental values of “service, collaboration, professionalism and integrity, transparency, accountability”. Ethical conduct balances self-interest with consequences of that behavior for others. Unethical behavior has serious personal consequences and in the case of HTA practitioners it can damage stakeholder trust and thereby hinder implementation of evidence by policy makers. Compliance with regulation alone may not suffice in building stakeholder confidence. There is need for individuals and agencies to develop a ‘culture of integrity’ at all levels in the HTA process above and beyond compliance with the law. A strong ethical culture will foster trust of stakeholders, strengthen collaboration, improve implementation of recommendations and benefit society. This is the importance of developing a code of ethics to guide conduct and detail standards of professional practice expected of HTA practitioners affiliated to HTAi and related agencies.

I will argue for the development of a detailed code of ethics for HTAi and related agencies. To do this, I will explain how the code of ethics gives guidance and informs the users (HTA practitioners), and how they can guide stakeholders in the HTA processes. The public relations benefits of a code of ethics will also be discussed. I will explain why having a mere list of seven words as “values” is not sufficient guidance to professionals with diverse backgrounds who are collaborating in a multidisciplinary team.

The role of a code of ethics in helping professionals to choose their actions well is an effective way to integrate ethics in HTA, safeguard the integrity of HTA processes, and improve evidence implementation by stakeholders.

HTAi should develop a detailed code of ethics for its membership.

Recent equity review guidance encourages reviewers to consider whether it is likely that their findings may impact on health inequalities. Much of the guidance assumes that health inequalities have either already been identified as the focus of the review, or that reviewers are able to recognize if and how health inequalities matter. However, our experience is that this is not necessarily true. Furthermore, theorizing if and how health inequalities matter is not normally integrated into the HTA review process. This presentation describes a novel approach to the development of a theory-led meta-framework to inform health inequality considerations in systematic reviews. The meta-framework aims to increase the usefulness of systematic reviews in informing and implementing changes to practice.

Following the best-fit framework synthesis approach, a meta-framework was generated by ‘deconstituting’ concepts from theories relating to complex interventions and socio-economic health inequalities into a single framework. Feedback was sought from health inequality experts and reviewers.

Complex intervention theories identify four domains and key factors that may influence effectiveness; intervention design, implementation, context and participant response. Applying an equity lens, socio-economic health inequality theories identify key factors and mechanisms associated with these domains that may lead to differential effects across disadvantaged populations.

The meta-framework has the potential to i) facilitate the identification and understanding of when, why and how interventions may impact on socio-economic health inequalities, ii) promote a theory-led approach to incorporating health inequalities in systematic reviews iii) help reviewers identify data to extract and inform a priori analysis on what factors are associated with differential effects, iv) help reviewers to decide whether it is likely that their review findings may have the potential for an intervention to indirectly widen or narrow socio-economic health inequalities, even when evidence of an impact in the primary research is lacking.

Different disciplinary frameworks in the field of Health Technology Assessment (HTA) may hold different, and potentially contradictory, assumptions about a technology's value or optimal use. For example, economic analyses may be based on outcome measures that are socially controversial or ethically problematic. This can result in economic and ethical evaluations that are difficult to reconcile, leaving HTA short of its goal to provide policy decision-makers with a holistic assessment of technology. We use the case of non-invasive prenatal testing (NIPT) to explore whether the capabilities approach can be used to align economic and ethical concepts of value in assessments of morally challenging health technologies. The capabilities approach is an economic framework which bases wellbeing assessments on a person's abilities, rather than their expressed preferences.

To develop concepts for capabilities relevant to NIPT, we started with Nussbaum's capabilities framework, and conducted a directed qualitative content analysis of interview data from twenty-seven Canadian women with personal experience of this technology.

We found that eight of Nussbaum's ten capabilities related to options or choices that women valued in the context of NIPT, and identified one new capability, Care Taking. NIPT has a meaningful impact on women's capabilities, and capabilities concepts can capture the value of NIPT without relying on health outcomes of ambiguous social and ethical value. A capabilities approach may help reconcile ethical and economic value frameworks for NIPT.

The capabilities approach can contribute to economic evaluations of morally challenging health technologies that better reflect patient preferences and ethical concerns, and may contribute to more holistic HTAs. It provides a framework within which policy analysts from diverse disciplines can communicate about the social and ethical value of morally challenging health technologies. Future research should focus on operationalizing the capabilities approach for use in evaluations of NIPT and other morally challenging health technologies.

It is widely recognized that the incorporation of patient and public perspectives can enrich health policy decision-making. Methodological and practical advice on engaging patients and the public has proliferated in recent years, with many health technology assessment (HTA) agencies working to formalize their processes in this area. However, despite growing enthusiasm for patient and public engagement, many ethical issues remain unaddressed including: balancing risks and benefits to participants; recruitment methods; reimbursement for time spent participating; representation; and, information disclosure.

In this critical analysis, we draw on our collective experiences engaging with patients and public in the context of HTA. We use principles from two theories, i) research ethics, and ii) participatory governance, to analyze these challenges. The purpose of this analysis is to explore the ways in which risks and benefits to patient and public participants might be balanced in HTA activities.

We begin by describing some ethically challenging experiences we have faced when soliciting views and values from patients and members of the public, some anticipated and some unexpected. These challenges include unexpected disclosures of information, navigating power differentials when working with vulnerable populations, eliciting information about potentially traumatizing experiences, and fairly representing controversial and conflicting opinions. We offer examples about what types of patient engagement activities may subject participants to unreasonable risk, and suggest some guiding principles to help plan ethical patient and public engagement activities.

Patient and public engagement requires more than just procedural methodological expertise- it also requires the ability to identify and analyze relevant ethical issues. We posit that health technology assessors have a moral obligation to ensure that the risks of patient and public engagement activities do not outweigh the benefits. We call upon the HTA community to engage in thoughtful deliberation about what can be learned from experiences within HTA and in other contexts.

While methods for ethics analysis in health technology assessment (HTA) exist, there have been relatively few applications and assessments of these methods. The Canadian Agency for Drugs and Technologies in Health (CADTH) began to include an explicit analysis of ethical issues within its HTAs in 2015. To examine some of the differences among ethics analyses, we critically compared the conduct and contribution of the analysis of ethical issues for four CADTH HTAs.

Two experts in ethics in HTA examined ethics analyses conducted by CADTH for four technologies: DNA mismatch repair testing for colorectal cancer, treatments for obstructive sleep apnea, dialysis for end-stage liver disease, and human papillomavirus screening for cervical cancer. The methods of analysis and presentation of results, extent to which the ethics analysis was used in committee deliberations was gathered via meeting notes, recommendation documents, and discussion, and were summarized narratively.

The amount of literature explicitly discussing ethical issues pertaining to particular technologies varied and was not predicted by the age and maturity of a technology. The axiological approach proved a helpful starting point for ethical reflection, but other methods were used for analysis and presentation. Explicit discussion of ethical issues identified the need for additional information to ensure robust deliberation. Committee members expressed the belief that ethics analysis “brought together” individual sections of the HTA.

While many methods exist for ethics analysis, ethics expertise is required to identify and explicitly discuss the complete range of ethical issues relevant to a particular HTA. Ethics analyses create space to challenge assumptions underlying the clinical and economic evidence, raise issues about the value of technologies, and help to integrate the HTA results.

Management of new-onset diabetes is important to achieve metabolic stabilization, minimize acute complications, and to provide insulin therapy, diabetes education and psychological support. A health technology assessment (HTA) was conducted to determine if an outpatient setting could be effective and safe for new-onset diabetes in children, and how it can be implemented in our pediatric center.

A systematic search on initial management (outpatient versus in-hospital) of diabetes in children was performed in multiple databases and grey literature. Practice guidelines (CPGs), systematic reviews (SRs), randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs) published up to August 2017 were identified. Telephone interviews with key informants from two children's university teaching hospitals were performed to collect information on outpatient initial management models and issues related to their implementation. An interdisciplinary group of experts from our pediatric center collaborated in this project.

According to 5 CPGs, hospitalization would not be required for children without acute complications at time of diagnosis or after initial treatment of ketoacidosis if outpatient care facilities, resources, and education are available. Results from one SR and 7 NRCSs suggested that outpatient initial management is associated with good metabolic control (glycated hemoglobin) and is as safe as the inpatient care model, based on rate of hospital admissions, severe hypoglycemia, and ketoacidosis episode. However, few data regarding treatment adherence, knowledge acquisition, and emotional adaptation were identified. Outpatient education programs can be successfully provided on several consecutive or non-consecutive days after diagnosis as reported by two children's university teaching hospitals.

Although data on effectiveness and safety are scarce and of low-quality, outpatient management of newly diagnosed diabetes, uncomplicated or stabilized, is recommended in children. However, data on children and their families should be collected as part of the implementation evaluation in order to enhance its efficacy and the quality of the patients’ and families’ experiences.

Children who undergo short, painful procedures at hospitals are given different kinds of pain relief (analgesics), often in combination with drugs for relaxation (sedatives). Nitrous oxide (NO) is a drug administered for pain relief and relaxation, it is applied by inhalation and its effects are analgesic, anxiolytic and sedative. It is used in several countries, but is not normally used as a sedation method for children in Norwegian hospitals, although widely used in maternity wards during labor. Our aim was to evaluate the effectiveness and safety of this sedation regimen in children. However, we also wanted to assess safety for health personnel after repetitive or long-term exposure.

We performed a systematic review on effectiveness and safety of nitrous oxide for sedation in children. For evidence on efficacy and safety in children, only randomized controlled trials (RCT) were included. For safety of health personnel we also accepted other study designs. For all endpoints, we presented the evidence in summary of finding tables.

We retrieved twenty-two randomized controlled trials on the effectiveness or safety in children undergoing sedation with nitrous oxide. Outcomes were hospital procedure satisfaction or characteristics, and pain relief. Safety was reported as acute adverse events. None of the RCTs reported evidence on safety for health personnel. We are currently exploring different ways to systematically assess safety for health personnel within the form of an HTA otherwise designed for a different population.

Assessing safety of new technologies, methods or procedures through HTAs is a crucial point. However, assessing the long-term safety of the health personnel should also be included, but evidence will often not be retrieved through literature search designed for the patient group, and long-term safety data is in general difficult to retrieve for exposure to a novel technology. We will discuss our approach to this challenge.

Reduction of biologics after reaching low disease activity rheumatoid arthritis has been tested in clinical trials. The aim of this systematic review is to assess the effectiveness and safety of the reduction of biologics drugs in patients with rheumatoid arthritis in low disease activity.

The protocol of this review is registered at PROSPERO (CRD42017069080). We searched MEDLINE, Embase, Scopus and The Cochrane Library for randomized controlled trials that reduced or spaced the dose of biologics in patients at low disease activity or remission state compared with maintenance. Two researchers selected studies, extracted the data, and assessed the risk of bias of the studies. Random effects meta-analyses by DerSimonian & Laird method were calculated considering intention to treat analysis to obtain the standardized mean difference (SMD) or relative risk (RR) and 95 percent confidence interval (CI). Quality of evidence will be assessed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE).

From 725 retrieved records, seven studies were included. Compared to regular doses, reduction of biologics significantly increased the health assessment quality (SMD = 0.20; 95% CI: 0.04 0.37; I2 = 3.5%). No difference was observed for low disease activity (RR = 0.83; 95% CI: 0.68, 1.03; I2= 71.3), serious and non-serious adverse events; disease activity scores; patient global assessment and radiographic progression.

Preliminary results show no differences in clinically relevant outcomes from reduction of biologics compared to regular doses. As a limited number of studies is available, the certainty of evidence is limited and need to be monitored to better inform patients and clinicians.

Calling in staff and preparing the operating room for an urgent surgical procedure is a significant draw on hospital resources and disrupts care of other patients. It has been common practice to treat open fractures on an urgent basis. HTA methods can be applied to examine this prioritization of care, just like they can be applied to the acquisition of drugs and devices.

Our center completed a rapid systematic review of guidelines, systematic reviews, and primary clinical evidence, on urgent surgical debridement and stabilization of open fractures of long bones (“urgent” being defined as within six hours of the injury) compared to surgical debridement and reduction performed at a later time point. Meta-analyses were performed for infection and non-union outcomes and the GRADE system was used to assess the strength of evidence for each conclusion.

We found no published clinical guidelines for the urgency of treating open fractures. A good systematic review on the topic was published in 2012. We found six cohort studies published since completion of the earlier review. The summary odds ratio for any infection in patients with later treatment was 0.97 (95% confidence interval (CI) 0.78–1.22, sixteen studies, 3,615 patients) and for deep or “major” infections was 1.00 (95% CI 0.74–1.34, nine studies, 2,013 patients). The summary odds ratio of non-union with later treatment was 0.95 (95% CI 0.65–1.41, six studies, 1,308 patients). There was no significant heterogeneity in any of the results (I-squared = 0 percent) and no apparent trends in the results as a function of study size or publication date. We graded the strength of each of the conclusions as very low because they were based on cohort studies where the treating physician could elect immediate treatment for patients with severe soft-tissue injuries or patients at risk of complications. This raises the risk of spectrum bias.

Default urgent scheduling of patients with open fractures for surgical debridement and stabilization does not appear to reduce the risk of infection or fracture non-union. Based on this information, our surgery department managers no longer schedule patients with open fractures for immediate surgery unless there are specific circumstances necessitating it.

Traditional meta-analyses synthesize aggregate data obtained from study publications or study authors, such as a treatment effect estimate and its associated uncertainty. An increasingly important approach is the meta-analysis of individual participant data (IPD) where the raw individual-level data are obtained for each study and used for synthesis. This study compares and discusses results from an IPD meta-analysis vs standard meta-analysis of randomized controlled trials of exercise cardiac rehabilitation in chronic heart failure (CHF).

Based on a previous systematic review, the Exercise Training Meta-Analysis of Trials for Chronic Heart Failure (ExTraMATCH II) identified and collected IPD from randomized controlled trials (RCTs) that compared exercise rehabilitation with a non-exercise control with a minimum follow-up of six months. For this abstract, the outcome of interest was all-cause mortality. Original IPD were checked for consistency and compiled in a master dataset. Standard meta-analytic models were used for aggregate data whilst two-stage and one-stage approaches, accounting for the clustering of participants within studies, were planned for statistical analyses of IPD.

Overall thirty-three RCTs were included in the original systematic review, whereas within the ExTraMatch II project, IPD on all-cause mortality were obtained from seventeen RCTs of approximately 3,700 patients. From aggregate data there was no significant difference in pooled mortality (relative risk 0.92, 95% confidence interval 0.67 to 1.26). IPD analysis revealed 701 events across exercise and control groups. Our ongoing IPD analyses will allow us to examine how patients’ characteristics (e.g. age, New York Heart Association functional class, ejection fraction) modify treatment benefit.

Given the limitations of current trial level meta-analysis evidence in CHF, access to individual data from several RCTs offers a timely and important opportunity to revisit the question of which CHF patient subgroups benefit most from exercise-based rehabilitation.

North America is facing a public health epidemic – the opioid crisis – part of which is attributed to the inappropriate use of opioids in pain management. As such, the 2017 Canadian Guideline for Opioids for Chronic Non-Cancer Pain recommends optimizing non-opioid pharmacotherapy or non-pharmacological therapy to treat chronic pain, before a trial of opioids. However, the Guideline itself is not designed to provide evidence on the effectiveness of these non-opioid alternatives, leaving a gap for those attempting to put the recommendation into practice.

In collaboration with its partners, including clinicians and policymakers, the Canadian Agency for Drugs and Technologies (CADTH) identified the gaps in evidence, and developed an action plan to bridge the evidence gaps to support the optimization of non-opioid alternatives in pain management.

Since the release of the Guideline, CADTH produced over 20 Rapid Response reports that synthesize and appraise evidence on non-opioid alternatives in the management of a wide range of pain, both acute and chronic. Additionally, CADTH has also reviewed evidence on multidisciplinary pain treatment programs, and is developing environmental scan reports on the availability and access to non-pharmacological treatments for pain in Canada, and on drugs for emerging non-opioid pain. Further, CADTH developed knowledge mobilization tools based on the evidence reviews. The evidence reviews and tools are used as a resource by CADTH partners, including the Coalition of Safe and Effective Pain Management and McMaster University National Pain Center.

This presentation will discuss the role of HTA and CADTH to fill the gaps in evidence for a crucial clinical practice guideline recommendation in a time of public health crisis, and help put the evidence into action. It will present the evidence synthesized by CADTH on various non-opioid alternatives for pain management, while highlighting the remaining gaps in evidence. Understanding the evidence on non-opioid alternatives will inform clinical and policy decisions and potentially reduce inappropriate use of opioids in pain management.

Over the past decade, health technology assessment (HTA) agencies have become interested in improving the patient-centeredness of their assessments. A common approach has been to prioritize patient-reported outcomes (PROs), often describing PROs as patient-relevant or patient-oriented. However, it is often unclear whether and to what degree PRO measures (PROMs) truly reflect what is important to patients. This review examined the pedigree of a sample of measures used as primary or secondary endpoints in trials and discussed in Food and Drug Administration (FDA) approved product labels between 2003 and 2014.

We examined all 26 PROs included in chapters 1 (Office of Microbial Products) and 2 (Office of Drug Evaluation I) of the FDA's Pilot Clinical Outcome Assessment (COA) Compendium. Three reviewers independently searched PubMed and Google to identify publications or other relevant materials related to method and stage of measure development where patient engagement took place.

Among 26 evaluated PROMs, we were unable to locate any information on development or validation for 12 (patient diary=9; rating scale=3). Among the remaining 14 PROMs, 5 did not include any evidence of patient engagement (questionnaire=1; patient diary=2; rating scale=2); 3 engaged patients during concept elicitation or psychometric validation only (disease-specific questionnaires=3); and 6 engaged patients during both concept elicitation and cognitive interviewing (disease-specific questionnaires=6). PROMs either previously qualified or submitted for qualification by FDA were more likely to include patient engagement.

PROs can provide patient-centered data useful for HTA; however, patient-reported information is not inherently patient-centered. This study found that only a minority of sampled PROMs engaged patients during both concept elicitation and cognitive interviewing. To facilitate patient-centered HTA, manufacturers should ensure that PROMs incorporated into clinical trials measure concepts important to patients. Similarly, HTAs should request data on development and validation of all outcome measures incorporated into trials.