Objectives: Health technology assessment (HTA) has to innovate to best support changing health system environments and to help provide access to valuable innovation under fiscal constraint.

Methods: Issues associated with changing HTA paradigms were identified through scoping and explored through deliberation at a meeting of industry and HTA leaders.

Results: Five broad areas of change (engagement, scientific dialogue, research prioritization, adaptive approaches, and real world data) were identified. The meeting focused on two themes derived from these: re-thinking scientific dialogue and multi-stakeholder engagement, and re-thinking value, affordability, and access. Earlier and ongoing engagement to steer the innovation process and help achieve appropriate use across the technology lifecycle was perceived as important but would be resource intensive and would require priority setting. Patients need to be involved throughout, and particularly at the early stages. Further discussion is needed on the type of body best suited to convening the dialogue required. There was agreement that HTA must continue to assess value, but views differed on the role that HTA should play in assessing affordability and on appropriate responses to challenges around affordability. Enhanced horizon scanning could play an important role in preparing for significant future investments.

Conclusions: Early and ongoing multi-stakeholder engagement and revisiting approaches to valuing innovation are required. Questions remain as to the most appropriate role for HTA bodies. Changing HTA paradigms extend HTA's traditional remit of being responsive to decision-makers demands to being more proactive and considering whole system value.

Objectives: Made available since 2002, transcatheter aortic valve implantation (TAVI) is a minimally invasive new intervention which can provide significant survival improvement to patients with aortic stenosis. However, TAVI is expensive and currently not reimbursed by many governments. Some governments and institutions have been conducting health technology assessments (HTAs) to inform their reimbursement decisions. The aim of the present study is to review HTAs that have relied on a cost-effectiveness analysis to inform reimbursement decisions of TAVI.

Methods: A systematic literature review was conducted among published literature as well as reports released by HTA agencies. Predetermined inclusion and exclusion criteria, following the Preferred Reporting System for Systematic Reviews and Meta-Analysis guidelines, were used to select relevant HTAs. The selected papers were assessed against the Consolidated Health Economic Evaluation Reporting Standards.

Results: HTAs on TAVI from three countries were available for this review: Canada, Belgium, and the United Kingdom. All three HTAs used the Placement of Aortic Transcatheter Valve (PARTNER) trial data with Markov models to estimate the incremental cost effectiveness ratio. The three HTAs recommended conditional reimbursement for TAVI for otherwise inoperable patients. The HTAs did not use clear methods to estimate the health-related utility which ultimately affected their cost-effectiveness results. The UK HTA showed the best value for money (US$20,416 per quality-adjusted life-year).

Conclusion: All studies found TAVI to be more costly and less effective for high-risk patients suitable for surgery, whereas TAVI was consistently found to be cost effective for otherwise inoperable patients.

The Special Interest Group on Ethics and HTA (health technology assessment) has invited two renowned philosophers, Norman Daniels from Harvard University and Henry Richardson from Georgetown University to reflect on the role of HTA in healthcare policy making. Both acknowledge its importance, but at the same time warn against a too mechanistic deployment of HTA. In their view, the relevance of HTA to healthcare policy making would considerably be enhanced if it were subsumed within a broader deliberative framework. Why should this be so? What is there to deliberate on, who should do the deliberating, where and when, and how does this relate to the more technical elements of HTA such as evidence synthesis and economic modeling?

Objectives: Companion diagnostic tests (CDx) are used to measure an individual's protein or gene expression (biomarkers) to inform choice of therapy. The increasing number of drugs requiring CDx poses challenges for regulatory and reimbursement policies. To better understand this issue, an environmental scan was conducted by the Canadian Agency for Drugs and Technologies in Health (CADTH).

Methods: The environmental scan was based on a focused literature search and feedback solicited from targeted stakeholders.

Results: The global market for CDx is expected to grow considerably until the end of this decade, with compound annual growth rate around 20 percent. Several factors may impact the adoption of CDx, including the potential cost-savings associated with reduced treatment failures and adverse reactions. Anticipating an expansion in drugs with CDx, some countries have updated their regulatory frameworks, including the United States where the FDA released new guidance in 2014. With respect to reimbursement, both the United Kingdom and Australia updated their evaluation frameworks to inform reimbursement decisions; however, several countries, including Canada, have not published policies for co-dependent technology.

Conclusion: The market size for CDx is expected to considerably expand in the future. The drive in uptake may be influenced by many factors including an increased knowledge of biomarkers and molecular drivers of disease and the potential cost-savings associated with fewer treatment failures and adverse reactions. Assessing whether such benefits materialize is important. Health technology assessment will play an important role in informing policies regarding the clinical use and funding of pharmaceuticals with CDx.

Objectives: Various minimal clinically important difference (MCID) threshold estimation techniques have been applied to seasonal allergic rhinitis (SAR). The objectives of this study are to (i) assess the difference in magnitude of alternative SAR MCID threshold estimates and (ii) evaluate the impact of alternative MCID estimates on health technology assessment (HTA).

Methods: Data describing change from baseline of the reflective Total Nasal Symptom Score (rTNSS) for four intranasal SAR treatments were obtained from United States Food and Drug Administration-approved prescribing information. Treatment effects were then compared with anchor-based MCID thresholds derived by Barnes et al. and thresholds obtained from an Agency for Healthcare Research and Quality (AHRQ) panel.

Results: The change in rTNSS score from baseline, represented as the average of the twice-daily recorded scores of the rTNSS, was -2.1 (p < .001) for azelastine hydrochloride 0.10%, 1.35 (p = .014) for ciclesonide, and -1.47 (p < .001) for fluticasone furoate. The change in the rTNSS score from baseline, represented by sum of the AM and PM score, was -2.7 for MP-AzeFlu (p < .001). The rTNSS change from baseline for each product was compared with anchor-based MCID threshold and the AHRQ panel estimates. Comparison of the observed treatment effect to the anchor-based and AHRQ panel MCID thresholds results in different conclusions, with clinically important differences being inferred when anchor-based estimates serve as the reference point.

Conclusion: The AHRQ panel MCID threshold for the rTNSS was twelve times larger than the anchor-based estimates resulting in conflicting recommendations on whether different SAR treatments provide clinically meaningful benefit.

Objectives: The objectives of this study were to identify and qualitatively describe, in a systematic literature review, published studies that collected prostate cancer patients’ health-related quality of life (HRQoL) estimates by using validated, generic instruments.

Methods: Systematic searches of the literature were made using the Medline, Cochrane Library, PsycINFO, and CINAHL electronic databases from 2002 to 2015.

Results: The search identified 2,171 references, of which 237 were obtained for full-text assessment; thirty-three of these articles were deemed relevant and included in the systematic review. An indirect valuation method was used in 73 percent (n = 24) of the studies. The most commonly used HRQoL instrument with an indirect valuation method was the EuroQol (EQ-5D; n = 21), and the second most common was the 15D (n = 5). A direct valuation method was used in 48 percent (n = 16) of the studies. Of these, the Visual Analogue Scale (VAS) was the most often used (n = 10), followed by the Time-Trade-Off (n = 6). HRQoL scores varied in localized and early stage disease between 0.63 and 0.91, and in advanced or metastatic disease stage between 0.50 and 0.87. There was also variance in the HRQoL instruments and study methods used, which explains the large variance in HRQoL scores between the various disease stages.

Conclusions: Although utility and quality-adjusted life-years gained are considered important measures of effectiveness in health care, the number of studies in which utilities of prostate cancer patients have been estimated using generic HRQoL instruments, based on either direct or indirect measurement of HRQoL, is fairly small.

The need to progress and innovate in health technology assessment (HTA) is a must in a continuously changing environment. The HTAi Policy Forum reflected on two specific areas for development where it was thought there was need for careful consideration and deliberation during the main annual meeting in February 2016. The study by Husereau et al. (1) in this journal presents the discussions resulting from this Forum. To further share the deliberations of the Forum and with a view to opening this debate to the wider HTA community, a panel session during the HTAi Annual Meeting in Tokyo was organized. Presentations at the panel included a summary of the HTAi Policy Forum discussions and perspectives from a patient, a representative of healthcare system provider, and a representative from an HTA organization and industry. This letter presents the issues raised in the panel session.

Current thinking about the methodology of health technology assessment (HTA) seems to be dominated by two fundamental tensions: [1] between maintaining a tight focus on quality-adjusted life-years and broadening its concern out to pay attention to a broader range of factors, and [2] between thinking of the evaluative dimensions that matter as being objectively important factors or as ones that are ultimately of merely subjective importance. In this study, I will argue that health is a tremendously important all-purpose means to enjoying basic human capabilities, but a mere means, and not an end. The ends to which health is a means are manifold, requiring all those engaged in policy making to exercise intelligence in a continuing effort to identify them and to think through how they interrelate. Retreating to the subjective here would be at odds with the basic idea of HTA, which is to focus on certain objectively describable dimensions of what matters about health and to collect empirical evidence rigorously bearing on what produces improvements along those dimensions. To proceed intelligently in doing HTA, it is important to stay open to reframing and refashioning the ends we take to apply to that arena. The only way for that to happen, as an exercise of public, democratic policy making, is for the difficult value questions that arise when ends clash not to be buried in subjective preference information, but to be front-and-center in the analysis.

Objectives: The aim of this study was to obtain information on methods used to measure health technology assessment (HTA) influence, decisions that were influenced, and outcomes linked to HTA.

Methods: Electronic databases were used to locate studies in which HTA influence had been demonstrated. Inclusion criteria were studies that reliably reported consideration by decision makers of HTA findings; comparative studies of technology use before and after HTA; and details of changes in policy, health outcomes, or research that could be credibly linked to an HTA.

Results: Fifty-one studies were selected for review. Settings were national (24), regional (12), both national and regional (3) hospitals (9), and multinational (3). The most common approach to appraisal of influence was review of policy or administrative decisions following HTA recommendations (51 percent). Eighteen studies (35 percent) reported interview or survey findings, thirteen (26 percent) reviewed administrative data, and six considered the influence of primary studies. Of 142 decisions informed by HTA, the most common types were on routine clinical practice (67 percent of studies), coverage (63 percent), and program operation (37 percent). The most frequent indications of HTA influence were on decisions related to resource allocation (59 percent), change in practice pattern (31 percent), and incorporation of HTA details in reference material (18 percent). Few publications assessed the contribution of HTA to changing patient outcomes.

Conclusions: The literature on HTA influence remains limited, with little on longer term effects on practice and outcomes. The reviewed publications indicated how HTA is being used in different settings and approaches to measuring its influence that might be more widely applied, such as surveys and monitoring administrative data.

Objectives: This article presents a cost-utility analysis from the Colombian health system perspective comparing primary prophylaxis to on-demand treatment using exogenous clotting factor VIII (FVIII) for patients with severe hemophilia type A.

Methods: We developed a Markov model to estimate expected costs and outcomes (measured as quality-adjusted life-years, QALYs) for each strategy. Transition probabilities were estimated using published studies; utility weights were obtained from a sample of Colombian patients with hemophilia and costs were gathered using local data. Both deterministic and probabilistic sensitivity analysis were performed to assess the robustness of results.

Results: The additional cost per QALY gained of primary prophylaxis compared with on-demand treatment was 105,081,022 Colombian pesos (COP) (55,204 USD), and thus not considered cost-effective according to a threshold of up to three times the current Colombian gross domestic product (GDP) per-capita. When primary prophylaxis was provided throughout life using recombinant FVIII (rFVIII), which is much costlier than FVIII, the additional cost per QALY gained reached 174,159,553 COP (91,494 USD).

Conclusions: using a decision rule of up to three times the Colombian GDP per capita, primary prophylaxis (with either FVIII or rFVIII) would not be considered as cost-effective in this country. However, a final decision on providing or preventing patients from primary prophylaxis as a gold standard of care for severe hemophilia type A should also consider broader criteria than the incremental cost-effectiveness ratio results itself. Only a price reduction of exogenous FVIII of 50 percent or more would make primary prophylaxis cost-effective in this context.

Objectives: The study evaluates the costs of systemic lupus erythematosus (SLE) and the budget impact due to the introduction of belimumab in the Italian setting.

Methods: Adaptation to the Italian setting of a budget impact model with a time horizon of 4 years (year 0 without belimumab, years 1–3 with belimumab) to compare treatment, administration, and clinical monitoring costs of standard therapy and of the alternative scenario in which belimumab is administered in addition to the standard therapy to the subgroup of patients selected according to the label approved by the European Medicines Agency. The model takes also into account the costs of flares.

Results: Over 3 years, belimumab is able to prevent cumulatively 1,111 severe flares and 3,631 nonsevere flares with a total saving for the Italian National Health System (NHS) of approximately €6.2 million. Budget impact ranges from €4.4 million in the first year to €20.3 million in the third year.

Conclusions: The decrease in the number of flare partially counterbalances the costs of the new technology (impact attenuation of approximately 16 percent). These data elucidate the importance to control and monitor the disease progression and to prevent exacerbations, which are the major causes of the increase in costs paid by the NHS and by the society. The financial impact could be replicate on a regional basis, to inform local decision makers. Further developments are possible as the model does not consider the additional clinical and economic benefits of reduced damage accrual and slowed disease progression.

Background: Despite the cost of pharmaceuticals, studies assessing prices of osteoporosis drugs are lacking. This study examined trends in prices of osteoporosis drugs in the United States in the period 1988–2014, assessed pricing structure of osteoporosis drugs, and evaluated price trends before and after generic drugs market entry.

Methods: Data were derived from the U.S. Food and Drug Administration, the RedBook, the Centers for Medicare & Medicaid Services, and the Federal Supply Schedule (FSS). Descriptive statistics and segmented linear regression analyses were performed.

Results: In the period 1988–2014, osteoporosis drug prices increased faster than the inflation. The average wholesale price (AWP) of generic products at market entry represented 90 percent of the AWP for the corresponding brand. Prices of brand products continued to increase after generic entry. Drug prices showed a significant variation when compared with the brand AWP. The brand wholesale acquisition cost (WAC) was typically set at 83.3 percent of the AWP. Community pharmacies acquired osteoporosis brand drugs at a median of 80.5 percent of the brand AWP. Significant reductions in brand AWP were observed for Medicare Part B (78.5 percent of the brand AWP), generic National Average Drug Acquisition Cost (33.7 percent), and FSS (22.5 percent).

Conclusions: There are significant differences in the manufacturer prices, pharmacy acquisition costs and reimbursement rates of osteoporosis drugs. Pharmaceutical companies listed prices are higher than the pharmacy actual estimated acquisitions costs, and the prices used for reimbursement to providers. Generic drugs entry significantly drives down prices; still, prices of branded drugs facing generic competition continued to increase after generic market entry.

Objectives: Kids in Control OF Food (KICk-OFF) is a 5-day structured education program for 11- to 16-year-olds with type 1 diabetes mellitus (T1DM) who are using multiple daily insulin injections. This study evaluates the cost-effectiveness of the KICk-OFF education program compared with the usual care using data from the KICk-OFF trial.

Methods: The short-term within-trial analysis covers the 2-year postintervention period. Data on glycated hemoglobin (HbA1c), severe hypoglycemia, and diabetic ketoacidosis (DKA) were collected over a 2-year follow-up period. Sub-group analyses have been defined on the basis of baseline HbA1c being below 7.5 percent (58.5 mmol/mol) (low group), between 7.5 percent and 9.5 percent (80.3 mmol/mol) (medium group), and over 9.5 percent (high group). The long-term cost-effectiveness evaluation has been conducted by using The Sheffield Type 1 Diabetes Policy Model, which is a patient-level simulation model on T1DM. It includes long-term microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular (myocardial infarction, stroke, revascularization, and angina) diabetes-related complications and acute adverse events (severe hypoglycemia and DKA).

Results: The most favorable within-trial scenario for the KICk-OFF arm led to an incremental cost-effectiveness ratio (ICER) of £23,688 (base year 2009) with a cost-effectiveness probability of 41.3 percent. Simulating the long-term complications using the full cohort data, the mean ICER for the base case was £28,813 (base year 2011) and the probability of the KICk-OFF intervention being cost-effective at £20,000/QALY threshold was 42.6 percent, with considerable variation due to treatment effect duration. For the high HbA1c sub-group, the KICk-OFF arm was “dominant” (meaning it provided better health gains at lower costs than usual care) over the usual care arm in each scenario considered.

Conclusions: For the whole study population, the cost-effectiveness of KICk-OFF depends on the assumption for treatment effect duration. For the high baseline HbA1c sub-group, KICk-OFF arm was estimated to be dominant over the usual care arm regardless of the assumption on the treatment effect duration.

Objectives: Long-term follow-up of the Caries Management System (CMS) protocol demonstrated that regular monitoring and noninvasive management of dental caries is effective in reducing the number of caries-related events over a 7-year period. This analysis complements the authors’ original economic evaluation of the CMS by re-evaluating the per-protocol cost-effectiveness of the CMS approach.

Methods: An individual patient-simulation Markov model was developed previously, based on 3-year randomized-controlled trial (RCT) data, to simulate the incidence and progression of dental caries, and resultant interventions, and to evaluate the lifetime cost-effectiveness of the CMS versus standard dental care from the Australian private dental practitioner perspective (in which the baseline age distribution was similar to that of the Australian population). The 4-year posttrial follow-up data are used to re-evaluate the long-term cost-effectiveness of the CMS in a more real-life setting.

Results: The reduction in caries risk was maintained among those practices within which the CMS protocols were adhered to. The per-protocol model appears to be reasonably accurate at predicting the risk of restorative events in the posttrial follow-up period. The per-protocol lifetime cost per restorative event avoided is AUD1,980 (USD1,409; 1 AUD = 0.71 USD).

Conclusions: The current analysis confirms that the CMS approach is both effective, when the protocols are adhered to appropriately, and cost-effective compared with standard care in the Australian private practice setting.

Healthcare technology assessment (HTA) aims to support decisions as to which technologies should be used in which situations to optimize value. Because such decisions will create winners and losers, they are bound to be controversial. HTA, then, faces a dilemma: should it stay away from such controversies, remaining a source of incomplete advice and risking an important kind of marginalization, or should it enter the controversy? The question is a challenging one, because we lack agreement on principles that are fine grained enough to tell us what choices we should make. In this study, we will argue that HTA should take a stand on ethical issues raised by the technology that is being investigated. To do so, we propose adding a form of procedural justice to HTA to arrive at decisions that the public can regard as legitimate and fair. A fair process involves deliberation about the reasons, evidence, and rationales that are considered relevant to meeting population-health needs fairly. One important way to make sure that there is real deliberation about relevant reasons is to include a range of stakeholders in the deliberative process. To illustrate how such deliberation might work, we use the case of cochlear implants for deaf children.

Introduction: Hospital-based health technology assessment (HB-HTA) has been introduced to help hospital management in decision making about the adoption of new health technologies (HTs). We reviewed the accuracy of the expected medical impact of HTs assessed at our hospital, as well as the acceptance of this process by clinicians.

Methods: For each HT adopted between 2002 and 2011, a semi-structured interview with the involved clinician was conducted, assessing (i) the perceived utility of the HB-HTA process, (ii) the accuracy of the new HT's expected medical impact as compared with observed patient data from the year 2012, and (iii) the compliance with the indications of the HB-HTA report.

Results: Over the 10-year period, forty HB-HTAs were carried out, of which thirty-four led to acceptance. Twenty-seven of the twenty-eight clinicians involved in these thirty-four HTs accepted the interview and 85 percent acknowledged the utility of the HB-HTA process. Five of the thirty-four HTs were no longer in use. For the twenty-nine remaining HTs, observed patients’ number was as expected in eight, higher in four, lower in fifteen, and not available in two cases. Available average length of stay was 61 percent longer than expected. Two HTs had a higher complication rate and three a lower success rate. Indications evolved in 55 percent of HTs after a few years (seven restrictions, six broadenings, and three other changes).

Conclusions: A HB-HTA process is useful to improve quality in decision making. Follow-up analysis should routinely be performed to adapt HB-HTA reports’ conclusions to practical experience and new scientific evidence.

Objectives: Curative hepatectomy and tumor thrombectomy for hepatocellular carcinoma with complicating biliary tumor thrombosis (HCC/BTT) is associated with high surgical morbidity and mortality. This retrospective study evaluated the effectiveness and safety of neoadjuvant transcatheter arterial chemoembolization (TACE) in HCC/BTT patients scheduled for curative resection.

Methods: Thirty consecutive patients with diagnosed HCC/BTT were hospitalized for neoadjuvant TACE and elective curative liver resection (group A; n=20) or curative liver resection alone (group B; n=10). The primary outcome measure was median survival.

Results: Group A had a significantly shorter overall operative time (160±25 versus 190±35 min; p < .01) and duration of inflow control (14.3±3.6 versus 25.1±5.1 min; p < .01) and significantly less intraoperative blood loss (150±35 versus 520±75 ml; p < .01) and transfusion (100±40 versus 375±55 ml; p < .01) as compared to group B. Among patients undergoing both thrombectomy and curative resection, the median survival of group A was significantly longer than that of group B (28.5 [9–54] versus 21.5 [6–39] months; p < .01); among those who received thrombectomy alone, the median survival of group A was also significantly longer than that of group B (12.8 [6–25] versus 4.5 [2–7] months; p < .01).

Conclusions: Neoadjuvant TACE significantly reduced the surgical risk of curative liver resection and significantly prolonged median survival in HCC patients with complicating BTT.

Background: Oncotype DX (ODX), a tumor gene profiling test, has been incorporated into clinical guidelines to aid in adjuvant chemotherapy decision making for early-stage, hormone receptor positive breast cancer patients. Despite United States (U.S.) guidelines, less than half of eligible women receive testing. Reasons for low usage are unclear: Our objective was to better understand U.S. oncologists’ ODX uptake and how they use ODX during adjuvant chemotherapy decision making.

Methods: We conducted semi-structured, ~30-minute phone interviews with medical and surgical oncologists in one U.S. State using purposive sampling. Oncologists were included if they saw greater than or equal to five breast cancer patients per week. Recruitment ended upon thematic saturation. Interviews were recorded, transcribed, and double-coded using template analysis.

Results: During analysis, themes emerged across three domains. First, organizational factors (i.e., departmental structure, ODX marketing, and medical/insurance guidelines) influenced ease of ODX use. Second, oncologists referenced the influence of interpersonal factors (e.g., normative beliefs and peer use of ODX) over their own practices and recommendations. Third, intrapersonal factors (e.g., oncologist attitudes, perceived barriers, and research gaps) were discussed: although oncologists largely held positive attitudes about ODX, they reported challenges with interpreting intermediate scores for treatment decisions and explaining test results to patients. Finally, oncologists identified several research gaps.

Conclusions: As more tumor gene profiling tests are incorporated into cancer care for treatment decision making, it is important to understand their use in clinical practice. This study identified multi-level factors that influence ODX uptake into clinical practice, providing insights into facilitators and modifiable barriers that can be leveraged for improving ODX uptake to aid treatment decision making.

Background: To our knowledge, there has been no overall systematic review focusing on the methodological quality of full economic evaluation studies of self-management interventions. Our objective was to systematically review the literature of full economic evaluation studies of self-management interventions in adult chronic patients and to investigate their methodological quality and cost-effectiveness.

Methods: A data extraction form was developed to assess general and randomized controlled trial (RCT) -related characteristics, quality, of the RCTs, economic information and quality of the economic evaluation studies by means of a quality assessment (CHEC-list for trial-based studies, adjusted CHEC-list for model-based studies).

Results: Twenty-three reports were found. Sixteen studies (73 percent) lack information on the control intervention(s). Only one study fulfilled all three criteria for quality of RCTs and five studies (23 percent) did not meet any of these criteria. This review included one model-based study; the other studies were trial-based economic evaluation studies based on a RCT. Eight studies (35 percent) used a societal perspective and 12 (60 percent) synthesized costs and effects. Seven studies were categorized into the highest category (<15 score), nine studies into the “moderate” group (9–14 score), six studies received a “low” score (<8) on the CHEC-list. Eighteen studies found the self-management intervention(s) to be cost-effective compared with other interventions

Conclusions: Self-management interventions for adult chronic patients were heterogeneous and there was no clear, well-considered definition of self-management. Overall, the methodological quality of the full economic evaluation studies was moderate and, therefore, cost-effectiveness results must be interpreted with caution. Future research will benefit from further improvements in methodological quality of both economic study design and analysis, as well as a taxonomy for describing self-management interventions and their contents.

Objectives: To investigate the use, challenges and opportunities associated with using patient-reported outcomes (PROs) in studies with patients with rare lysosomal storage diseases (LSDs), we conducted interviews with researchers and health technology assessment (HTA) experts, and developed the methods for a systematic review of the literature. The purpose of the review is to identify the psychometrically sound generic and disease-specific PROs used in studies with patients with five LSDs of interest: Fabry, Gaucher (Type I), Niemann-Pick (Type B) and Pompe diseases, and mucopolysaccharidosis (Types I and II).

Methods: Researchers and HTA experts who responded to an email invitation participated in a telephone interview. We used qualitative content analysis to analyze the anonymized transcripts. We conducted a comprehensive literature search for studies that used PROs to investigate burden of disease or to assess the impact of interventions across the five LSDs of interest.

Results: Interviews with seven researchers and six HTA experts representing eight countries revealed five themes. These were: (i) the importance of using psychometrically sound PROs in studies with rare diseases, (ii) the paucity of disease-specific PROs, (iii) the importance of having PRO data for economic analyses, (iv) practical and psychometric limitations of existing PROs, and (v) suggestions for new PROs. The systematic review has been completed.

Conclusions: The interviews highlight current challenges and opportunities experienced by researchers and HTA experts involved in work with rare LSDs. The ongoing systematic review will highlight the experience, opportunities, and limitations of PROs in LSDs and provide suggestions for future research.