Value-based evidence across health care sectors: a push for transparent real-world studies, data, and evidence dissemination.

There is currently a heightened need for transparency in pharmaceutical sectors. The inclusion of real-world (RW) evidence, in addition to clinical trial evidence, in decision-making processes, was an important step forward toward a more inclusive established value proposition. This advance has introduced new transparency challenges. Increasing transparency is a critical step toward accelerating improvement in type, quality, and access to data, regardless of whether these originate from clinical trials or from RW studies. However, so far, advances in transparency have been relatively restricted to clinical trials, and there remains a lack of similar expectations or standards of transparency concerning the generation and reporting of RW data. This perspective paper aims to highlight the need for transparency concerning RW studies, data, and evidence across health care sectors, to identify areas for improvement, and provide concrete recommendations and practices for the future. Specific issues are discussed from different stakeholder perspectives, culminating in recommended actions, from individual stakeholder perspectives, for improved RW study, data, and evidence transparency. Furthermore, a list of potential guidelines for consideration by stakeholders is proposed. While recommendations from different stakeholder perspectives are made, true transparency in the processes involved in the generation, reporting, and use of RW evidence will require a concerted effort from all stakeholders across health care sectors.

Peer Review and Transparency in Evidence-Source Selection in Value and Health Technology Assessment.

OBJECTIVES: Value and health technology assessment (V/HTA) is often used in clinical, access, and reimbursement decisions. V/HTA data-source selection may not be transparent, which is a necessary element for stakeholder understanding and trust and for fostering accountability among decision makers. Peer review is considered one mechanism for judging data trustworthiness. Our objective was (1) to use publicly available documentation of V/HTA methods to identify requirements for inclusion of peer-reviewed evidence sources, (2) to compare and contrast US and non-US approaches, and (3) to assess evidence sources used in published V/HTA reports. METHODS: Publicly available methods documentation from 11 V/HTA organizations in North America and Europe were manually searched and abstracted for descriptions of requirements and recommendations regarding search strategy and evidence-source selection. The bibliographies of a subset of V/HTA reports published in 2018 were manually abstracted for evidence-source types used in each. RESULTS: Heterogeneity in evidence-source retrieval and selection was observed across all V/HTA organizations, with more pronounced differences between US and non-US organizations. Not all documentation of organizations' methods address the evidence-source selection processes (7 of 11), and few explicitly reference peer-reviewed sources (3 of 11). Documentation of the evidence-source selection strategy was inconsistent across reports (6 of 13), and the level of detail provided varied across organizations. Some information on evidence-source selection was often included in confidential documentation and was not publicly available. CONCLUSIONS: Disparities exist among V/HTA organizations in requirements and guidance regarding evidence-source selection. Standardization of evidence-source selection strategies and documentation could help improve V/HTA transparency and has implications for decision making based on report findings.

Patient burden of Sjögren's: a comprehensive literature review revealing the range and heterogeneity of measures used in assessments of severity.

CONTEXT: The severity of Sjögren's syndrome has been evaluated using a wide variety of clinical measures and patient-reported outcomes (PROs). This may contribute to the lack of clarity concerning the burden of Sjögren's from the patient perspective. OBJECTIVE: To perform a comprehensive peer-reviewed literature analysis of the patient aspects of Sjögren's, focusing on PROs, to investigate the complexity underlying the evaluation of the syndrome and to elucidate the discordance between the different measures. METHODS: We searched Embase for articles published between January 2005 and September 2015. Research articles, clinical and diagnostic reviews, and validation studies with a focus on patient aspects of Sjögren's were selected as the primary information source. RESULTS: 157 articles met the eligibility criteria. A wide variety of assessment measures used to evaluate glandular, extraglandular and functional domains were observed. Many different, non-validated Visual Analogue Scales, with a wide range of anchor words, were used in the quantification of Sjögren's disease burden, impeding comparisons between studies. Relatively few clinical trials of drug therapies used validated scales: European League Against Rheumatism Sjögren's Syndrome Patient Reported Index was used most often for symptom assessment and 36 Item Short Form Survey for quality of life (QoL). CONCLUSION: A wide range and diversity of measures are used to evaluate the patient burden of Sjögren's; most are not validated for use in this disease. PRO endpoints, validated specifically in Sjögren's, that demonstrate improvement are needed. These measures should focus on QoL aspects important to patients and will most likely involve gauging change in function rather than patient-reported symptoms.

Systematic review of clinical, humanistic, and economic outcome comparisons between radiographic and non-radiographic axial spondyloarthritis.

OBJECTIVE: To evaluate similarities and differences between non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) with regard to treatment effects and clinical, humanistic, and economic burdens. METHODS: In this systematic literature review, ACR 2015, EULAR 2015, EMBASE, and PubMed were searched for studies published between January 2010 and September 2015 that compared predefined clinical, humanistic, and economic aspects in nr-axSpA and AS. Publications were processed according to PRISMA guidelines, analyzed according to four research questions, and assessed for the GRADE level of evidence. RESULTS: Of 220 titles screened, 50 studies were evaluable. Treatment effects were reported by 22; clinical, humanistic, and economic burdens were specified by 38, 4, and 0, respectively. Fewer patients with increased C-reactive protein levels, less extensive structural damage, slower radiographic progression, and significantly lower Bath AS Metrology and Bath AS Functional Indices were reported for nr-axSpA than for AS. In contrast, the Bath AS Disease Activity Index, AS Disease Activity Score, and health-related quality of life were similar, indicating comparable clinical and humanistic burdens. Response to conventional therapies and TNFα inhibitors was similar between nr-axSpA and AS patients, although TNFα inhibitors were prescribed less frequently to nr-axSpA patients. CONCLUSIONS: Whether nr-axSpA is regarded as an early form of AS or as a distinct disease entity, it represents an important subgroup of axSpA. Ongoing clinical trials may provide the required evidence for a specified indication for TNFα inhibitors, important to prevent off-label use. Further research is crucial to better understand the disease spectrum and predictors of progression.

Comparison of contractile responses to donitriptan and sumatriptan in the human middle meningeal and coronary arteries.

Donitriptan is a potent, high efficacy agonist at 5-HT(1B/1D) receptors. We investigated the contractile effects of donitriptan and sumatriptan on human isolated blood vessels of relevance to therapeutic efficacy in migraine (middle meningeal artery) and coronary adverse events (coronary artery). Furthermore, using the concentration-response curves in the middle meningeal artery, we predicted the plasma concentration needed for the therapeutic effect of donitriptan. Both donitriptan and sumatriptan contracted the middle meningeal artery with similar apparent efficacy (E(max): 103+/-8% and 110+/-12%, respectively), but the potency of donitriptan (pEC(50): 9.07+/-0.14) was significantly higher than that of sumatriptan (pEC(50): 7.41+/-0.08). In the coronary artery, the contraction to donitriptan was biphasic with a significantly higher maximal response (E(max): 29+/-6%) than sumatriptan (E(max): 14+/-2%; pEC(50): 5.71+/-0.16), yielding two distinct pEC(50) values (8.25+/-0.16 and 5.60+/-0.24). Incubation with the 5-HT(2) receptor antagonist ketanserin (10 microM) eliminated the low affinity component of the concentration-response curve of donitriptan and the resultant E(max) and pEC(50) were 9+/-2% and 7.33+/-0.21, respectively. Ketanserin was without effect on the sumatriptan-induced contraction. Based on the middle meningeal artery contraction, concentrations (C(max)) of donitriptan that may be expected to have a therapeutic efficacy equivalent to that of 50 and 100 mg sumatriptan are predicted to be around 2.5 and 4.3 nM, respectively. Such concentrations are likely to induce only a small coronary artery contraction of 2.9+/-1.5% and 3.8+/-2.0%, respectively; these are not different from those by C(max) concentrations of sumatriptan (1.7+/-0.4% or 2.2+/-0.4%). The present results suggest that, like sumatriptan, donitriptan exhibits cranioselectivity and would be effective in aborting migraine attacks with a similar coronary side-effect profile as sumatriptan.