BackgroundPatients and their families have become more active in healthcare systems and research. The value of patient involvement is particularly relevant in the area of rare diseases, where patients face delayed diagnoses and limited access to effective therapies due to the high level of uncertainty in market approval and reimbursement decisions. It has been suggested that patient involvement may help to reduce some of these uncertainties. This review explored existing and proposed roles for patients, families, and patient organizations at each stage of the lifecycle of therapies for rare diseases (i.e., orphan drug lifecycle).MethodsA scoping review was conducted using methods outlined by Arksey and O’Malley. To validate the findings from the literature and identify any additional opportunities that were missed, a consultative webinar was conducted with members of the Patient and Caregiver Liaison Group of a Canadian research network.ResultsExisting and proposed opportunities for involving patients, families, and patient organizations were reported throughout the orphan drug lifecycle and fell into 12 themes: research outside of clinical trials; clinical trials; patient reported outcomes measures; patient registries and biorepositories; education; advocacy and awareness; conferences and workshops; patient care and support; patient organization development; regulatory decision-making; and reimbursement decision-making. Existing opportunities were not described in sufficient detail to allow for the level of involvement to be assessed. Additionally, no information on the impact of involvement within specific opportunities was found. Based on feedback from patients and families, documentation of existing opportunities within Canada is poor.ConclusionsOpportunities for patient, family, and patient organization involvement exist throughout the orphan drug lifecycle. However, based on the information found, it is not possible to determine which opportunities would be most effective at each stage.Electronic supplementary materialThe online version of this article (10.1186/s13023-017-0738-6) contains supplementary material, which is available to authorized users.

The generation of a 7.5x dog genome assembly provides exciting new opportunities to interpret tumor-associated chromosome aberrations at the biological level. We present a genomic microarray for array comparative genomic hybridization (aCGH) analysis in the dog, comprising 275 bacterial artificial chromosome (BAC) clones spaced at intervals of approximately 10 Mb. Each clone has been positioned accurately within the genome assembly and assigned to a unique chromosome location by fluorescence in situ hybridization (FISH) analysis, both individually and as chromosome-specific BAC pools. The microarray also contains clones representing the dog orthologues of 31 genes implicated in human cancers. FISH analysis of the 10-Mb BAC clone set indicated excellent coverage of each dog chromosome by the genome assembly. The order of clones was consistent with the assembly, but the cytogenetic intervals between clones were variable. We demonstrate the application of the BAC array for aCGH analysis to identify both whole and partial chromosome imbalances using a canine histiocytic sarcoma case. Using BAC clones selected from the array as probes, multicolor FISH analysis was used to further characterize these imbalances, revealing numerous structural chromosome rearrangements. We outline the value of a combined aCGH/FISH approach, together with a well-annotated dog genome assembly, in canine and comparative cancer studies.

The domestic dog continues to represent an influential model organism for comparative biomedical research owing to the numerous genetic and pathophysiological similarities shared between human and dog diseases. The combined availability of a high-quality genome assembly and a 1 Mb-resolution genome-assembly integrated bacterial artificial chromosome (BAC) panel now provides the essential resources to combine cytogenetic and computational analyses to determine the precise locations of chromosome breakpoint regions within aberrant karyotypes. In this study we demonstrate the synergy of using a such a combined in-situ/in-silico approach to define chromosome breakpoints using the naturally occurring breakpoint present on all canine X chromosomes--the pseudoautosomal breakpoint (PAB). In so doing we have further characterized the canine pseudoautosomal region (PAR) to extend approximately 6.6 Mb from the telomeric end of CFA Xp and established that the canine PAB is contained within a 2 kb region. Our characterization of the canine PAR allowed for the comparative study of gene content across previously defined mammalian PARs and indicates that the canine PAB is contained with the gene Shroom2. The future application of the approach demonstrated in this study will prove useful when seeking to identify the genomic sequences surrounding recurrent chromosome breakpoints present in canine cancers.

We describe an evidence-based framework to define and assess the impact of quality improvement (QI) in public health. Developed to address programmatic and research-identified needs for articulating the value of public health QI in aggregate, this framework proposes a standardized set of measures to monitor and improve the efficiency and effectiveness of public health programs and operations. We reviewed the scientific literature and analyzed QI initiatives implemented through the Centers for Disease Control and Prevention’s National Public Health Improvement Initiative to inform the selection of 5 efficiency and 8 effectiveness measures. This framework provides a model for identifying the types of improvement outcomes targeted by public health QI efforts and a means to understand QI’s impact on the practice of public health.

Opportunities for patients and families to contribute their 'lived experience' are needed throughout the orphan drug lifecycle, but the ideal mechanisms for providing this input have yet to be determined.

No abstract

Introduction Drugs for rare diseases (DRDs) offer important health benefits, but challenge traditional health technology assessment, reimbursement, and pricing processes due to limited effectiveness evidence. Recently, modified processes to address these challenges while improving patient access have been proposed in Canada. This review examined processes in 12 jurisdictions to develop recommendations for consideration during formal government-led multi-sectoral discussions currently taking place in Canada. Methods (i) A scoping review of DRD reimbursement processes, (ii) key informant interviews, (iii) a case study of evaluations for and the reimbursement status of a set of 7 DRDs, and (iv) a virtual, multi-stakeholder consultation retreat were conducted. Results Only NHS England has a process specifically for DRDs, while Italy, Scotland, and Australia have modified processes for eligible DRDs. Almost all consider economic evaluations, budget impact analyses, and patient-reported outcomes; but less than half accept surrogate measures. Disease severity, lack of alternatives, therapeutic value, quality of evidence, and value for money are factors used in all decision-making process; only NICE England uses a cost-effectiveness threshold. Budget impact is considered in all jurisdictions except Sweden. In Italy, France, Germany, Spain, and the United Kingdom, specific factors are considered for DRDs. However, in all jurisdictions opportunities for clinician/patient input are the same as those for other drugs. Of the 7 DRDs included in the case study, the number that received a positive reimbursement recommendation was highest in Germany and France, followed by Spain and Italy. No relationship between recommendation type and specific elements of the pricing and reimbursement process was found. Conclusions Based on the collective findings from all components of the project, seven recommendations for possible action in Canada are proposed. These focus on defining “appropriate access”, determining when a “full” HTA may not be needed, improving coordination among stakeholder groups, developing a Canadian framework for Managed Access Plans, creating a pan-Canadian DRD/rare disease data infrastructure, genuine and continued engagement of patient groups and clinicians, and further research on different decision and financing options, including MAPs.

Introduction Continuous quality improvement is a central tenet of the Public Health Accreditation Board’s (PHAB) national voluntary public health accreditation program. Similarly, the Centers for Disease Control and Prevention launched the National Public Health Improvement Initiative (NPHII) in 2010 with the goal of advancing accreditation readiness, performance management, and quality improvement (QI). Objective Evaluate the extent to which NPHII awardees have achieved program goals. Design NPHII awardees responded to an annual assessment and program monitoring data requests. Analysis included simple descriptive statistics. Setting Seventy-four state, tribal, local, and territorial public health agencies receiving NPHII funds. Participants NPHII performance improvement managers or principal investigators. Main Outcome Measure(s) Development of accreditation prerequisites, completion of an organizational self-assessment against the PHAB Standards and Measures, Version 1.0, establishment of a performance management system, and implementation of QI initiatives to increase efficiency and effectiveness. Results Of the 73 responding NPHII awardees, 42.5% had a current health assessment, 26% had a current health improvement plan, and 48% had a current strategic plan in place at the end of the second program year. Approximately 26% of awardees had completed an organizational PHAB self-assessment, 72% had established at least 1 of the 4 components of a performance management system, and 90% had conducted QI activities focused on increasing efficiencies and/or effectiveness. Conclusions NPHII appears to be supporting awardees’ initial achievement of program outcomes. As NPHII enters its third year, there will be additional opportunities to advance the work of NPHII, compile and disseminate results, and inform a vision of high-quality public health necessary to improve the health of the population.