Opportunities and challenges for the inclusion of patient preferences in the medical product life cycle: a systematic review

BACKGROUND: The inclusion of patient preferences (PP) in the medical product life cycle is a topic of growing interest to stakeholders such as academics, Health Technology Assessment (HTA) bodies, reimbursement agencies, industry, patients, physicians and regulators. This review aimed to understand the potential roles, reasons for using PP and the expectations, concerns and requirements associated with PP in industry processes, regulatory benefit-risk assessment (BRA) and marketing authorization (MA), and HTA and reimbursement decision-making. METHODS: A systematic review of peer-reviewed and grey literature published between January 2011 and March 2018 was performed. Consulted databases were EconLit, Embase, Guidelines International Network, PsycINFO and PubMed. A two-step strategy was used to select literature. Literature was analyzed using NVivo (QSR international). RESULTS: From 1015 initially identified documents, 72 were included. Most were written from an academic perspective (61%) and focused on PP in BRA/MA and/or HTA/reimbursement (73%). Using PP to improve understanding of patients' valuations of treatment outcomes, patients' benefit-risk trade-offs and preference heterogeneity were roles identified in all three decision-making contexts. Reasons for using PP relate to the unique insights and position of patients and the positive effect of including PP on the quality of the decision-making process. Concerns shared across decision-making contexts included methodological questions concerning the validity, reliability and cognitive burden of preference methods. In order to use PP, general, operational and quality requirements were identified, including recognition of the importance of PP and ensuring patient understanding in PP studies. CONCLUSIONS: Despite the array of opportunities and added value of using PP throughout the different steps of the MPLC identified in this review, their inclusion in decision-making is hampered by methodological challenges and lack of specific guidance on how to tackle these challenges when undertaking PP studies. To support the development of such guidance, more best practice PP studies and PP studies investigating the methodological issues identified in this review are critically needed

PERIODONTAL STATUS AND SELECTED CULTIVABLE ANAEROBIC MICROFLORA OF INSULIN-DEPENDENT JUVENILE DIABETICS

The periodontal status and subgingival microflora of insulin-dependent juvenile diabetic (JD) patients (n = 16, mean age = 11.3) were compared with that of their non-diabetic cohabiting healthy siblings (HS, n = 16, mean age = 13.2). JD patients were monitored every 3 months for levels of glycosylated hemoglobin (HbA1c) and clinical and microbial parameters were measured 6 weeks before drawing blood for levels of HbA1c (M% = 8.76). Clinical indices, measured for the entire permanent dentition, included: probing depth (PD), attachment level (AL), sulcus bleeding index (SBI), and plaque index (PI). Subgingival plaque samples were obtained at 2 sites from each subject; whenever possible, the site with the deepest probing depth and the mesial aspect of the maxillary right first molar were used. Microbial analyses were determined by cultural characteristics and biochemical tests. No significant differences were detected in any of the clinical indices for the entire dentition. The mean AL for JD sites was 2.32 +/- 0.83 mm and for HS sites was 2.2 +/- 0.85 mm. Mean percentage of total cultivable anaerobic microflora included Capnocytophaga spp. (JD, 13.21%; HS, 11%) and Porphyromonas gingivalis (JD, 5.1%; HS, 7.9%). Differences between the two groups were not statistically significant. When cluster analysis was performed on sampled sites, one cluster group in JD patients showed significantly elevated P. gingivalis and lower Capnocytophaga spp. levels as compared to the overall mean. The clinical parameters of this cluster were characterized by statistically significant greater loss of attachment and probing depth. These data would suggest few differences between JD patients and their HS in this population

Series: Pragmatic trials and real world evidence : Paper 3. Patient selection challenges and consequences

This paper addresses challenges of identifying, enrolling and retaining participants in a in a trial conducted within a routine care setting. All patients that are potential candidates for the treatments in routine clinical practice should be considered eligible for a pragmatic trial. To ensure generalizability, the recruited sample should have a similar distribution of the treatment effect modifiers as the target population. In practice this can be best achieved by including - within the selected sites - all patients without further selection. If relevant heterogeneity between subgroups is expected, increasing the relative proportion of the subgroup of patients in the heterogeneous trial could be considered (oversampling), or a separate trial in this subgroup can be planned. Selection will nevertheless occur. Low enrolment and loss to follow-up can introduce selection and can jeopardize validity as well as generalizability. Pragmatic trials are conducted in clinical practice rather than in a dedicated research setting, which could reduce recruitment rates. However, if a trial poses a minimal burden to the physician and the patient, and routine clinical practice is maximally adhered to, the participation rate may be high and loss to follow-up will not be a specific problem for pragmatic trials

Data set related to the article "Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF-1/CXCR4 signaling pathway"

This record contains raw data related to the article ""Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF-1/CXCR4 signaling pathway". Abstract Aims: Homozygosity for a four-missense single-nucleotide polymorphism haplotype of the human BPIFB4 gene is enriched in long-living individuals. Delivery of this longevity-associated variant (LAV) improved revascularisation and reduced endothelial dysfunction and atherosclerosis in mice through a mechanism involving the stromal cell-derived factor-1 (SDF-1). Here, we investigated if delivery of the LAV-BPIFB4 gene may attenuate the progression of diabetic cardiomyopathy. Methods and results: Compared with age-matched lean controls, diabetic db/db mice showed altered echocardiographic indices of diastolic and systolic function and histological evidence of microvascular rarefaction, lipid accumulation, and fibrosis in the myocardium. All these alterations, as well as endothelial dysfunction, were prevented by systemic LAV-BPIFB4 gene therapy using an adeno-associated viral vector serotype 9 (AAV9). In contrast, AAV9 wild-type-BPIFB4 exerted no benefit. Interestingly, LAV-BPIFB4-treated mice showed increased SDF-1 levels in peripheral blood and myocardium and up-regulation of the cardiac myosin heavy chain isoform alpha, a contractile protein that was reduced in diabetic hearts. SDF-1 up-regulation was instrumental to LAV-BPIFB4-induced benefit as both haemodynamic and structural improvements were inhibited by an orally active antagonist of the SDF-1 CXCR4 receptor. Conclusions: In mice with type-2 diabetes, LAV-BPIFB4 gene therapy promotes an advantageous remodelling of the heart, allowing it to better withstand diabetes-induced stress. These results support the viability of transferring healthy characteristics of longevity to attenuate diabetic cardiac disease

Data set related to the article "Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF-1/CXCR4 signaling pathway"

This record contains raw data related to the article ""Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF-1/CXCR4 signaling pathway". Abstract Aims: Homozygosity for a four-missense single-nucleotide polymorphism haplotype of the human BPIFB4 gene is enriched in long-living individuals. Delivery of this longevity-associated variant (LAV) improved revascularisation and reduced endothelial dysfunction and atherosclerosis in mice through a mechanism involving the stromal cell-derived factor-1 (SDF-1). Here, we investigated if delivery of the LAV-BPIFB4 gene may attenuate the progression of diabetic cardiomyopathy. Methods and results: Compared with age-matched lean controls, diabetic db/db mice showed altered echocardiographic indices of diastolic and systolic function and histological evidence of microvascular rarefaction, lipid accumulation, and fibrosis in the myocardium. All these alterations, as well as endothelial dysfunction, were prevented by systemic LAV-BPIFB4 gene therapy using an adeno-associated viral vector serotype 9 (AAV9). In contrast, AAV9 wild-type-BPIFB4 exerted no benefit. Interestingly, LAV-BPIFB4-treated mice showed increased SDF-1 levels in peripheral blood and myocardium and up-regulation of the cardiac myosin heavy chain isoform alpha, a contractile protein that was reduced in diabetic hearts. SDF-1 up-regulation was instrumental to LAV-BPIFB4-induced benefit as both haemodynamic and structural improvements were inhibited by an orally active antagonist of the SDF-1 CXCR4 receptor. Conclusions: In mice with type-2 diabetes, LAV-BPIFB4 gene therapy promotes an advantageous remodelling of the heart, allowing it to better withstand diabetes-induced stress. These results support the viability of transferring healthy characteristics of longevity to attenuate diabetic cardiac disease