Plain English summary Background Continual improvements to health systems, products, and services are necessary for improvements in health. However, many of these improvements are not incorporated into everyday practice. When designing new health systems, products, and services, involving members of the healthcare community and the public with personal healthcare experience can help to make sure that improvements will be useful and relevant to others like them. Methods Together with healthcare workers and family members with healthcare experience, we developed and applied a step-by-step guide to involving those with personal experience in the design of health system improvements. Results Our guide has three phases— ‘Pre-Design’, ‘Co-Design’, and ‘Post-Design’. This paper describes each of these phases and illustrates how we applied them to our own project, which is to use virtual healthcare methods to improve care for children with chronic healthcare conditions and their families. In our own work, we found that healthcare workers and family members with personal healthcare experiences were able to use their knowledge and creativity to help us imagine how to improve care for children with chronic healthcare conditions and their families. We have created action items from these family member- and healthcare worker-identified needs, which we will use to shape our virtual healthcare system. Conclusions This paper may be useful for those seeking to involve members of the healthcare community and the public in the creation of better healthcare systems, products, and services. Abstract Background Challenges with the adoption, scale, and spread of health innovations represent significant gaps in the evidence-to-practice cycle. In the health innovation design process, a lack of attention paid to the needs of end-users, and subsequent tailoring of innovations to meet these needs, is a possible reason for this deficit. In the creative field of health innovation, which includes the design of healthcare products, systems (governance and organization mechanisms), and services (delivery mechanisms), a framework for both soliciting the needs of end-users and translating these needs into the design of health innovations is needed. Methods To address this gap, our team developed and applied a seven-step methodological framework, called A Generative Co-Design Framework for Healthcare Innovation. This framework was developed by an interdisciplinary team that included patient partners. Results This manuscript contributes a framework and applied exemplar for those seeking to engage end-users in the creative process of healthcare innovation. Through the stages of ‘Pre-Design’, ‘Co-Design’, and ‘Post-Design’, we were able to harness the creative insights of end-users, drawing on their experiences to shape a future state of care. Using an expository example of our own work, the DigiComp Kids project, we illustrate the application of each stage of the Framework. Conclusions A Generative Co-Design Framework for Healthcare Innovation provides healthcare innovators, applied health science researchers, clinicians, and quality improvement specialists with a guide to eliciting and incorporating the viewpoints of end-users while distilling practical considerations for healthcare innovation and design.

Purpose Mesenchymal epithelial transition factor ( MET) activation has been implicated as an oncogenic driver in epidermal growth factor receptor ( EGFR)–mutant non–small-cell lung cancer (NSCLC) and can mediate primary and secondary resistance to EGFR tyrosine kinase inhibitors (TKI). High copy number thresholds have been suggested to enrich for response to MET inhibitors. We examined the clinical relevance of MET copy number gain (CNG) in the setting of treatment-naive metastatic EGFR-mutant–positive NSCLC. Patients and Methods MET fluorescence in situ hybridization was performed in 200 consecutive patients identified as metastatic treatment-naïve EGFR-mutant–positive. We defined MET-high as CNG greater than or equal to 5, with an additional criterion of MET/centromeric portion of chromosome 7 ratiο greater than or equal to 2 for amplification. Time-to-treatment failure (TTF) to EGFR TKI in patients identified as MET-high and -low was estimated by Kaplan-Meier method and compared using log-rank test. Multiregion single-nucleotide polymorphism array analysis was performed on 13 early-stage resected EGFR-mutant–positive NSCLC across 59 sectors to investigate intratumoral heterogeneity of MET CNG. Results Fifty-two (26%) of 200 patients in the metastatic cohort were MET-high at diagnosis; 46 (23%) had polysomy and six (3%) had amplification. Median TTF was 12.2 months (95% CI, 5.7 to 22.6 months) versus 13.1 months (95% CI, 10.6 to 15.0 months) for MET-high and -low, respectively ( P = .566), with no significant difference in response rate regardless of copy number thresholds. Loss of MET was observed in three of six patients identified as MET-high who underwent postprogression biopsies, which is consistent with marked intratumoral heterogeneity in MET CNG observed in early-stage tumors. Suboptimal response (TTF, 1.0 to 6.4 months) to EGFR TKI was observed in patients with coexisting MET amplification (five [3.2%] of 154). Conclusion Although up to 26% of TKI-naïve EGFR-mutant–positive NSCLC harbor high MET CNG by fluorescence in situ hybridization, this did not significantly affect response to TKI, except in patients identified as MET-amplified. Our data underscore the limitations of adopting arbitrary copy number thresholds and the need for cross-assay validation to define therapeutically tractable MET pathway dysregulation in EGFR-mutant–positive NSCLC.

No abstract