RESUMO
Agri-food systems are besieged by malnutrition, yield gaps, and climate vulnerability, but integrated, research-based responses in public policy, agricultural, value chains, and finance are constrained by short-termism and zero sum thinking. As they respond to current and emerging agri-food system challenges, decision makers need new tools that steer toward multi-sector, evidence-based collaboration. To support national agri-food system policy processes, the Integrated Agri-food System Initiative (IASI) methodology was developed and validated through case studies in Mexico and Colombia. This holistic, multi-sector methodology builds on diverse existing data resources and leverages situation analysis, modeled predictions, and scenarios to synchronize public and private action at the national level toward sustainable, equitable, and inclusive agri-food systems. Culminating in collectively agreed strategies and multi-partner tactical plans, the IASI methodology enabled a multi-level systems approach by mobilizing design thinking to foster mindset shifts and stakeholder consensus on sustainable and scalable innovations that respond to real-time dynamics in complex agri-food systems. To build capacity for these types of integrated, context-specific approaches, greater investment is needed in supportive international institutions that function as trusted in-region 'innovation brokers.' This paper calls for a structured global network to advance adaptation and evolution of essential tools like the IASI methodology in support of the One CGIAR mandate and in service of positive agri-food systems transformation.
Assuntos
Agricultura , Mudança Climática , Alimentos , Investimentos em Saúde , Política PúblicaRESUMO
BACKGROUND: Intravenous injection is the standard administration route of bortezomib; however, subcutaneous administration is an important alternative. We compared the efficacy and safety of subcutaneous versus intravenous bortezomib at the approved 1·3 mg/m(2) dose and twice per week schedule in patients with relapsed multiple myeloma. METHODS: This randomised, phase 3 study was undertaken at 53 centres in ten countries in Europe, Asia, and South America. Patients aged 18 years and older with relapsed multiple myeloma after one to three previous lines of therapy were randomly assigned to receive up to eight 21-day cycles of bortezomib 1·3 mg/m(2), on days 1, 4, 8, and 11, by subcutaneous injection or intravenous infusion. Randomisation was by an interactive voice response system based on a computer-generated randomisation schedule, stratified by number of previous lines and disease stage. Patients and treating physicians were not masked to treatment allocation. The primary objective was to show non-inferiority of subcutaneous versus intravenous bortezomib in terms of overall response rate (ORR) after four cycles in all patients with a diagnosis of measurable, secretory multiple myeloma who received one or more dose of drug (response-evaluable population). Non-inferiority was defined as retaining 60% of the intravenous treatment effect. This study is registered with ClinicalTrials.gov, number NCT00722566, and is ongoing for long-term follow-up. FINDINGS: 222 patients were randomly assigned to receive subcutaneous (n=148) or intravenous (n=74) bortezomib. The response-evaluable population consisted of 145 patients in the subcutaneous group and 73 in the intravenous group. Patients received a median of eight cycles (range one to ten) in both groups. ORR after four cycles was 42% in both groups (61 patients in subcutaneous group and 31 in intravenous group; ORR difference -0·4%, 95% CI -14·3 to 13·5), showing non-inferiority (p=0·002). After a median follow-up of 11·8 months (IQR 7·9-16·8) in the subcutaneous group and 12·0 months (8·1-15·6) in the intravenous group, there were no significant differences in time to progression (median 10·4 months, 95% CI 8·5-11·7, vs 9·4 months, 7·6-10·6; p=0·387) and 1-year overall survival (72·6%, 95% CI 63·1-80·0, vs 76·7%, 64·1-85·4; p=0·504) with subcutaneous versus intravenous bortezomib. Grade 3 or worse adverse events were reported in 84 (57%) patients in the subcutaneous group versus 52 (70%) in the intravenous group; the most common were thrombocytopenia (19 [13%] vs 14 [19%]), neutropenia (26 [18%] vs 13 [18%]), and anaemia (18 [12%] vs six [8%]). Peripheral neuropathy of any grade (56 [38%] vs 39 [53%]; p=0·044), grade 2 or worse (35 [24%] vs 30 [41%]; p=0·012), and grade 3 or worse (nine [6%] vs 12 [16%]; p=0·026) was significantly less common with subcutaneous than with intravenous administration. Subcutaneous administration was locally well tolerated. INTERPRETATION: Subcutaneous bortezomib offers non-inferior efficacy to standard intravenous administration, with an improved safety profile. FUNDING: Johnson & Johnson Pharmaceutical Research and Development, and Millennium Pharmaceuticals.