Update on the ESCEO recommendation for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults.

BACKGROUND: In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. AIMS: The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. METHODS: This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. RESULTS: The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. CONCLUSION: The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.

Global Health in Preconception, Pregnancy and Postpartum Alliance: development of an international consumer and community involvement framework.

BACKGROUND: The goal of the Global Health in Preconception, Pregnancy and Postpartum (HiPPP) Alliance, comprising consumers and leading international multidisciplinary academics and clinicians, is to generate research and translation priorities and build international collaboration around healthy lifestyle and obesity prevention among women across the reproductive years. In doing so, we actively seek to involve consumers in research, implementation and translation initiatives. There are limited frameworks specifically designed to involve women across the key obesity prevention windows before (preconception), during and after pregnancy (postpartum). The aim of this paper is to outline our strategy for the development of the HiPPP Consumer and Community (CCI) Framework, with consumers as central to co-designed, co-implemented and co-disseminated research and translation. METHOD: The development of the framework involved three phases: In Phase 1, 21 Global HiPPP Alliance members participated in a CCI workshop to propose and discuss values and approaches for framework development; Phase 2 comprised a search of peer-reviewed and grey literature for existing CCI frameworks and resources; and Phase 3 entailed collaboration with consumers (i.e., members of the public with lived experience of weight/lifestyle issues in preconception, pregnancy and postpartum) and international CCI experts to workshop and refine the HiPPP CCI Framework (guided by Phases 1 and 2). RESULTS: The HiPPP CCI Framework's values and approaches identified in Phases 1-2 and further refined in Phase 3 were summarized under the following five key principles: 1. Inclusive, 2. Flexible, 3. Transparent, 4. Equitable, and 5. Adaptable. The HiPPP Framework describes values and approaches for involving consumers in research initiatives from design to translation that focus on improving healthy lifestyles and preventing obesity specifically before, during and after pregnancy; importantly it takes into consideration common barriers to partnering in obesity research during perinatal life stages, such as limited availability associated with family caregiving responsibilities. CONCLUSION: The HiPPP CCI Framework aims to describe approaches for implementing meaningful CCI initiatives with women in preconception, pregnancy and postpartum periods. Evaluation of the framework is now needed to understand how effective it is in facilitating meaningful involvement for consumers, researchers and clinicians, and its impact on research to improve healthy lifestyle outcomes.

Health in Preconception, Pregnancy and Postpartum Global Alliance: International Network Pregnancy Priorities for the Prevention of Maternal Obesity and Related Pregnancy and Long-Term Complications.

In this article, we describe the process of establishing agreed international pregnancy research priorities to address the global issues of unhealthy lifestyles and rising maternal obesity. We focus specifically on the prevention of maternal obesity to improve related clinical pregnancy and long-term complications. A team of multidisciplinary, international experts in preconception and pregnancy health, including consumers, were invited to form the Health in Preconception, Pregnancy and Postpartum (HiPPP) Global Alliance. As an initial activity, a priority setting process was completed to generate pregnancy research priorities in this field. Research, practice and policy gaps were identified and enhanced through expert and consumer consultation, followed by a modified Delphi process and Nominal Group Technique, including an international workshop. Research priorities identified included optimising: (1) healthy diet and nutrition; (2) gestational weight management; (3) screening for and managing pregnancy complications and pre-existing conditions; (4) physical activity; (5) mental health; and (6) postpartum (including intrapartum) care. Given extensive past research in many of these areas, research priorities here recognised the need to advance pregnancy research towards pragmatic implementation research. This work has set the agenda for large-scale, collaborative, multidisciplinary, implementation research to address the major public health and clinical issue of maternal obesity prevention.

Health in Preconception, Pregnancy and Postpartum Global Alliance: International Network Preconception Research Priorities for the Prevention of Maternal Obesity and Related Pregnancy and Long-Term Complications.

The preconception period is a key public health and clinical opportunity for obesity prevention. This paper describes the development of international preconception priorities to guide research and translation activities for maternal obesity prevention and improve clinical pregnancy outcomes. Stakeholders of international standing in preconception and pregnancy health formed the multidisciplinary Health in Preconception, Pregnancy, and Postpartum (HiPPP) Global Alliance. The Alliance undertook a priority setting process including three rounds of priority ranking and facilitated group discussion using Modified Delphi and Nominal Group Techniques to determine key research areas. Initial priority areas were based on a systematic review of international and national clinical practice guidelines, World Health Organization recommendations on preconception and pregnancy care, and consumer and expert input from HiPPP members. Five preconception research priorities and four overarching principles were identified. The priorities were: healthy diet and nutrition; weight management; physical activity; planned pregnancy; and physical, mental and psychosocial health. The principles were: operating in the context of broader preconception/antenatal priorities; social determinants; family health; and cultural considerations. These priorities provide a road map to progress research and translation activities in preconception health with future efforts required to advance evidence-translation and implementation to impact clinical outcomes.

Position statement from the European Board and College of Obstetrics & Gynaecology (EBCOG): The use of medicines during pregnancy - call for action.

Less than 10% of medicines approved by the FDA since 1980 have provided enough information as regards risks for birth defects associated with their use (Adam et al. (2011) [1]). Nevertheless, it is estimated that over 90% of pregnant women take over-the-counter (OTC) or prescription medication (Ke et al., 2014 [2]). Considering the fact that the use of medication in the period before conception and during lactation can also influence the development of the child, information on the impact of their usage during reproductive life is important for everyone. The lack of clear information on this topic results in situations where life-saving medication is discontinued, withheld or used in a reduced dosage by pregnant women, while on the other hand medicines with (potential) toxic effects are taken. This is unacceptable and it is a major public concern that must be addressed. Currently, Europe lacks a robust and comprehensive information system about medication use in reproductive life (from preconception, during pregnancy and during lactation). In order to improve maternal health, and subsequently the health of our next generation, reliable and up to date information should be made available. It should be readily accessible for both health care providers and women who are considering getting pregnant or who are already pregnant. In order to tackle this gap in public health, this paper describes current knowledge of the use of medicines before and during pregnancy. It calls upon all stakeholders involved in medical care, research and medicine regulation, such as policy makers, regulators and governmental agencies, to take action to protect patients and improve public health.

Position Statement from the European Board and College of Obstetrics & Gynaecology (EBCOG) : The use of medicines during pregnancy: call for action.

Less than 10% of medicines approved by the FDA since 1980 have provided enough information as regard risks for birth defects associated with their use [1]. Nevertheless, it is estimated that over 90% of pregnant women take over-the-counter (OTC) or prescription medication [2]. Considering the fact that the use of medication in the period before conception and during lactation can also influence the development of the child, information on the impact of their usage during reproductive life is important for everyone. The lack of clear information on this topic results in situations where life-saving medication is discontinued, withheld or used in a reduced dosage by pregnant women, while on the other hand medicines with (potential) toxic effects are taken. This is unacceptable and it is a major public concern that must be addressed. Currently, Europe lacks a robust and comprehensive information system about medication use in reproductive life (preconception, pregnancy and lactation). In order to improve maternal health, and subsequently the health of our next generation, reliable and up to date information should be made available. It should be readily accessible for both health care providers and women who are considering getting pregnant or who are already pregnant. In order to tackle this gap in public health, this paper describes current knowledge of the use of medicines before and during pregnancy. It calls upon all stakeholders involved in medical care, research and medicine regulation, such as policy makers, regulators and governmental agencies, to take action to protect patients and improve public health.