Development of live biotherapeutic products: a position statement of Asia-Pacific Microbiota Consortium

Objective
Live biotherapeutic products (LBPs) are biological products composed of living micro-organisms, developed to prevent, treat, or cure diseases. Examples include cultured strains of Akkermansia muciniphila and Christensenella minuta, as well as treatments using purified Firmicutes spores for recurrent Clostridioides difficile infections. There is a need for guidelines over the increasing interest in developing LBPs. A panel of microbiome experts from Asia-Pacific countries articulates their perspectives on key considerations for LBP development.

Design
Experts in microbiome research, microbiology, gastroenterology, internal medicine and biotherapeutics industry were invited to form a panel. During the 2023 Inauguration Conference of the Asia-Pacific Microbiota Consortium, an organised, iterative roundtable discussion was conducted to build expert consensus on critical issues surrounding the development of LBP.

Results
The consensus statements were organised into three main aspects: (a) rationales of LBP development, (b) preclinical studies and (c) preparation for clinical studies. The panel strongly recommended to prioritise human-derived and food-sourced strains for development, with indications based on clinical need and efficacy shown in studies. Preclinical evaluation should involve thorough screening, genotyping and phenotyping, as well as comprehensive in vitro and animal studies to assess functional mechanisms and microbiological safety. Rigorous cell banking practices and genetic monitoring are essential to ensure product consistency and safety throughout the manufacturing process. Clinical trials, including postmarketing surveillance, must be carefully designed and closely monitored, with robust safety and risk management protocols in place.

Conclusions
The development of LBP should be approached with a strong emphasis on microbiological evaluation, clinical relevance, scientific mechanisms and safety at every stage. These measures are essential to ensure the safety, effectiveness and long-term success of the product.

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One Meeting, Three Perspectives

In this narrative medicine essay, a mother, a palliative care physician, and a hospital chaplain describe a meeting discussing a young patient’s medical options for treating his rare brain tumor.

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Interventions to enable and reach patients with heart failure and their caregivers, with palliative care (TIER-HF-PC): a study protocol of a two-armed parallel group, open label randomised controlled trial that evaluates the effectiveness of a tiered model of palliative care in tertiary cardiac institutes in Singapore

Introduction
Palliative care (PC) improves quality of life (QOL). However, PC is currently delivered ‘too little, too late’ in heart failure (HF). Timely interventions to enable and reach patients with HF and their caregivers, with PC (TIER-HF-PC) is a novel, nurse coach-led model of PC that integrates PC into HF care. We will compare the effectiveness of TIER-HF-PC against usual care for improving patient and caregiver health outcomes. We will also evaluate implementation outcomes (such as care experience) of TIER-HF-PC.

Methods and analysis
In TIER-HF-PC, patients undergo regular distress screening. The intensity of PC treatments will be tiered based on the severity of problems detected. Minimally, all patients will receive PC education resources. Patients with moderate-intensity needs will receive PC health coaching. Patients with high-intensity needs will receive a PC physician consultation, on top of PC health coaching. Patients in usual care are not screened but can be referred to a PC physician based on cardiologist discretion.
We will recruit 240 English- or Mandarin-speaking patients with HF and up to 240 caregivers from 3 sites across 2 cardiac centres. Patients will be randomised in a 1:1 ratio to TIER-HF-PC or usual care. We will use an intention-to-treat approach for data analysis. Our primary outcome is patient QOL on the Kansas City Cardiomyopathy Questionnaire at 24 weeks. Secondary outcomes include patient healthcare utilisation, caregiver QOL and cost-effectiveness. All participants who received PC treatments will receive a service evaluation survey. Additionally, a sample of these participants and their treating healthcare staff will be purposively recruited for in-depth semistructured interviews on their TIER-HF-PC experience. Interviews will be thematically analysed. We will evaluate protocol fidelity through case notes and study process audits.

Ethics and dissemination
This study was approved by the SingHealth Institutional Ethics Review Board—review number: 2024–2213. Results of the study will be disseminated when data analysis is complete.

Trial registration number
NCT06244953.

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