Comparative efficacy of leniolisib (CDZ173) versus standard of care on rates of respiratory tract infection and serum immunoglobulin M (IgM) levels among individuals with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): an externally controlled study.

Leniolisib, an oral, targeted phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, was well-tolerated and efficacious versus placebo in treating individuals with activated PI3Kδ syndrome (APDS), an ultra-rare inborn error of immunity (IEI), in a 12-week randomised controlled trial. However, longer-term comparative data versus standard of care are lacking. This externally controlled study compared the long-term effects of leniolisib on annual rate of respiratory tract infections and change in serum immunoglobulin M (IgM) levels versus current standard of care, using data from the leniolisib single-arm open-label extension study 2201E1 (NCT02859727) and the European Society for Immunodeficiencies (ESID) registry.

Effect of spirulina on risk of hospitalization among patients with COVID-19: the TOGETHER randomized trial.

Background: Algae-derived nutraceuticals, such as spirulina, have been reported to have biological activities that may minimize clinical consequences to COVID-19 infections.

Objectives: This study aimed to determine whether spirulina is an effective treatment for high-risk patients with early COVID-19 in an outpatient setting.

Methods: The TOGETHER trial is a placebo-controlled, randomized, platform trial conducted in Brazil.

Matched vs Nonmatched Placebos in a Randomized Trial of COVID-19 Treatments.

Importance: Matched placebo interventions are complex and resource intensive. Recent evidence suggests matched placebos may not always be necessary. Previous studies have predominantly evaluated potential bias of nonmatched placebos (ie, differing on dose, frequency of administration, or formulation) in pain and mental health, but to date no systematic examination has been conducted in infectious disease.

Assessing the performance of group-based trajectory modeling method to discover different patterns of medication adherence.

It is well known that medication adherence is critical to patient outcomes and can decrease patient mortality. The Pharmacy Quality Alliance (PQA) has recognized and identified medication adherence as an important indicator of medication-use quality. Hence, there is a need to use the right methods to assess medication adherence.

Totality of evidence of the effectiveness of repurposed therapies for COVID-19: Can we use real-world studies alongside randomized controlled trials?

Rapid and robust strategies to evaluate the efficacy and effectiveness of novel and existing pharmacotherapeutic interventions (repurposed treatments) in future pandemics are required. Observational "real-world studies" (RWS) can report more quickly than randomized controlled trials (RCTs) and would have value were they to yield reliable results. Both RCTs and RWS were deployed during the coronavirus disease 2019 (COVID-19) pandemic.

Data Challenges for Externally Controlled Trials: Viewpoint.

The preferred evidence of a large randomized controlled trial is difficult to adopt in scenarios, such as rare conditions or clinical subgroups with high unmet needs, and evidence from external sources, including real-world data, is being increasingly considered by decision makers. Real-world data originate from many sources, and identifying suitable real-world data that can be used to contextualize a single-arm trial, as an external control arm, has several challenges. In this viewpoint article, we provide an overview of the technical challenges raised by regulatory and health reimbursement agencies when evaluating comparative efficacy, such as identification, outcome, and time selection challenges.

Data capture and sharing in the COVID-19 pandemic: a cause for concern.

Routine health care and research have been profoundly influenced by digital-health technologies. These technologies range from primary data collection in electronic health records (EHRs) and administrative claims to web-based artificial-intelligence-driven analyses. There has been increased use of such health technologies during the COVID-19 pandemic, driven in part by the availability of these data.

Economic Evaluation of Cost and Time Required for a Platform Trial vs Conventional Trials.

Importance: Platform trial design allows the introduction of new interventions after the trial is initiated and offers efficiencies to clinical research. However, limited guidance exists on the economic resources required to establish and maintain platform trials.

Objective: To compare cost (US dollars) and time requirements of conducting a platform trial vs a series of conventional (nonplatform) trials using a real-life example.

Data flow within global clinical trials: a scoping review.

Objective: To document clinical trial data flow in global clinical trials published in major journals between 2013 and 2021 from Global South to Global North.

Design: Scoping analysis METHODS: We performed a search in Cochrane Central Register of Controlled Trials (CENTRAL) to retrieve randomised clinical trials published between 2013 and 2021 from . Studies were included if they involved recruitment and author affiliation across different country income groupings using World Bank definitions.

The Need for a Practical Approach to Evaluate the Effectiveness of COVID-19 Vaccines for Low- and Middle-Income Countries.

The global demand for coronavirus disease 2019 (COVID-19) vaccines currently far outweighs the available global supply and manufacturing capacity. As a result, securing doses of vaccines for low- and middle-income countries has been challenging, particularly for African countries. Clinical trial investigation for COVID-19 vaccines has been rare in Africa, with the only randomized clinical trials (RCTs) for COVID-19 vaccines having been conducted in South Africa.

Global incidence and prevalence of idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive debilitating lung disease with considerable morbidity. Heterogeneity in epidemiologic studies means the full impact of the disease is unclear.

Methods: A targeted literature search for population-based, observational studies reporting incidence and/or prevalence of IPF from January 2009 to April 2020 was conducted.

Moving forward in clinical research with master protocols.

With billions of dollars in research and development (R&D) funding continuing to be invested, the novel coronavirus disease 2019 (COVID-19) has become into a singular focus for the scientific community. However, the collective response from the scientific communities have seen poor return on investment, particularly for therapeutic research for COVID-19, revealing the existing weaknesses and inefficiencies of the clinical trial enterprise. In this article, we argue for the importance of structural changes to existing research programs for clinical trials in light of the lessons learned from COVID-19.

The role and challenges of cluster randomised trials for global health.

Evaluating whether an intervention works when trialled in groups of individuals can pose complex challenges for clinical research. Cluster randomised controlled trials involve the random allocation of groups or clusters of individuals to receive an intervention, and they are commonly used in global health research. In this paper, we describe the potential reasons for the increasing popularity of cluster trials in low-income and middle-income countries.

Clinical Trial Data Sharing for COVID-19-Related Research.

This paper aims to provide a perspective on data sharing practices in the context of the COVID-19 pandemic. The scientific community has made several important inroads in the fight against COVID-19, and there are over 2500 clinical trials registered globally. Within the context of the rapidly changing pandemic, we are seeing a large number of trials conducted without results being made available.

The Landscape of Emerging Randomized Clinical Trial Evidence for COVID-19 Disease Stages: A Systematic Review of Global Trial Registries.

Purpose: A multitude of randomized controlled trials (RCTs) have emerged in response to the novel coronavirus disease (COVID-19) pandemic. Understanding the distribution of trials among various settings is important to guide future research priorities and efforts. The purpose of this review was to describe the emerging evidence base of COVID-19 RCTs by stages of disease progression, from pre-exposure to hospitalization.

Reporting and design of randomized controlled trials for COVID-19: A systematic review.

Background: The novel coronavirus 2019 (COVID-19) pandemic has mobilized global research at an unprecedented scale. While challenges associated with the COVID-19 trial landscape have been discussed previously, no comprehensive reviews have been conducted to assess the reporting, design, and data sharing practices of randomized controlled trials (RCTs).

Purpose: The purpose of this review was to gain insight into the current landscape of reporting, methodological design, and data sharing practices for COVID-19 RCTs.

Interventions to improve birth outcomes of pregnant women living in low- and middle-income countries: a systematic review and network meta-analysis.

Improving the health of pregnant women is important to prevent adverse birth outcomes, such as preterm birth and low birthweight. We evaluated the comparative effectiveness of interventions under the domains of micronutrient, balanced energy protein, deworming, maternal education, and water sanitation and hygiene (WASH) for their effects on these adverse birth outcomes. For this network meta-analysis, we searched for randomized clinical trials (RCTs) of interventions provided to pregnant women in low- and middle-income countries (LMICs).

Interventions to improve linear growth during complementary feeding period for children aged 6-24 months living in low- and middle-income countries: a systematic review and network meta-analysis.

Optimizing linear growth in children during complementary feeding period (CFP) (6-24 months) is critical for their development. Several interventions, such as micronutrient and food supplements, deworming, maternal education, and water, sanitation and hygiene (WASH), could potentially be provided to prevent stunting, but their comparative effectiveness are currently unclear. In this study, we evaluated comparative effectiveness of interventions under these domains on child linear growth outcomes of height-for-age z-score (HAZ) and stunting (HAZ <-2SD) For this study, we searched for low- and middle-income country (LMIC)-based randomized clinical trials (RCTs) of aforementioned interventions provided to children during CFP.

Utilizing Bayesian predictive power in clinical trial design.

The Bayesian paradigm provides an ideal platform to update uncertainties and carry them over into the future in the presence of data. Bayesian predictive power (BPP) reflects our belief in the eventual success of a clinical trial to meet its goals. In this paper we derive mathematical expressions for the most common types of outcomes, to make the BPP accessible to practitioners, facilitate fast computations in adaptive trial design simulations that use interim futility monitoring, and propose an organized BPP-based phase II-to-phase III design framework.

Interventions to improve linear growth during exclusive breastfeeding life-stage for children aged 0-6 months living in low- and middle-income countries: a systematic review with network and pairwise meta-analyses.

Exclusive breastfeeding (EBF) during the first six months of life is critical for child's linear growth. While there is strong evidence in favor of EBF, the evidence with regards to other interventions for linear growth is unclear. We evaluated intervention domains of micronutrients, food supplements, deworming, maternal education, water sanitation and hygiene (WASH), and kangaroo care, for their comparative effectiveness on linear growth.

Accelerating Clinical Evaluation of Repurposed Combination Therapies for COVID-19.

As the global COVID-19 pandemic continues, unabated and clinical trials demonstrate limited effective pharmaceutical interventions, there is a pressing need to accelerate treatment evaluations. Among options for accelerated development is the evaluation of drug combinations in the absence of prior monotherapy data. This approach is appealing for a number of reasons.

Prevalence and incidence of HIV among female sex workers and their clients: modelling the potential effects of intervention in Rwanda.

Background: Rwanda has identified several targeted HIV prevention strategies, such as promotion of condom use and provision of antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) for female sex workers (FSWs). Given this country's limited resources, understanding how the HIV epidemic will be affected by these strategies is crucial.

Methods: We developed a Markov model to estimate the effects of targeted strategies to FSWs on the HIV prevalence/incidence in Rwanda from 2017 to 2027.

The Efficacy and Safety of Piribedil Relative to Pramipexole for the Treatment of Early Parkinson Disease: A Systematic Literature Review and Network Meta-Analysis.

Objectives: Patients with early Parkinson disease (PD) frequently defer initiation of levodopa treatment to minimize long-term complications. Nonergoline dopamine agonists, such as pramipexole and piribedil, are frequent first-line therapies for early PD patients, yet limited head-to-head randomized controlled trial (RCT) evidence exists for dopamine agonists in this population. We therefore conducted a systematic literature review and network meta-analysis.

Synthetic and External Controls in Clinical Trials - A Primer for Researchers.

There has been a rapid expansion in the use of non-randomized evidence in the regulatory approval of treatments globally. An emerging set of methodologies have been utilized to provide greater insight into external control data used for these purposes, collectively known as synthetic control methods. Through this paper, we provide the reader with a set of key questions to help assess the quality of literature publications utilizing synthetic control methodologies.