bims-curels Biomed News
on Leigh syndrome
Issue of 2022‒12‒04
six papers selected by
Cure Mito Foundation

  1. Trials. 2022 Nov 28. 23(1): 966
      It is increasingly recognized that involving patients and the public in the design of clinical trials can lead to better recruitment, retention, and satisfaction. A recent scoping review determined that between 1985 and 2018, just 23 articles meeting quality criteria obtained feedback from clinical trial participants after a trial had been completed. In a timespan that presumably included thousands of trials across hundreds of indications, the paucity of the literature seems surprising, if not outright disappointing. By contrast, practitioners in the life sciences industry are increasingly incorporating patient research into their trial design process before, during, and after trial completion. Examples of approaches used include recruitment of "look alike" participant samples through online communities, surveys, and the use of smartphone apps to directly record participants' spoken reactions to trial materials like recruitment materials, site visit schedules, or informed consent materials. However, commercial organizations tend not to publish their findings, leading to a potential two-tier experience for trial participants depending on whether the trial they participate in will be industry-funded or government-funded. This seems problematic on a number of levels. Increasing regulatory, funder, and publisher interest in improving the inclusivity of clinical trial participants may act as a timely lever to spur patient-centered coproduction of trials. Until continuous feedback processes are the mandated, funded, and published norm, participating in a clinical trial will be more arduous than it needs to be.
    Keywords:  Patient and public involvement; Recruitment; Retention
  2. J Clin Pharmacol. 2022 Dec;62 Suppl 2 S38-S55
      Rare diseases represent a highly heterogeneous group of disorders with high phenotypic and genotypic diversity within individual conditions. Due to the small numbers of people affected, there are unique challenges in understanding rare diseases and drug development for these conditions, including patient identification and recruitment, trial design, and costs. Natural history data and real-world data (RWD) play significant roles in defining and characterizing disease progression, final patient populations, novel biomarkers, genetic relationships, and treatment effects. This review provides an introduction to rare diseases, natural history data, RWD, and real-world evidence, the respective sources and applications of these data in several rare diseases. Considerations for data quality and limitations when using natural history and RWD are also elaborated. Opportunities are highlighted for cross-sector collaboration, standardized and high-quality data collection using new technologies, and more comprehensive evidence generation using quantitative approaches such as disease progression modeling, artificial intelligence, and machine learning. Advanced statistical approaches to integrate natural history data and RWD to further disease understanding and guide more efficient clinical study design and data analysis in drug development in rare diseases are also discussed.
    Keywords:  disease progression modeling; natural history; rare diseases; real-world data; real-world evidence
  3. Adv Exp Med Biol. 2023 ;1396 255-273
      Metabolic diseases have important effects on the health and healthcare costs of an individual. It adversely affects various body processes. Metabolic diseases are characterized as the accumulation of many conditions that collectively increase a person's risk of atherosclerotic coronary disease, insulin, and diabetes mellitus intolerance, as well as vascular and neurological complications, such as stroke. Rare metabolic disease has also been reported in literatures and clinical research. Understanding the history and causes of the disease, associated symptoms, disease severity, physical and vital evaluations, etc. is recommended to provide or improve some appropriate therapeutic measure. The experience with patients starts with a critical and general presentation to a healthcare provider that may indicate potential conditions such as dyslipidemia, hypertension, and metabolic diseases. The main factors in the treatment and management of metabolic disorders are lifestyle changes. Whenever behavioral changes are not effective or cannot be implemented, pharmacotherapies should be initiated including for most of the rare diseases. Moreover, pharmaceutical molecules are the very commonly used therapies. The prospect of therapy through gene transfer into somatic cells unlocks a new field of treatment and opportunity for people affected by these genetic conditions. Like other medical treatments, many gene therapies can relieve some, though not every indications of a specific disease, which can increase patients' quality of life. Hormone-based therapies are also implemented in the treatment of metabolic diseases. It has been suggested to use herbal extracts with different forms of nano-drug delivery techniques, such as nanobiocomposites, solid lipid nanoparticles, nanoemulsions, green-synthesized gold, zinc oxide, and silver nanoparticles.
    Keywords:  Diabetes mellitus; Dyslipidemia; Hypertension; Metabolic diseases; Obesity; Rare diseases
  4. J Clin Pharmacol. 2022 Dec;62 Suppl 2 S27-S37
      A rare disease is defined as a condition affecting fewer than 200 000 people in the United States by the Orphan Drug Act. For rare diseases, it is challenging to enroll a large number of patients and obtain all critical information to support drug approval through traditional clinical trial approaches. In addition, over half of the population affected by rare diseases are children, which presents additional drug development challenges. Thus, maximizing the use of all available data is in the interest of drug developers and regulators in rare diseases. This brings opportunities for model-informed drug development to use and integrate all available sources and knowledge to quantitatively assess the benefit/risk of a new product under development and to inform dosing. This review article provides an overview of 4 broad categories of use of model-informed drug development in drug development and regulatory decision making in rare diseases: optimizing dose regimen, supporting pediatric extrapolation, informing clinical trial design, and providing confirmatory evidence for effectiveness. The totality of evidence based on population pharmacokinetic simulation as well as exposure-response relationships for efficacy and safety, provides the regulatory ground for the approval of an unstudied dosing regimen in rare diseases without the need for additional clinical data. Given the practical and ethical challenges in drug development in rare diseases, model-informed approaches using all collective information (eg, disease, drug, placebo effect, exposure-response in nonclinical and clinical settings) are powerful and can be applied throughout the drug development stages to facilitate decision making.
    Keywords:  biomarker; dose optimization; dose selection; model-informed drug development; pediatric extrapolation; rare disease
  5. HNO. 2022 Nov 28.
      As the continuation and implementation of findings from basic (pre-)clinical research, clinical trials make a significant contribution to medical research. They form the central building block of translational medicine and thus make a decisive contribution to bringing medical knowledge into general care. This helps to make possible a healthcare system that is aligned to the needs of patients and functions efficiently in the long term. Based on the specific objective, clinical trials must comply with national, but increasingly also with European and international regulatory requirements. In academia in particular, expertise in a variety of fields is required in order to make investigator-driven clinical trials a success. This expertise can be provided by a clinical trial center based within the institution conducting the trial.
    Keywords:  Biomedical translational science; Clinical trials as topic; Health care evaluation mechanisms; Patient-centered outcomes research; Quality assurance, health care
  6. Am J Med Genet C Semin Med Genet. 2022 Nov 30.
      Development of genetic tests for rare genetic diseases has traditionally focused on individual diseases. Similarly, development of new therapies occurred one disease at a time. With >10,000 rare genetic diseases, this approach is not feasible. Diagnosis of genetic disorders has already transcended old paradigms as whole exome and genome sequencing have allowed expedient interrogation of all relevant genes in a single test. The growth of newborn screening has allowed identification of diseases in presymptomatic babies. Similarly, the ability to develop therapies is rapidly expanding due to technologies that leverage platform technology that address multiple diseases. However, movement from the basic science laboratory to clinical trials is still hampered by a regulatory system rooted in traditional trial design, requiring a fresh assessment of safe ways to obtain approval for new drugs. Ultimately, the number of nucleic acid-based therapies will challenge the ability of clinics focused on rare diseases to deliver them safely with appropriate evaluation and long-term follow-up. This manuscript summarizes discussions arising from a recent National Institutes of Health conference on nucleic acid therapy, with a focus on scaling technologies for diagnosis of rare disorders and provision of therapies across the age and disease spectrum.