Exclusion of older persons from randomized controlled trials in type 2 diabetes: A cross-sectional study.

Background: Prevalence of type 2 diabetes increases with age. Both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) promote the enrollment of older patients to randomized controlled trials (RCTs) in diabetes. The objective of this study was to assess the eligibility criteria limiting the inclusion of older adults to RCTs in type 2 diabetes.

Exclusion of older patients from randomized clinical trials in Parkinson's disease.

Prevalence of Parkinson's disease (PD) increases with age. The purpose of this study was to evaluate the eligibility criteria in randomized clinical trials (RCTs) in PD, especially those limiting the enrollment of older adults. We examined RCTs of pharmacological and non-pharmacological anti-parkinsonian interventions registered with ClinicalTrials.

Placebo-controlled randomized clinical trials of antidepressants for major depressive disorder: Analysis of ClinicalTrials.gov, 2008-2022.

The purpose of this study was to analyze the key aspects of the design of contemporary placebo-controlled randomized clinical trials (RCTs) of antidepressants enrolling patients with major depressive disorder (MDD) aged 18 years or older, especially the outcome measures and the eligibility criteria. The study included 122 RCTs registered with ClinicalTrials.gov and started from 2008 through 2022.

Exclusion of older adults from randomized controlled trials in rheumatoid arthritis.

Objectives: To assess eligibility criteria that either explicitly or implicitly exclude older patients from randomized controlled trials (RCTs) in RA.

Methods: Our analysis included RCTs of pharmacological interventions registered with ClinicalTrials.gov and started between 2013 and 2022.

Exclusion of older adults from clinical trials in cancer-related pain.

Pain is one of the most common symptoms in cancer patients including older adults. The objective of this study was to evaluate the enrollment criteria that can limit the inclusion of older adults in clinical trials concerning cancer-related pain (CRP). The study included 356 trials registered with ClinicalTrials.

ClinicalTrials.gov as a Source of Information About Expanded Access Programs: Cohort Study.

Background: ClinicalTrials.gov (CT.gov) is the most comprehensive internet-based register of different types of clinical studies.

Conflicts of interest in oncology expanded access studies.

Expanded access is a treatment use of investigational drugs, biologicals or medical devices outside of clinical trials. The purpose of our study was to assess self-reported conflicts of interest (COIs) in oncology expanded access studies. One hundred fifty-eight oncology expanded access studies published from 2013 through 2020 were included.

Public availability of results of ClinicalTrials.gov-registered expanded access studies.

Aims: Expanded access is the use of investigational treatments outside of clinical trials. Results of expanded access studies provide insights into how investigational treatments work in real-world settings. The objective of this study was to evaluate public availability of results of expanded access studies.

The Presence of Bacteriophages in the Human Body: Good, Bad or Neutral?

The presence of bacteriophages (phages) in the human body may impact bacterial microbiota and modulate immunity. The role of phages in human microbiome studies and diseases is poorly understood. However, the correlation between a greater abundance of phages in the gut in ulcerative colitis and diabetes has been suggested.

Phage Therapy: Towards a Successful Clinical Trial.

While phage therapy carried out as compassionate use (experimental therapy) has recently flourished, providing numerous case reports of supposedly healed patients, clinical trials aiming to formally prove their value in accord with current regulatory requirements have failed. In light of the current issue of increasing antibiotic resistance, the need for a final say regarding the place of phage therapy in modern medicine is evident. We analyze the possible factors that may favor success or lead to the failure of phage therapy: quality of phage preparations, their titer and dosage, as well as external factors that could also contribute to the outcome of phage therapy.

Ethics framework for treatment use of investigational drugs.

Background: Expanded access is the use of investigational drugs (IDs) outside of clinical trials. Generally it is performed in patients with serious and life-threatening diseases who cannot be treated satisfactorily with authorized drugs. Legal regulations of expanded access to IDs have been introduced among others in the USA, the European Union (EU), Canada and Australia.

Ethics codes and medical decision making.

Objective: The objective of this study is to analyze guidance about medical decision making contained in ethics codes. The primary question we address is which of the main decision-making models - informed decision making (IDM), shared decision making (SDM), or paternalism - is promoted by these codes.

Methods: We manually searched codes of medical ethics for guidance on medical decision making.

Anti-phage serum antibody responses and the outcome of phage therapy.

We examined the appearance of serum anti-phage antibodies in 25 patients with chronic sinusitis treated with phage therapy (PT). Approximately 30% of patients with weak antibody responses responded positively to PT, which was similar to the results of treatment achieved in a group of patients with high antibody production. In addition, there was no correlation between antibody level and the outcome of PT.

Sepsis, Phages, and COVID-19.

Phage therapy has emerged as a potential novel treatment of sepsis for which no decisive progress has been achieved thus far. Obviously, phages can help eradicate local bacterial infection and bacteremia that may occur in a syndrome. For example, phages may be helpful in correcting excessive inflammatory responses and aberrant immunity that occur in sepsis.

Legal regulations, ethical guidelines and recent policies to increase transparency of clinical trials.

Timely and accurate dissemination of outcomes is essential to accomplish main benefits of scientific research including clinical trials. Clinical trial results can be disseminated in two main ways: by publication in a peer-reviewed journal and by posting on a publicly available clinical trial register. The credibility of the literature on clinical trials is significantly diminished because a high percentage of trials is not published.

Inhibitory Effects of Bacteriophage Preparations on Adenoviral Replication.

Background/aims: Bacteriophages (phages) are viruses of bacteria. Escherichia coli phage (T4) can potentially interfere with adsorption of HAdV-5 to cellular integrins by its KGD motif, while staphylococcal A5/80 phage does not possess this structure. The objective of this study was to investigate the effects of T4 and A5/80 phage preparations on type 5 human adenovirus (HAdV-5) DNA synthesis and the expression of HAdV-5 genes.

Phage therapy: Current status and perspectives.

The spread of antimicrobial resistant bacterial pathogens combined with the lack of new drug classes in the antibiotic pipeline causes a resurgence of the use of bacterial viruses (phages) to treat bacterial infections (phage therapy [PT]). There has been a substantial increase in patients subjected to this experimental therapy and emergence of new PT centers in Europe and the United States paralleled by one clinical trial completed in accord with good medical practice (GMP) requirements and a few others underway. What is more, evidence has been accumulating to suggest that phages can also exert anti-inflammatory and immunomodulatory action which opens new pathways for the development of novel targets for PT.

Compassionate use of unauthorized drugs: Legal regulations and ethical challenges.

Compassionate use (also referred to as expanded access) is therapeutic use of unauthorized drugs outside of clinical trials. The objective of this review is to discuss practical aspects of the current legal regulations concerning compassionate use that have been introduced in the European Union, the USA (both the Food and Drug Administration regulations and Right-to-try laws), Canada and Australia. We also present main ethical challenges associated with use of unauthorized drugs such as possible difficulties with obtaining informed consent and fair patient selection.