FIGURE 1 - available via license: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Content may be subject to copyright.
Approximate Timelines, Characteristics, and Success Rates of the Standard Clinical Phases of Human Trials for Common Drugs
Source publication
Two major legislative actions since 2015, the 21st Century Cures Act of 2016 and the U.S. Food and Drug Administration (FDA) Reauthorization Act of 2017, contain significant provisions that potentially streamline drug development times, and by extension, may reduce costs. Evidence suggests, however, that development times have already been signific...
Context in source publication
Context 1
... after 30 days from filing there is no objection from the FDA, clinical studies can commence in what is generally divided into 3 phases of testing, progressing from small studies in healthy volunteers to large studies in targeted patient populations. Timelines, characteristics, and success rates of the standard clinical phases are summarized in Figure 1. ...
Citations
... Phase 0, often known as micro-dosing, is performed in human volunteers to learn about dosage tolerance (pharmacokinetics) before the drug is given to healthy people in a phase 1 study [2]. Timelines, characteristics, and success rates of the standard clinical phases are summarized in Figure 1 [3]. ...
... The relevance of biostatistics in clinical trials cannot be overstated in the advancement of novel pharmaceuticals and therapeutics. To ensure that new treatments are both safe and effective prior to [3] collaborate need a solid understanding of these ideas. By mandating CDISC standards (such as SDTM and ADaM (Analysis Dataset Model), define.xml, ...
Biostatistical analysis has emerged as one of the most crucial applications for clinical trial systems. The relevance of statistical analysis in clinical trials cannot be overstated in the advancement of novel pharmaceuticals and therapeutics. Data volumes, including effectiveness and safety summaries, are produced throughout the process of developing and approving novel medicines. Data standards developed by the Clinical Data Interchange Standards Consortium (CDISC) are well-established, widely accepted, and widely utilized by the pharmaceutical sector for submissions to regulatory bodies. Biostatistical programs like PRM, ODM, CDASH, SDTM, ADaM, SAS, and ARDM have come a long way in recent years, and this article highlights those developments. The present study has made an effort to report on the typical difficulties encountered when using biostatistical methods, as with every new discovery, there is always a potential pitfall. Even the main endpoint of the experiment might be improperly analysed without adequate validation of model assumptions. Biostatisticians must collaborate closely with physicians to choose the most suitable statistical methods for data assessment; otherwise, the results may be ambiguous or misleading. To guarantee that a clinical trial satisfies the requirements of regulatory agencies in drug approvals, future research should concentrate on strategies that can enhance the compliance and validation processes.
Introduction:
The new European Union (EU) Regulations for medical devices (MDs) and health technology assessment (HTA) are welcome developments that will hopefully increase the quality of clinical evidence for MDs and reduce fragmentation in the EU market access process. To fully exploit anticipated benefits, their respective assessment processes should be closely coordinated, particularly for promising, highly innovative MDs. Accelerated approval is worth exploring for certain categories of high-risk MDs to keep the EU regulatory process competitive compared to ad-hoc accelerated MD approval processes elsewhere (e.g., US).
Areas covered:
Problems observed in worldwide accelerated drug and MD regulatory approval programs are reviewed, including greater uncertainty in pre-market clinical evidence generation and lack of oversight for post-approval evidence requirements. Implications for MD approval, HTA and coverage are explored.
Expert opinion:
Through analysis of two decades of drug and MD accelerated approval programs worldwide, recommendations for an Accelerated Access Pathway for select innovative, high-risk MDs are proposed that can fit the EU context, leverage the two new regulations, increase opportunities for Expert Panels to provide timely advice regarding manufacturers' evidence generation plans along the MD lifecycle (pre-, post-market), and safely speed patient access while promoting increased collaboration among Member States on coverage decisions.
COVID-19 outburst initiated from the city of Wuhan in China in December 2019 and has been declared as a public health emergency of international concern. This pandemic portrays a spectrum of clinical complications, primarily affecting the respiratory system reported to be caused by a pathogen SARS-CoV-2 belonging to the family of beta coronavirus. Currently, the main objective of the government authorities of all affected countries and research organizations is to find a potential solution in the form of a pharmacological intervention or a vaccination to eradicate the disease and to have a long-term solution to deal with the pandemic. A multitude of anti-viral regimens is proposed based on the repurposing of currently available drugs for other issues or the compassionate use of drugs to immediately control and optimize the healthcare facilities. Meanwhile, a number of agencies are proposing new drug candidates to recreate the possibility of treating the disease. Similarly, a lot of research work is going on worldwide for the development of vaccination. Currently, a good number of candidates has finally reached the borders of Clinical Trials and are expected to be launched as soon as possible. However, the regulatory framework and authorization of these candidates is the most significant aspect of the whole scenario, which needs a specific set of time for validation purposes. The present work is widely focused on the general aspects of COVID-19 and the regulatory landscape for the emergency authorization of repurposed drug candidates, compassionate use of drugs, investigational entities, and vaccine development worldwide.
Supplementary information:
The online version contains supplementary material available at 10.1007/s13337-021-00684-5.
Currently, the search to identify treatments and vaccines for novel coronavirus disease (COVID-19) are ongoing. Desperation within the community, especially among the middle-and low-income groups acutely affected by the economic impact of forced lockdowns, has driven increased interest in exploring alternative choices of medicinal plant-based therapeutics. This is evident with the rise in unsubstantiated efficacy claims of these interventions circulating on social media. Based on enquiries received, our team of researchers was given the chance to produce evidence summaries evaluating the potential of complementary interventions in COVID-19 management. Here, we present and discuss the findings of four selected medicinal plants (Nigella sativa, Vernonia amygdalina, Azadirachta indica, Eurycoma longifolia), with reported antiviral, anti-inflammatory, and immunomodulatory effects that might be interesting for further investigation. Our findings showed that only A. indica reported positive antiviral evidence specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on preliminary in silico data while all four medicinal plants demonstrated differential anti-inflammatory or immunomodulatory effects. The definitive roles of these medicinal plants in cytokine storms and post-infection complications remains to be further investigated. Quality control and standardisation of medicinal plant-based products also needs to be emphasized. However, given the unprecedented challenges faced, ethnopharmacological research should be given a fair amount of consideration for contribution in this pandemic.
The global impact imposed by the coronavirus disease 2019 (COVID-19) pandemic may be soon alleviated by the introduction and world- wide dissemination of safe and effective vac- cines. This expedited timetable for development and approval of COVID-19 vaccines is an unprecedented extraordinary, concerted achievement by the scientific community. With the pending global rollout of vaccines, each with different mechanisms of action, physicians of various specialties will need to identify vul- nerable patient groups for special considera- tions or advice. In this commentary, we analyse the important considerations for COVID-19 vaccines in patients with inflammatory eye diseases. Scrutiny of immunogenicity and adverse effects, particularly antibody-depen- dent enhancement, would better help in coun- selling these patients undergoing vaccination. More research on pharmacovigilance would allow for tailored guidelines and personalised management strategies.
Biodegradable, hydrophobic, and injectable liquid polymers are capable of achieving the minimally invasive, sustained, and local release of drugs. These hydrophobic injectable polymers also have potential in the area of regenerative medicine where the biomaterial should be stable for a certain period and then degrade to allow the growth of cells/tissues. This review presents exclusive coverage of biocompatible hydrophobic injectable pasty or liquid polymers that can be injected without the use of any solvent for drug delivery, tissue augmentation, and regenerative medicine application. The synthesis methodologies of several major types of hydrophobic pasty polymers used in the biomedical fields and their properties with the foremost criteria to serve as injectable biomaterial for localized drug delivery and regenerative medicine is described. The hydrophobic biodegradable injectable polymers discussed are aliphatic polyesters, polycarbonates and polyanhydrides, prepared from: lactic acid, glycolic acid, caprolactone, aliphatic diols and diacids, hydroxy fatty acids, and triglycerides such as castor oil. Liquid hydrophobic polymers are efficient to release drugs locally and have the potential in regenerative medicine due to their simple and direct injection to the required site. This review summarizes the synthetic methodologies and desired properties of the biocompatible, hydrophobic and liquid polymers that can be injected directly for the application of localized drug delivery and regenerative medicine.
