The drug development process encompasses a series of phased clinical trials, typically categorized as phases 0 (optional), 1, 2, 3, and 4. Phases 0, 1, and 2 primarily serve for premarket assessment, while phase 4 focuses on post-marketing evaluation. Phase 1 and 2 trials are often referred to as 'early phase trials,' while phase 3 trials are known as 'late phase trials,' 'pivotal studies,' or 'confirmatory trials.' Notably, the Code of Federal Regulations (Title 21 pertaining to the FDA) does not explicitly describe each phase of clinical trials. Instead, it mandates 'adequate and well-contro ..read more

Clinical development programs for drugs and biological products include phased clinical trials ranging from Phase 0, 1, 2, 3, and 4.  Phase 0 study is not typically needed. Phases 1, 2, and 3 studies are typical pre-market clinical trials and Phase 4 studies are post-market clinical trials. There are a lot of articles and books discussing the clinical trial phases. I borrowed some illustrations/slides from FDA's 'Clinical Research Phase Studies" and other web resources: Phase 0 Clinical Trials: Phase 0 trials, also known as exploratory or pre-phase I trials, involve a small number of par ..read more

Traditionally, drug approvals relied on at least two adequate and well-controlled studies, each convincing on its own, to establish effectiveness. The adequate and well-controlled (A&WC) studies are referring to the randomized, controlled trials (RCTs). However, in some special situations (such as orphan drug development), one adequate and well-controlled study may be sufficient and the evidences from sources other than RCTs may be considered as substantial evidence of effectiveness.  In FDAs guidance for industry (September, 2023) "Demonstrating Substantial Evidence of Effectiveness ..read more

In early 2024, the FDA unveiled its latest drug guidance for the industry titled "Use of Data Monitoring Committees in Clinical Trials." This forthcoming guidance will supplant the existing DMC guidance, "Establishment and Operation of Clinical Trial Data Monitoring Committees," which dates back to March 2006. Notably, the title of the guidance has been modified. What distinguishes this newly issued guidance? And why the necessity for a fresh approach to DMC guidance? The subsequent articles endeavor to tackle these queries. RAPS.org FDA issues new draft guidance on data monitoring committe ..read more

It's widely acknowledged that medications for rare diseases and gene therapies come with a hefty price tag. In the United States, the FDA oversees drug approval, but there's no governmental oversight on pricing. After FDA approval, drug sponsors and manufacturers have the autonomy to propose and set the drug's price. Typically, pricing considerations revolve around factors like patient population, investment in drug development and approval, and anticipated financial gains, rather than the drug's effectiveness or its benefit-risk profile. Before this month (March, 2024), the top 10 most expens ..read more

Over the past decade, psychedelic compounds like psilocybin and ecstasy have emerged as potentially life-changing treatments for mental illnesses, including major depressive disorder and posttraumatic stress disorder. These psychedelic products may be synthetic compounds or extracts from natural products (such as magic mushroom). They usually have hallucinations effects and belongs to the substance control products.  Academics and pharmaceutical/biotech companies are now interested in developing the psychedelic products for therapeutic uses in treating diseases like major depression, PTS ..read more

ICH E9 "Addendum on Estimands and Sensitivity Analysis in Clinical Trials to the Guideline on Statistical Principles for Clinical Trials" contained discussions about intercurrent events and strategies for handling intercurrent events. Intercurrent events were defined as:  Events occurring after treatment initiation that affect either the interpretation or the existence of the measurements associated with the clinical question of interest. It is necessary to address intercurrent events when describing the clinical question of interest in order to precisely define the treatment effect that ..read more

Following the NDA or BLA approval, the sponsors may be required to conduct post-marketing studies. The phrase post marketing requirements and commitments refers to studies and clinical trials that sponsors conduct after approval to gather additional information about a product's safety, efficacy, or optimal use. Some of the studies and clinical trials may be required; others may be studies or clinical trials a sponsor has committed to conduct. Post-approval studies can be classified by FDA as a postmarketing requirement (PMR) or a postmarketing commitment (PMC).  A PMR is a study or clin ..read more

In clinical trials, analyses of the adverse events (AEs) including serious adverse events, mortality, and adverse event of special interests (AESI) are the center piece of the safety analyses. The default approach is to calculate the incidence of AEs (the number of subjects with one specific type of AE divided by the number of patients in the specific group). The presentation of the AE profiles is usually based on the incidence of AEs. For example, in an example table below, the incidence of AEs was presented for each preferred term by treatment group. The numerator is the number of subjects w ..read more

In the latest Global CardioVascular Clinical Trialists (CVCT) Workshop", one of the topics was "How to assess the disease modification in pulmonary arterial hypertension". the academic and industry representatives discussed the definition of disease modification and if the various individual drugs met the criteria as disease modifiers.  Disease modification requires that the intervention have an impact of the underlying pathology and pathophysiology of the disease. For regulatory purposes, a disease modifying effect is when an intervention delays the underlying pathological processe ..read more