Clinical trial phases – Phases 4 and 5

Clinical trial phases - Phases 4 and 5 1 Medicine Made Easy Research
Upon authorization by the FDA and EMA, therapies determined to have proven safety, efficacy and quality may be made available to the general population. Patients and their physicians have expectations of benefit. However, not all safety or efficacy issues have been determined. The FDA and EMA require continued evaluation after release to evaluate safety signs that may affect the benefit-risk ratio.

These Phase IV studies include “all studies (other than routine surveillance) performed after drug approval and related to the approved indication”.

These are post-marketing surveillance studies. The focus of the trials is on how drugs work in the real world. Anyone seeking treatment from their physician may be treated with the therapy. Their personal physician monitors the results of the treatment.

Efficacy and detection of rare or long-term adverse effects over a much larger patient population and longer time period are evaluated, healthcare costs and outcomes are determined, and pharmacogenetics is studied. New clinical indications for a drug may be established and a large number of patients and physicians involved.

The FDA and EMA may require that a developer conduct a Phase IV trial as a stipulation for drug approval. Less than half of the studies are completed or even initiated by developers.

Phase IV trials may result in a drug being removed from the market or restricted to certain indications.

History and outcome

Initially, these trials were run much like Phase III studies and were conducted for marketing purposes. Studies were done at institutions with investigators familiar with clinical trials and had inclusion and exclusion criteria similar to those of Phase III studies. Results did not reflect what would happen under normal conditions. As a result, innovative studies were designed to involve ordinary physicians in naive research communities.

Goals have been broadened and include evaluation of specific pharmacological effects, establishing the incidence of adverse reactions, determining effects of long-term administration of a therapy, establishing a new clinical indication for the therapy, evaluation of the therapy in higher-risk populations, etc.

A main issue of concern is the mix of medical research and clinical practice.

Adverse drug reactions

Reported serious adverse drug reactions submitted to the FDA’s Med Watch program have increased from 150,000 in 2000 to 370,000 in 2009. EMA has received 91 834 reports in 2009 with no comparison for the period. Physicians and consumers or drug manufacturers submit these reports.

Criticisms have included reliance on voluntary reporting of adverse events, trust in drug manufacturers to collect/evaluate/report drug safety data that may risk financial interests, and dependence on one government body to approve a drug and then require studies that might lead to withdrawal from the market.

Proffered solutions have included large-scale simple RCTs with few eligibility and treatment criteria, preplanned metaanalyses of a series of related trials, and establishment of a national health data network to evaluate post-marketing surveillance independent of the FDA and EMA approval processes.

Phase V clinical trials

This translational research is designed to “move from bench to bedside”.

Phase V clinical trials refer to comparative effectiveness research and community-based research.

  • Research is done on data collected.
  • All reported uses are evaluated.
  • Patients are not monitored.
  • Its main focus is to determine the integration of a new therapy into widespread clinical practice.
  • Filed under:
    • Cornell cooperative extension
    • Evidence-based living
    • Policy
  • The learning center tagged with:
    • Cooperative Extension programs
    • Evaluation
    • Evidence-based programs
    • Research methods
    • Research translation.

The final outcome of clinical trials is improved clinical medicine. Understanding the steps to bring a new therapy to the general population provides clinicians insight into their staged development and timeline to availability. By improving developmental strategies and studies, time to availability.

Source: Mahan, V.L. (2014) Clinical Trial Phases. International Journal of Clinical Medicine, 5, 1374-1383.

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