Phase Iv Studies: - D.Saikrishna
Phase Iv Studies: - D.Saikrishna
Phase Iv Studies: - D.Saikrishna
-D.SAIKRISHNA
Introduction
Also known as Post Marketing Surveillance Trial. Phase IV trials involve the safety surveillance
(pharmacovigilance) and ongoing technical support of a drug after it receive permission to be sold. Phase IV studies may be required by regulatory authorities or may be undertaken by the sponsoring company for competitive or other reasons (for example, the drug may not have been tested for interactions with other drugs, or on certain population groups such as pregnant women, who are unlikely to subject themselves to trials). The safety surveillance is designed to defect any rare or longterm adverse effects over a much larger patient population and longer time period than was possible during the Phase I-III clinical trials.
Introduction
Harmful effects discovered by Phase IV trials may result
in a drug being no longer sold, or restricted to certain uses: recent examples involve cerivastatin (brand names Baycol and Lipobay), troglitazone (Rezulin) and rofecoxib (Vioxx). Companies also may evaluate different formulations of a drug (like sustained release).
Driving Forces.
Commercial: comparison with existing market
leader, trying new dosage forms and formulations Regulatory: fulfillment of post-approval regulatory commitment Academic: developing correlations with new diagnostic techniques or biomarkers, studying drugdrug interactions, experiences with the population that is unlikely to participate in clinical trials Safety: identifying new side effects, contraindications Efficacy: identifying new indications
Seeding Studies
Seeding studies are planned more for marketing
advantage than for a specific scientific reason. Their prime aim is to alter physician prescribing, and since this objective is nowhere mentioned in the protocol, such studies are held in very low esteem Regulatory authorities do not support the conduct of seeding studies that masquerade as Phase IV studies Such studies lack in control group, statistical power, safety and efficacy aim Such studies involve marketing representatives that clinical researchers
studied extensively in post-approval phase of research Cost of therapy can be studied widely in the post- approval phase since the product becomes commercially available Cost of therapy can be compared with the cost of the existing therapy
Study Design
Generally open label randomized studies
Market leader is used as comparator instead
of placebo Study population is very less restricted to reach close to the routine clinical practice They may involve 300 to 3000 patients They are long term studies to study long term safety profile of the drug
as indications for new drugs be covered in one PSUR. Within the single PSUR separate presentation of data for different dosage forms, indications or separate population need to be given. All relevant clinical and non-clinical safety data should cover only the period of the report. The PSURs shall be submitted every six months for the first two years after approval. For subsequent two years the PSURs need to be submitted annually
and safety profiles: research work for differentiation Medicines within the same pharmaceutical class: research work to identify the best amongst the lot Demonstration of efficacy in different patient groups: different patient groups get exposed to the new drugs in post marketing surveillance New indication: Aspirin, and sildenafil are classical examples New dosage regimen: optimization of dosage regimen is possible with greater exposure
Phases I,II,III Continue clinical trial initiated but not completed during Phase III Investigate interactions of new drugs Expose more patients to the new drug to confirm its efficacy and better understand its safety
Determine if results obtained at tertiary care and excellent hospitals during Phase I-III can be confirmed in other hospitals as well as
when medicine is used by larger number of new physicians. Evaluate whether any rare but serious adverse reaction occur, or if the drug is a candidate for being abused
dosage and the means of counteracting this problem Assess the costs of adverse reactions to various sectors of society and develop the means to meet theses costs.
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