CLINICAL TRIALS – PHASE III

What are phase III trials  Confirmatory phase (Therapeutic confirmatory trial)  Trials are done to obtain sufficient evidence about efficacy and safety  Conducted in larger number of patients  In comparison with standard drug/placebo

OBJECTIVES  To establish efficacy of the drug against existing therapy  To establish the safety in relatively large number of patients  To establish method usage in clinical practices  To identify contraindications, warnings

SUB-TYPES  Phase III a Before submission of NDA  Phase III b After submission of NDA but before approval

STUDY- SITES  Conducted at community hospitals  Other facilities Nursing home Private clinics  Multicentric  High costs involved

AGREEMENTS  Agreements with investigator (time lines, responsibilities, financial support, archives, publication of results etc)  Agreements with laboratories (time lines, costs, quality)  Agreements with hospitals (for use of facilities and payments if any  Agreements with courier companies for shipments

STUDY POPULATION  Patients with target disorder  Patients for whom drug may be indicated  Number of patient upon Statistical requirement Availability of patients Regulatory requirements depends Avoid patient with severe medical conditions

STUDY DESIGN  Need of study design in phase III  Randomization  Blinding  Control Control is needed to have comparison of test drug with other A- Active control B- Placebo control

CONTD…  Inclusion criteria is more flexible as large number of patients are recruited COMPLIANCE  Should noncompliant patients be discontinued from study ?

ESSENTIAL DOCUMENTS  Trial Protocol with identifiable date and version  Informed consent form with translations and back translations  Case Record Forms  Brochures- Investigators and Patients  Patient recruitment aids

SITE PREPARATIONS  Ensure that IRB exists and functions as per regulatory requirements  Ensure personnel are adequately trained, both in technology and GCP  Collect all documents pertaining to the site eg.  CVs of investigators  Conflict of Interest Forms  Training certificates if required

TRIAL MANAGEMENT  Manage supply of trial related documents, trial supplies  Recruitments schedules and time lines  Co-ordination with laboratories  Timely receipt and completion of CRFs  Resolution of queries  Payment to sites

PATIENT VISIT  Patient visits should be as per visit schedule  Match patient visits with logs  Deviations are followed up  Remedial action identified and communicated  Patient withdrawals- identify and remedy the causes

INITIATION MEETING  Held after all trial material reaches sites  Held on site or by phone or video conference  Discuss all procedures again  Confirm total understanding and availability of trial material  If all is clear declare site open for recruitment

Monitoring  To check/watch study  To evaluate progress of trial  To check compliance with SOPs, Protocol and Regulatory requirements  If any fault that should be brought in notice of sponsor

INVESTIGATORS MEETING  Held after all documents are complete  To be attended by Investigator’s and co-ordinators  Discuss protocol, ICF administration, CRF entry, randomization and recruitments, trial procedures, financial agreements and any study related activities

AUDITING  To check compliance with protocol, SOP’s, and GCP  Observation and finding of auditor should be documented  Auditors may audit GMP conditions under which the drug was manufactured  Auditors may audit electronic systems for compliance with 21CFR 11.

CLOSE OUT  After ensuring the study is complete.  All CRF received  All study material is accounted for  All investigational product is accounted for and balance returned to sponsor  Ensure payment completion

TIME PERIOD & FEE  Study generally lasts anywhere from 2 to 10 years (with an average length of 5years)  According to Sch. Y the fee required for Phase III is Rs.25000