clinical trials – phase iii. what are phase iii trials confirmatory phase (therapeutic...

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