CLINICAL TRIALS A BRIEF INTRODUCTIO21 sept 2010

CLINICAL TRIALS – A BRIEF INTRODUCTION:

CLINICAL TRIALS – A BRIEF INTRODUCTION ASHIM GHATAK DEPUTY DIRECTOR DIV CLINICAL & EXPERIMENTAL MEDICINE CENTRAL DRUG RESEARCH INSTITUTE LUCKNOW l

The Drug Development Process -Timelines:

The Drug Development Process -Timelines

What is a clinical trial:

What is a clinical trial A planned experiment on a human usually involving the trial of a new form of treatment

TYPES OF CLINICAL TRIALS:

TYPES OF CLINICAL TRIALS Treatment trials – to test new treatments Prevention trials – to test new approaches Screening trials – large population studies e.g. cancer detection Quality of life trials – ways to improve comfort and quality of life –cancer patients

CLINICAL TRIALS:

CLINICAL TRIALS Why do one ? Mainly to answer the question; ‘ Is treatment X better than Y?’ Main format . Controlled trial Randomized Can have designs – parallel, cross over

Clinical Trial Protocol:

Clinical Trial Protocol A detailed plan giving instructions to the study investigators (doctors) about the way to conduct the study. Contributors to the protocol development investigators, medical personnel from the Sponsor or delegated CRO representatives from the study monitoring team project statistician

Other Topics in a Study Protocol:

Other Topics in a Study Protocol Laboratories Compliance How compliance is monitored Methods used to improve compliance Organization Roles Responsibilities Budget Study Forms (CRFs) and data handling Administrative responsibilities

ETHICS:

ETHICS Is it an ethical study Is the protocol reasonable and feasible Informed consent and patient information Peer review- IRB Proper funding and management

Ethics and Safety:

Ethics and Safety Protection of the trial patient ’ s right and safety How the patient is approached for entry into the trial Regulatory obligations, including informed consent and reporting of adverse events Plan and action if a AE be detected

CLINICAL TRIAL PHASES :

CLINICAL TRIAL PHASES Phase I – in normal volunteers Phase II – in small no. of pts. Phase III- in larger clinical groups of pts –Multicentric Phase IV – post marketing surveillance

Clinical Trials:

Clinical Trials Phase 1 (volunteers) Phase 2 (patients) Phase 3 (large scale multi-centre) Phase 4 (post registration monitoring) phases can also be defined by the information you are trying to get out of the testing

Volunteer studies (phase I trials):

Volunteer studies (phase I trials) pharmacologists & employees (15-30 in number) ethical approval healthy informed consent full rescussitation + medical backup monitor single and repeat doses increase dose levels

Volunteer studies (phase I trials):

Volunteer studies (phase I trials) OBJECTIVES metabolic and excretory pathways (impinges on toxicity testing in animals) variability between individuals; effect of route; bioavailability tolerated dose range indication of therapeutic effects indication of side effects

Patient studies (phase 2 trials):

Patient studies (phase 2 trials) 150-350 ill people; informed consent needs licence maximum monitoring; full rescussitation often patients where other treatment failed OBJECTIVES: indication for use; type of patient; severity of disease; dose range, schedule and increment; pharmacokinetic studies in ill people; nature of side effects and severity; effects in special groups.

Patient studies (phase 3 trials):

Patient studies (phase 3 trials) 1500-3500 ill patients multicentre? more certain data for the objectives of phase 2 studies interactions between drugs start to become measurable in the larger population sub-groups start to be established special features and problems show up

Marketing:

Marketing getting the product right (packaging; formulation) right therapeutic slot information on new drug information for honest comparison reporting problems reporting new indications therapeutic trends

Clinical trials:

Clinical trials Drug action depends on: pharmacodynamics pharmacokinetics and dose regimen drug interactions receptor sensitivity of patient mood/personality of patient & doctor patients expectations and past experience social environment of patient clinical state of patient Clinical trial controls these variables and examines action of drug in defined set of circumstances

CLINICAL TRIALS:

CLINICAL TRIALS Other factors to consider Patient recruitment Inclusion & exclusion criteria Baseline and follow up biochemical profiles Randomization Simple Block Stratified

Three Fundamental Aspects:

Three Fundamental Aspects Which patients are eligible Which treatment are to be evaluated How each patient ’ s response is to be assessed

Specific Objectives:

Specific Objectives New treatment New indication Determine the best of a number of standard treatments To provide additional data on safety or efficacy

Methods:

Methods Hypothesis Patient population (operational definition) Inclusion Criteria Exclusion Criteria More homogeneous less generalizable!!

Design Techniques to Avoid Bias:

Design Techniques to Avoid Bias Blinding Randomization

Trial Design:

Trial Design Blinding Mechanism of treatment blinding Single, double, triple, quadruple blinding Assessment of the effectiveness of blinding Experimental design Parallel designs Cross-over designs Factorial designs Sequential designs

CRF Design:

CRF Design Identification data Research data Administrative data Regulatory data Soilker, B. Schoenfelder, J. (1991). Data Collection Forms in Clinical Trials. Racen Press, New York

Basic Information in CRF:

Basic Information in CRF Consent dates Eligibility checklist Baseline assessments Dosing of study medications ( incl. compliance) Concomitant illness Safety Effectiveness Premature termination of study

Treatment Phase:

Treatment Phase Patient management guidelines, including specifications for dose reductions, treatment delays and treatment terminations Schedules of required clinical tests and assessments

PATIENT FOLLOW UP :

PATIENT FOLLOW UP Need to monitor compliance + tt Monitor adverse events Motivate patients

Follow-up phase:

Follow-up phase Schedule of submission of required materials and data, including long-term follow-up Data and materials submission procedures

END OF TRIAL :

END OF TRIAL Completion of data recording Statistical analyses Writing up Interpretation of data Address biases New research areas and leads

Termination:

Termination Procedures for ending patients ’ participation in the trial

Closing The Study:

Closing The Study Review of clinical study reports Premature termination or suspension Archiving

Outcome Measures:

Outcome Measures Primary end points Secondary end points

Crucial Roles of Statisticians:

Crucial Roles of Statisticians Design (very important!!!) Monitoring Analysis Reporting New statistical methodology

Other Major Personnel:

Other Major Personnel Trial statistician Clinical research associate Data manager Randomization specialist Quality assurance officer Computer support personnel Resource Centre Directors Training directors Field site personnel Independent Data Monitoring Committee

Statistical Centre:

Statistical Centre Data entry and processing Ongoing monitoring of toxicity data Periodical interim analysis of study endpoints Final data analyses Preparation abstract and manuscripts

Central Laboratory:

Central Laboratory Very important role

Field Site Personnel:

Field Site Personnel Investigator/Study coordinator Research Nurse/ Participants accrual Intervention Primary data collection Follow-up

Standard Operating Procedures (SOPs) :

Standard Operating Procedures (SOPs) To ensure that the specific tasks in the trial are carried out in a consistent manner. Topics for SOPs for Investigators:

Ethics :

Ethics Initial and continuing review by ethics committees Informed consent Consent forms and information sheets

Safety Event Reporting:

Safety Event Reporting Definitions Recording and reporting AEs Recording and reporting AEs to ethics committees;

:

Thank you!

Slide 42:

THANK YOU