Clinical Trials 4

8/3/2019 Clinical Trials 4

1/22

PHASE IV STUDIES

-D.SAIKRISHNA


2/22


3/22

Introduction

Also known as Post Marketing Surveillance Trial.

Phase IV trials involve the safety surveillance(pharmacovigilance) and ongoing technical support of a drugafter it receive permission to be sold.

Phase IV studies may be required by regulatory authorities ormay be undertaken by the sponsoring company forcompetitive or other reasons (for example, the drug may nothave been tested for interactions with other drugs, or oncertain population groups such as pregnant women, who areunlikely to subject themselves to trials).

The safety surveillance is designed to defect any rare or long-term adverse effects over a much larger patient populationand longer time period than was possible during the Phase I-IIIclinical trials.


4/22

Introduction

Harmful effects discovered by Phase IV trials may resultin a drug being no longer sold, or restricted to certainuses: recent examples involve cerivastatin (brand names

Baycol and Lipobay), troglitazone (Rezulin) and rofecoxib(Vioxx).

Companies also may evaluate different formulations of adrug (like sustained release).


5/22

Driving Forces.

Commercial:comparison with existing marketleader, trying new dosage forms and formulations

Regulatory: fulfillment of post-approval regulatory

commitment Academic: developing correlations with new

diagnostic techniques or biomarkers, studying drug-drug interactions, experiences with the population

that is unlikely to participate in clinical trials Safety: identifying new side effects,

contraindications

Efficacy: identifying new indications


6/22

Information gathered from Phase

4 Clinical Trials Overall morbidity and mortality in very large

sample of the patient population

The place for the product in complex treatment

algorithms where many alternative therapiesmay be possible in countless combinations

Overall cost-effectiveness in routine medicalpractice, without the intensive interventions of apreauthorization study

The incidence of rare suspected adversereactions or specific benefits in patient sub-groups

Compliance in routine medical practice


7/22

Seeding Studies

Seeding studies are planned more for marketingadvantage than for a specific scientific reason.

Their prime aim is to alter physician prescribing, and

since this objective is nowhere mentioned in theprotocol, such studies are held in very low esteem

Regulatory authorities do not support the conduct ofseeding studies that masquerade as Phase IV studies

Such studies lack in control group, statistical power,safety and efficacy aim

Such studies involve marketing representatives thatclinical researchers


8/22

Quality of Life and

Pharmacoeconomic Studies QOL studies have been made mandatory by

FDA

Drug abuse and drug dependencies arestudied extensively in post-approval phase ofresearch

Cost of therapy can be studied widely in the

post- approval phase since the productbecomes commercially available

Cost of therapy can be compared with thecost of the existing therapy


9/22

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


10/22

Periodic Safety Update

ReportsSubsequent to approval of the product, new drugsshould be closely monitored for their clinical safetyonce they are marketed. The applicant shall furnishperiodic safety update reports (PSURs) in order to:

Report all the relevant new information fromappropriate sources

Relate these data to patient exposure

Summarize the market authorization status in

different countries and any significant variationrelated to safety

Indicate whether changes should be made toproduct information in order to optimize the use ofthe product


11/22

Periodic Safety Update

Reports Ordinarily all dosage forms and formulations as well

as indications for new drugs be covered in onePSUR.

Within the single PSUR separate presentation ofdata for different dosage forms, indications orseparate 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


12/22

Classical phase IV research

Different chemical entities offering similar efficacyand 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 thenew drugs in post marketing surveillance

New indication: Aspirin, and sildenafil are classicalexamples

New dosage regimen: optimization of dosageregimen is possible with greater exposure


13/22

Categories of phase IV

studiesDescriptive Studies: Provide information on pattern of disease

occurrence in populations according to

demographic and prognostic characteristics. Data used are routinely collected epidemiologic

intelligence with is analyzed to identify theoccurrence of rare adverse reaction or togenerate a hypothesis.

Passive monitoring of events and reports is animportant method for collecting data included indescriptive studies.


14/22

Categories of Phase IV

StudiesCross- sectional Studies: They are also called as surveys or prevalence

studies that involve a statistically based random

sampling of a target population. Data are classified according to reported

exposure to medicines and observed outcomes.

Results pertain to a single point in time, and thistype of study is therefore like a snapshot in time.

If conducted retrospectively, it may be unclearwhether exposure truly preceded the outcome.


15/22


StudiesCase- control studies: They are always retrospective studies where

cases have the disease and controls do not.

Data are collected by looking backward in timeto determine differences between the twogroups in the past.

Cases matched for confounding factors (e.g.,age, sex) with one or more controls.

Such studies may involve bias because of theirnature yet generate important data especiallyincidence.


16/22


StudiesCohort Studies: A Cohort is a group that is exposed, and followed

forward to a point in time when its members areevaluated retrospectively to look for differences inthe frequency of one or more outcomes from acontrol unexposed group.

If the case and controls both come from the samestudy population, the results of the study are more

easily validated. It is imperative to ensue that both cases and controls

are free from disease at the start of the observationperiod.


17/22


StudiesControlled clinical trials Comparison made with controlled

Mostly carried out by Pharmaceuticalcompanies

Purpose is regulatory, commercial and safetyin the post approval phase of drug

development. Most validated hence more reliable

Statically very sound


18/22


StudiesObservational studies

Records specific events that are occurring in a

defined population without any interventionby the researcher


19/22

Phase IV studies are conducted to

Address unanswered questions arose duringPhases 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 toconfirm its efficacy and better understand itssafety


20/22

Determine if results obtained at tertiary careand excellent hospitals during Phase I-III canbe confirmed in other hospitals as well aswhen medicine is used by larger number ofnew physicians.

Evaluate whether any rare but serious

adverse reaction occur, or if the drug is acandidate for being abused


21/22

Evaluate the pattern of a medicines

utilization in a specific or general populations.

Study the clinical characteristics of over-dosage and the means of counteracting thisproblem

Assess the costs of adverse reactions to

various sectors of society and develop themeans to meet theses costs.


22/22

THE END

Date post:	06-Apr-2018
Category:	Documents
Upload:	bob-bin
View:	222 times
Download:	0 times

Clinical Trials 4

Documents