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Placebos and Blinding in Randomized Controlled Cancer Clinical Trials for Drug and Biological Products Guidance for Industry

FinalCenter for Drug Evaluation and Research Center for Biologics Evaluation and Research08/29/2019
Blinding

Description

This guidance provides recommendations to industry about the use of placebos and blinding in randomized controlled clinical trials in development programs for drug or biological products to treat hematologic malignancies and oncologic diseases. This guidance does not address the statistical analyses that can be considered when data are unblinded in these trials.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

4
placebo

placebo is given as monotherapy

Combination Product

Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.

Biological Product

Regulated under section 351(i) of the PHS Act; Virus, therapeutic serum, toxin, vaccine, or protein applicable to prevention or treatment; Alternative regulation category for products meeting device definition

Drug Product

RTRT and CTD sections apply to drug products

Stakeholders

2
investigator

facilitate discussions between a prospective subject and an investigator; Responsible for conducting research and providing informed consent

Sponsor

Entity responsible for submitting applications under section 524B

Regulatory Context

Regulatory Activities

1
Randomized Controlled Clinical Trials

development programs for drug or biological products

Document Types

3
statistical analysis plan

Basic statistical principle for clinical trials

protocol

Submitted to an existing active IND

informed consent document

Document required for patient participation; document describing risks, benefits, and procedures to the patient

Technical Details

Substances

8
corticosteroids

primary adverse event prophylaxis

acetaminophen

primary adverse event prophylaxis

antihistamine

primary adverse event prophylaxis

Infliximab

treatment for adverse events

Interleukin-6 Antagonist

treatment for adverse events

Cyclophosphamide

Positive control substance used in the assay; positive control used with S9 metabolic activation

Glucocorticoids

Circulating hormones produced by the adrenal gland.; Used as rescue therapy for adrenal insufficiency

Placebo

Accountability procedures for the investigational product including placebo; used as a reference in a clinical trial

Processes

3
Sham Surgical Procedure

setting where justification for trial design is important

Adjuvant Therapy

trials where standard of care is surveillance

Maintenance Therapy

trial design where placebo-controlled study may be useful

Clinical Concepts

7
adverse event

Reason a patient may be unable to complete a PRO measure; Treatment discontinuation due to AE.; Reason for treatment discontinuation or PRO non-completion.

progression

maintenance of blinding at the time of disease progression

disease recurrence

determination of disease recurrence for DFS

infusion reaction

prevent infusion reaction

Serious Adverse Events

SAEs collected during interventional clinical trials

Oncologic Diseases

Treatment of oncologic diseases

Hematologic Malignancies

bone marrow biopsies in patients with certain malignancies

Identified Hazards

Hazards

1
Investigator Bias

concern in open-label comparative trials

Standards & References

External Standards

1
WMA Declaration of Helsinki

Ethical principles for medical research involving human subjects

ICH References (1)

ICH E10

Choice of Control Group in Clinical Trials.

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)

Placebos and Blinding in Randomized Controlled Cancer Clinical Trials for Drug and Biological Products Guidance for Industry | Guideline Explorer | BioRegHub