Principles of Clinical Research Quiz

Investigator Reporting Responsibilities

-Required to collect, assess and report all adverse events -Reported on CRF -Must report serious adverse events to sponsor and IRB immediately -Received IND safety reports from sponsor: must forward to IRB

Issues with electronic case report forms:

-adequate computer equipment -training of study staff -compliance with regulations requiring validation of computer systems

Issues with expanding overseas:

-Patients unable to afford medicines after trial discontinuation -area where trial took place is not always a market for product -study personnel must understand regulations and ethical considerations in countries where trials take place

Technology

-Remote Data Entry (RDE) -Electronic Data Capture (EDC) -Interactive Voice Response (IVR) -Internet (www.clinicaltrials.gov)

Diaries and other data collection instruments

methods for handling data collection instruments should be defined and explained in protocol

Serious adverse events in clinical trials

should be reported immediately to sponsor to ensure continued safety of subjects and to meet report requirements of FDA

Unresolved adverse events

specify time period for which any ongoing adverse events will be followed after study ends: typically 30 days, depends on drug, half-life, amount of time subject in trial, and complexity of drug and study

Event collection period

study periods during which adverse events are collected (pre-treatment vs treatment, etc.)

Expected

where specificity and severity are consistent with info in investigator brochure or labeling

Adverse Event: ICH definition

-"any untoward medical occurrence in a patient or research subject administered a pharmaceutical product" -Any unfavorable and unintended sign, symptom, or disease temporarily associated with use of product"

Advantages of IVR

-24 hour data collection -automated data collection eliminates transcription errors and interviewer mistakes -can eliminate need for some visits

Serious Adverse Event (SAE)

-Adverse event that results in: death or life threatening (immediately as it occurred), requires hospitalization (or prolongation of hospitalization if already in hospital), persistent or significant disability or incapacity, congenital anomalies or birth defects -or that the investigator or sponsor judges as serious -or defined as serious according to regulatory agency in country where event occurred

Electronic Case Reports Forms (eCRFs)

-Data entered directly into computer and downloaded to sponsor/CRO -Eliminate data entry step required of paper CRF -Provides immediate feedback to site: queries

Remote Data Entry (RDE)

-Data that are captured by the site and then transmitted to sponsor/ CRO -2 Methods: Paper CRFs competed at site and then faxed, electronic CRFs or electronic data capture (EDC)

FDA adverse event reporting system (FAERS)

-FDA database of reported adverse events and med error reports -supports FDA post-marketing surveillance of drugs and biologics -evaluated by clinical reviewers in CDER/CBER to monitor safety of approved products

ICH GCP Section 4.11 Safety reporting

-all serious adverse events should be reported immediately to sponsor: exceptions are designated in protocol or investigator's brochure as not necessary to report immediately -initial report should be followed by a detailed, written report -investigator should comply with reporting unexpected serious adverse events to authorities and IRB

Anticipated Benefits of Pharmacogenomics

-better, safer drugs the first time -more powerful medicines -more accurate methods of determining appropriate drug dosages -advanced screening for disease -better vaccines -improvements in drug discovery and approval process -decrease in overall cost of healthcare

Barriers to pharmacogenomics

-complexity of finding gene variations that affect drug response -limited drug alternatives -disincentives for pharma companies to make multiple pharmacogenomics products -educating healthcare providers

Sources of adverse events

-directly observed -elicited from subject by means of general, non-directive question -spontaneously volunteered by subject -Lab, EKG, other tests

exposure in utero

-instruction for reporting and subsequent outcome of pregnancy -required to follow until child is born or pregnancy is terminated -no visit requirement, just contact periodically

Expanding clinical trials to overseas

-less cost due to low patient recruitment and operating costs -feature sizeable group of patients with conditions being studied -important markets for new medicines -Emerging markets: Asia, Latin America, and Africa

How does EDC and RDE affect monitoring?

-less monitoring visits -more virtual monitoring when applicable

Smart pill

-micro chip embedded pills which activate by stomach acid to transmit data -silicone and metal sponsor transmits data via faint radio signal to patch on patient's skin -then transmits it to smartphone, email, etc

sponsor reporting responsibilities

-must review safety data throughout trial -must report related and unexpected serious adverse events: to FDA within expedited timeframe, inform all investigators -if serious adverse event requires trial termination, all investigators and subjects must be notified as well as IRB

Spontaneous Adverse Events

-reported spontaneously/voluntarily to sponsor by medical professionals, patients, or others (versus being reported systematically during clinical trials -classified as "related" to drug for reporting purposes -most reports from medical professionals

21 CFR 312.64 Investigator Reports

-requires investigators to report adverse events -safety reports: investigator shall promptly report any adverse events that may be caused by or probably caused by the drug -By signing 1572, investigator agrees to report adverse events

FDA requirement on reporting serious adverse events

-sponsors must report unexpected serious adverse events that are fatal or life-threatening: by phone or fax, within 7 days of date of becoming aware, written report sent to FDA within 15 days becoming aware of event -sponsors must report unexpected serious adverse events that are not fatal or life-threatening: in writing, within 15 days of becoming aware

Pharmacogenomics

-the study of how an individual's genetic inheritance affects body's response to drugs -Pharmacology + Genomics -Drugs may one day be tailor-made for individuals adapted to their specific genetic make-up: key to personalize drugs with greater safety and efficacy

Regulatory actions of safety concerns by FDA

-updated labeling requirements -restricting use -communicating new safety info to public -removing a product from market

Interactive Voice Response (IVR)

Automated acquisition and dispersal of information: converges computer-automated interviewing with touchtone phone service

Adverse Drug Reaction: In approved products

All noxious and unintended responses to a drug at doses normally used for prophylaxis, diagnosis, or therapy of a disease or modification of physiological function

Result of outsourcing

CRO business will continue to grow and sponsor

Adverse Drug Reaction: In preapproved clinical experience

all noxious and unintended responses to medicinal product related to any dose

significant disability

causes substantial disruption to person's normal life and activity

timely notification

define when investigator must report adverse events and serious adverse events to sponsor

CFR Title 21 Part 11

governs use of electronic records

Who can report adverse events to the FDA?

healthcare professionals, patients

life-threatening

patient is in immediate danger of death unless intervention is done

Related to or associated with drug

reasonable possibility that even could have been caused by investigational product

Nonserious adverse events in clinical trials

recorded on CRF's and collected by CRA during monitoring visits

Classifications of adverse events in a clinical trials?

serious, related, and unexpected