TRANSLATIONAL RESEARCH ALONGSIDE CLINICAL TRIALS Flashcards
WHAT IS TRANSLATIONAL RESEARCH?
- THE TRANSLATION FROM BASIC SCIENCES TO HUMAN STUDIES
- TRANSLATING KNOWLEDGE GAINED FROM LABORATORY SCIENCE INTO CLINICAL PRACTICE TO IMPROVE HEALTH
‘BENCH-TO-BEDSIDE’
Translational research is research aimed at translating results in basic research into results that directly benefit humans.
AIMS OF TRANSLATIONAL RESEARCH IN MEDICINE
PRODUCE NEW:
- TOOLS FOR DIAGNOSING DISEASE
- MEDICAL DEVICES
- PREVENTION METHODS
- THERAPEUTICS
THE ‘VALLEY OF DEATH’?
The gap between development activity and commercial use (academia and industry)
Development in science/medicine goes through:
BASIC SCIENCE –> TRANSLATIONAL SCIENCE –> CLINICAL SCIENCE
- ALTHOUGH MANY SCIENTIFIC DISCOVERIES LOOK PROMISING IN THE BEGINNING, THEY OFTEN FAIL IN THE TRANSLATIONAL PHASE (DUE TO E.G. LACK OF FUNDING, NOT ENOUGH RELEVANCY TO HUMAN DISEASE), SO THEY REMAIN IN THE SO CALLED ‘VALLEY OF DEATH’
PERSONALISED HEALTHCARE
TREATING THE RIGHT PATIENT WITH THE RIGHT TREATMENT IN THE RIGHT TIME
- ADDRESSES TRATMENT HETEROGENITY (DIFFERENT PATIENTS RESPOND DIFFERENTLY TO TREATMENTS)
- HELPED BY INCREASED AVAILABILITY OF MOLECULAR PROFILING DATA, INCORPORATING BIOMARKERS INTO CLINICAL TRIALS, STRATIFYING PATIENTS
BIOMARKER DEFINITION?
A DEFINED CHARACTERISTIC THAT IS MEASURED AS AN INDICATOR OF NORMAL BIOLOGICAL PROCESSES, PATHOGENIC PROCESSES, OR RESPONSES TO AN EXPOSURE OR INTERVENTION, INCLUDING THERAPEUTIC INTERVENTIONS
- NOT AN ASSESSMENT OF HOW A PATIENT FEELS, FUNCTIONS OR SURVIVES
TYPES OF BIOMARKERS
- DIAGNOSTIC (USED TO DETECT OR CONFIRM PRESENCE OF DISEASE)
- MONITORING (MEASURED SERIALLY FOR ASSESING STATUS OF A DISEASE OR FOR THE EVIDENCE OF EXPOSURE)
- PHARMACODYNAMIC/RESPONSE (MEASURED BIOLOGICAL RESPONSE TO A MEDICAL PRODUCT OR ENVIRONMENTAL AGENT) E.G. ASSESS REPSONSE TO DRUGS
- PREDICTIVE (USED TO IDENTIFY INDIVIDUALS WHO ARE MORE LIKELY THAN SIMILAR INDIVIDUALS WITHOUT THE BIOMARKER TO EXPERIENCE A FAVOURABLE OR UNFAVOURABLE EFFECT FROM EXPOSURE TO A MEDICAL PRODUCT OR AN ENVIRONMENTAL AGENT) E.G. DETERMINE IF PATIENT IS LIKELY TO RESPOND TO A THERAPY
- PROGNOSTIC (TO IDENTIFY LIKELIHOOD OF A CLINICAL EVENT, DISEASE RECURRENCE OR PROGRESSION IN PATIENTS WHO HAVE A SPECIFIC DISEASE)
- SAFETY (MEASURED BEFORE OR AFTER AN EXPOSURE TO A MEDICAL PRODUCT OR AN ENVIRONMENTAL AGENT TO INDICATE THE LIKELIHOOD, PRESENCE, OR EXTENT OF TOXICITY AS AN ADVERSE EFFECT) E.G. MONITORING FOR EXCESSIVE DRUG TOXICITY
- SUSCEPTIBILITY/RISK (A BIROMARKER THAT INDICATES A POTENTIAL FOR DEVELOPING A DISEASE IN AN INDIVIDUAL WHO DOES NOT CURRENTLY HAVE A CLINICALLY APPARENT DISEASE) E.G. IDENTIFY INDIVIDUALS WHO ARE PREDISPOSED TO DEVELOP A DISEASE
2 MAIN TYPES OF BIOMARKERS USED IN CLINICAL TRIALS?
- PROGNOSTIC (PREDICTS HOW A DISEASE MAY DEVELOP/PROGRES IN AN INDIVIDUAL REGARDLESS OF THE TYPE OF TREATMENT, FOCUSES ON THE CLINICAL OUTCOME)
- PREDICTIVE (PROVIDES AN INDICATION OF THE PROBABLE EFFECT OF TREATMENT ON PATIENT)
–> PROGNOSTIC BIOMARKERS CAN BECOME PREDICTIVE IN THE FUTURE AND SOME BIOMARKERS CAN BE BOTH PREDICTIVE AND PRGNOSTIC
WHAT CAN BIOMARKERS FACILITATE IN CLINICAL TRIALS?
- CAN ALLOW FOR STRATIFICATION/classification OF PATIENTS INTO SUBGROUPS
- BIOMARKER POSITIVE (MARKER PRESENT)
- BIOMARKER NEGATIVE (MARKER ABSENT)
DIFFERENCE OR RATIO OF TREATMENT EFFECTS IN BIOMARKER POSITIVE COMPARED TO BIOMARKER NEGATIVE GROUPS IN CLINICAL TRIALS IS CALLED:
INTERACTION
DESCRIBE DISCORDANT RISK RANDOMISATION DESIGN IN BIOMARKER TRIALS?
- CLINICAL RISK AND BIOMARKER RISK ARE COMPARED
- IF THEY DO NOT MATCH (I.E. AREN’T CONCORDANTLY HIGH OR LOW), AND THE RISK IS DISCORDANT, THAT GUIDES THE RANDOMISATION
DESCRIBE THE INERMEDIATE RISK RANDOMISED DESIGN IN BIOMARKER TRIALS?
- PATIENTS ARE GROUPED BASED ON BIOMARKER-BASED RISK
- LOW, INTERMEDIATE OR HIGH RISK
- INTERMEDIATE RISK GUIDES RANDOMISATION (E.G. HIGH RISK GROUPS GETS TREATMENT, LOW RISK GROUP DOESN’T, AND INTERMEDIATE IS RANDOMLY SPLIT SO A PART GETS TREATMENT AND A PART DOESN’T)
DESCRIBE THE RANDOMISE-ALL DESIGN IN BIOMARKER TRIALS?
- PATIENTS ARE RANDOMISED TO EITHER THE STANDARD OF CARE OR THE EXPERIMENTAL APPROACH
- WITHIN BOTH OF THOSE GROUPS, PATIENTS ARE THEN ASSESSED FOR THEIR BIOMARKER SIGNATURE AND ALLOCATED TO EITHER BIOMARKER + OR BIOMARKER - GROUP
- ALLOWS US TO MAKE SEVERAL COMPARISONS IN EACH OF THE 2 GROUPS
DESCRIBE THE INERACTION DESIGNED, AKA BIOMARKER-STRAIFIED DESIGN IN TRIALS?
- PATIENTS ARE FIRST ASSESSED FOR THEIR BIOMARKER SIGNATURE AND STRATIFIED (GROUPED) ACCORDINGLY
- WITHIN EACH OF THOSE 2 GROUPS, PATIENTS ARE THEN RANDOMISED TO EITHER STANDARD CARE OR EXPERIMENTAL CARE
DESCRIBE THE BIOMARKER-BASED STRATEGY DESIGN WITH STANDARD CONTROL IN TRIALS?
- PATIENTS ARE RANDOMISED TO EITHER BIOMARKER-BASED STRATEGY OR NON-BIOMARKER BASED STRATEGY
- NON BIOMARKER BASED STRATEGY GROUP IS OFFERED THE STANDARD OF CARE
- THE BIOMARKER BASED STRATEGY PATIENTS ARE THEN ASSESSED FOR THEIR SIGNATURE (BIOMARKER + OR -) AND ARE THEN ALLOCATED TREATMENT BASED ON THEIR SIGNATURE (- GET STANDARD, + GET EXPERIMENTAL)
DESCRIBE THE TARGETED (SELECTION) DESIGN IN BIOMARKER TRIALS?
- PATIENTS ASSESSED FOR BIOMARKER SIGNATURE
- BIOMARKER NEGATIVE PATIENTS TAKEN OFF THE STUDY
- BIOMARKER POSITIVE PATIENTS ARE THEN RANDOMISED BETWEEN THE STNDARD AND EXPERIMENTAL TREATMENT
