Personalized trials and outcome measures Flashcards
Describe genotypic characteristics of tuberous sclerosis complex.
- Autosomal dominant
- Gene mutation (often ‘de novo’)
- Mutated genes (TSC1 and TSC2) are tumor suppressor genes (inhibit mTOR)
What is an advantage to drug-repurposing?
Decrease the time and costs (because of use of existing data and known safety)
Tuberous sclerosis complex is characterized by a variety of symptoms. Some of these symptoms can not be treated, but some can. E.g. the behavioural problems that are associated with TBC.
What repurposed drug could aid in reducing the behavioural problems of TBC?
Cannabidiol (CBD)
Name three types of RCT trial designs.
- Parallel group
- Crossover
- N-of-1
Describe the characteristics of a N-of-1 design.
A prospectively planned randomized, controlled multiple-crossover trial to determine the effectiveness of an intervention in a participant.
- Comparators may include placebo, usual care, alternate treatment or no intervention.
What characteristics/advantages does an N-of-1 trial have when there’s strong methodology?
- Diverse and small population (increasing power due to crossing-over multiple times)
- Optimal treatment for individual
- Effectiveness at population level
- Shortening time lag (identification -> implementation of evidence-based treatment)
- Heterogeneity (within and between patietns)
What is deep phenotyping?
The precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described.
What is the relation between deep phenotyping and personalized medicine?
The emerging field of personalized / precision medicine aims to provide the best available care for
each patient based on stratification into disease subclasses with a common biological basis of
disease
What is the definition of an outcome measure and what purpose do these outcome measures serve?
- Outcome measure → measurement or endpoint to assess the effect of a treatment
- Purpose → monitoring patient status, determining the effect of intervention, monitoring an intervention.
There are three types of outcome measures:
- Hard
- Surrogate
- Patient-related
What is the definition of these types?
- Hard → diagnoses, morbidity, e.g. myocardial infarction, CVA
- Surrogate → easily measurable variable, e.g. laboratory assessments, often not direct measure of clinical effect
- Patient-related → symptoms, quality of life
Why are outcome measures important?
- Objectively measurable (intervention / natural course)
- Valid and reliable
- Continuous, even with changes in practitioner
- Prevention of overtreatment and undertreatment
- Decision-making
- Acknowledging treatment (ZIN, CBG, EMA etc)
What are things to take into consideration when choosing an outcome measure?
- Type of outcome measure
- Acceptance & user-friendly
- Measurement properties (validity, reliability, responsiveness to change)
- Relevance (is effect statistically and/or clinically/socially relevant?)
There are 5 levels of outcome measures. Name these.
- Biological and physiological factors
- Symptoms
- Functional status
- General health perceptions (subjective)
- Overall quality of life
What’s a definition of a biomarker?
A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic
processes, or pharmacologic responses to a therapeutic intervention.
What is the difference between a biomarker and a clinical endpoint?
A clinical endpoint is the subject’s health and well-being from the subject’s perspective. A biomarker is an objective, quantifiable characteristic of a biological process and thus not necessarily correlate with a patient’s experience and sense of well-being.
How do valid biomarkers contribute to clinical research?
- Delineation of events between exposure and disease
- Establishment of dose-response
- Identification of early events in the natural history
- Identification of mechanisms by which exposure and disease are related
- Reduction in misclassification of exposure or risk factors and disease
- Establishment of variability and effect modification
- Enhanced individual and group risk assessments
What determines the quality of a patient-reported outcome measure?
- Reliability
- Responsiveness
- Validity
What is the Health-Related Quality of Life (HRQOL)?
A PRO containing physical symptoms, functional status, consequences of a disease on psychological and sociological functioning.
What is value-based healthcare?
Health care that aims for a high value for patients. Results should be assessed by what is important to patients.
What is the importance of PRO(M)s in regard to:
- healthcare
- quality registration
- research
What is Goal Attainment Scale (GAS)?
GAS is a individualized outcome measure involving goal selection and goal scaling that is standardized in order to calculate the extent to which a patient’s goals are met.
What are advantages and disadvantages of Goal Attainment Scaling (GAS)?
Advantage:
- Sensitive instrument that can be used for heterogeneous patient populations
- Patient is involved with treatment
Disadvantage:
- Labor intensive
- Validation is complex
- Unclear for neuropsychiatric goals
In regard to Goal Attainment Scaling (GAS), what is important to take into consideration regarding the goals that are set?
The goals set should be:
- SMART (Specific, Objectively measurable, Acceptable, Realistic, Time-related)
- Important to the patient
- Related to the intervention
Yes or No, is this statement related to the WMO?
Quality analysis of different laboratory instruments with the aim of researching
the possibility of switching to a cheaper instrument.
No
Yes or No, is this statement related to the WMO?
Questionnaire about sexuality in students between 18 – 25 years old
Yes
Yes or No, is this statement related to the WMO?
Patients with TSC have to maintain a daily seizure diary.
Yes
Yes or No, is this statement related to the WMO?
In a study on the prevention of decubitus, subjects are randomized to the use
of mattress A or B in their bed.
No
Yes or No, is this statement related to the WMO?
Research on the configurations and conditions of MRI to visualize certain
organs.
No
Yes or No, is this statement related to the WMO?
CBD study in patients with TSC.
Yes
What are the challenges and pitfalls of N-of-1 trials?
- Generalizability
- Recruitment
- Treatment complianse
- Documentation
- Medication
- What if the treatment is effective?
