Personalized trials and outcome measures

Question 1

How can one investigate challenges in investigational research in rare genetic disorders and how can one overcome these?

Answer 1

• Diverse and small population
  ▪ Increasing power (crossing-over multiple times)
• Heterogeneity - generalisability
  ▪ Within patients
  ▪ Between patients

Question 2

What factors influence your decision making process of a study design?

Answer 2

✓ Diverse and small population
▪ Increasing power (crossing-over multiple times)
✓ Optimal treatment for individual
✓ Effectiveness at population level
✓ Shortening time lag
▪ Identification → implementation of evidence- based treatment
✓ Heterogeneity
▪ Within patients
▪ Between patients

Question 3

What the types of outcome measures? And how do you incorporate these?

Answer 3

Outcome measure has to be specific to the outcome that was assessed

• patient reported
• proxy report
• biomarker

Types of outcome measures:
1. Hard (diagnoses, morbidity, e.g. myocardial infarction, CVA)
2. Surrogate (easily measurable variable, e.g. laboratory assessments, often not direct measure
of clinical effect)
3. Patient-related (symptoms, quality of life)

• types of outcome measures - what would you like to see
• acceptance and user-friendly
• measurement properties (validity, reliability, responsiveness)

Question 4

What are the steps in patient request for reimbursement?

Answer 4

– unsure –

• prove effect
• cost effectiveness
• approach biggest healthcare provider - smaller ones follow

Question 5

What is deep phenotyping ?

Answer 5

Deep phenotyping:
- the precise + comprehensive analysis of phenotypic abnormalities
- in which the individual components of the phenotype are observed and described

Precision medicine needs precise phenotypes –> use of clinical signs instead of diagnoses - the standard annotation for patients’ phenotypes when describing single gene disorders.

Question 6

What is Goal Attainment Scaling (GAS)? And what is its advantage?

Answer 6

1. What are your goals, defined it
2. Which goal(s) is/are most important to you?
3. Intervention
4. Are your goals achieved?

Advantages/ Disadvantages:
+ sensitive
+ used for heterogeneous population
+ patient involved in treatment

• labor intensive
• complex validation
• unclear for neuropsychiatric goals

eg. ‘I want to walk independently’
-2 –> Adam is not able to stand alone
-1 –> Adam is able to stand up
0 –> Adam is able to take 3 steps
+1 –> Adam is able to walk from bed to bathroom
+2 –> Adam is able to walk from the couch to the kitchen and all the way back

Question 7

Why do we need outcome measures?

Answer 7

• objectively measurable
• valid and reliable
• continuous (even when change in practitioner)
• prevention of over-treatment/under-treatment
• decision-making
• acknowledging treatment