Analyzing Clinical Trial Results for Rare Diseases: Challenges, Highlights & Missing Data
A
nalysis of an article presenting
clinical trial results
Dan O’Connor: doconnor@abpi.org.uk
March 2024
V
iews expressed are mine and do not necessarily constitute ABPI policy
A
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What are the challenges of
clinical trials for rare diseases
highlighted in the article?
•
What were the good points
of the study conducted in the
article? What were the
weaknesses?
•
What data is included and
what is not/what is missing
that would have been
interesting to know?
H
o
w
t
o
g
e
t
w
a
r
m
e
d
u
p
1.
H
ow do you find an article that you might be interested in?
2.
H
ow are you reassured it is robust and of high quality?
3.
W
hat is the journal impact factor? Does it matter?
4.
What makes a good T
itle?
5.
W
ho are the authors?
6.
A
bstract should tell you whether to go deeper
W
hy shouldn’t you rely on it for your conclusions?
N
e
x
t
s
t
e
p
s
-
i
n
t
r
o
d
u
c
t
i
o
n
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Introduction should provide relevant information on the
condition and research setting – also provides key
background information
•
What important information does it tell you about the
surrogate marker? (
clinical trial endpoint used as a substitute
for a direct measure of how a patient feels, functions, or
survives
)
•
Scientific rationale for why this study should take place
•
Provides background on an inconclusive study
•
Need to carefully review all evidence – build the next stage
such as dosing requirement - often missing in repurposing
N
e
x
t
s
t
e
p
s
–
m
e
t
h
o
d
s
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Methods – essential to read
•
Why randomise? Why blind if you can?
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Acceptability of no treatment control
•
Study sites – France, UK and Slovakia (+Jordan)
•
Primary endpoint is a biochemical surrogate endpoint -
relevance to patients?
•
Age - over 25 years
•
Challenges in recruitment 19 patients from Jordan
•
Statistical analysis – normally need expert input
N
e
x
t
s
t
e
p
s
-
r
e
s
u
l
t
s
•
Participant flow – tells the story of the trial recruitment and
retention
N
e
x
t
s
t
e
p
s
-
r
e
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u
l
t
s
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Base characteristics – tells you who was in the study – is it
representative?
N
e
x
t
s
t
e
p
s
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r
e
s
u
l
t
s
•
Looks impressive?
•
Look at the scales
•
Statistically significant
versus surrogate versus
clinically relevant?
•
Watch out for subgroup
analysis and over
interpretation
N
e
x
t
s
t
e
p
s
-
r
e
s
u
l
t
s
•
Don’t forget safety and
tolerability
•
Studies nearly always
powered for efficacy
•
Safety signals problematic
in small populations
•
Study drug related events
•
Discontinuations?
N
e
x
t
s
t
e
p
s
–
D
i
s
c
u
s
s
i
o
n
s
e
t
c
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Discussion should be balanced and critical – not always
•
Lancet has Research in Context – very useful
•
Don’t forget to look at the declaration of interest – why?
•
References can be helpful for your next read!
R
e
f
e
r
e
n
c
e
s
•
Highly recommend: How to Read a Paper:
The Basics of Evidence-based Medicine
and Healthcare, Trisha Greenhalgh
•
ICH guidelines -
ICH Official web site : ICH
– efficacy guidelines
concerned with the
design, conduct, safety and reporting of
clinical trials
•
Finding paper – pubmed search engine -
PubMed (nih.gov)
Q
&
A
This analysis delves into the challenges, strengths, weaknesses, and missing data in a clinical trial study focusing on rare diseases. It critiques aspects such as recruitment, study design, surrogate markers, and statistical analysis, offering valuable insights for interpreting clinical trial results effectively.
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Presentation Transcript
Analysis of an article presenting clinical trial results Dan O Connor: doconnor@abpi.org.uk March 2024 Views expressed are mine and do not necessarily constitute ABPI policy
Article analysis What are the challenges of clinical trials for rare diseases highlighted in the article? What were the good points of the study conducted in the article? What were the weaknesses? What data is included and what is not/what is missing that would have been interesting to know?
How to get warmed up 1. How do you find an article that you might be interested in? 2. How are you reassured it is robust and of high quality? 3. What is the journal impact factor? Does it matter? 4. What makes a good Title? 5. Who are the authors? 6. Abstract should tell you whether to go deeper Why shouldn t you rely on it for your conclusions?
Next steps - introduction Introduction should provide relevant information on the condition and research setting also provides key background information What important information does it tell you about the surrogate marker? (clinical trial endpoint used as a substitute for a direct measure of how a patient feels, functions, or survives) Scientific rationale for why this study should take place Provides background on an inconclusive study Need to carefully review all evidence build the next stage such as dosing requirement - often missing in repurposing
Next steps methods Methods essential to read Why randomise? Why blind if you can? Acceptability of no treatment control Study sites France, UK and Slovakia (+Jordan) Primary endpoint is a biochemical surrogate endpoint - relevance to patients? Age - over 25 years Challenges in recruitment 19 patients from Jordan Statistical analysis normally need expert input
Next steps - results Participant flow tells the story of the trial recruitment and retention
Next steps - results Base characteristics tells you who was in the study is it representative?
Next steps - results Looks impressive? Look at the scales Statistically significant versus surrogate versus clinically relevant? Watch out for subgroup analysis and over interpretation
Next steps - results Don t forget safety and tolerability Studies nearly always powered for efficacy Safety signals problematic in small populations Study drug related events Discontinuations?
Next steps Discussions etc Discussion should be balanced and critical not always Lancet has Research in Context very useful Don t forget to look at the declaration of interest why? References can be helpful for your next read!
References Highly recommend: How to Read a Paper: The Basics of Evidence-based Medicine and Healthcare, Trisha Greenhalgh ICH guidelines - ICH Official web site : ICH efficacy guidelines concerned with the design, conduct, safety and reporting of clinical trials Finding paper pubmed search engine - PubMed (nih.gov)
