Transcript Keynote talk in Pune, India by Richard Wormald

Clinical uncertainties in
Glaucoma treatment and
priorities for research
Richard Wormald
Pune December 2015
with gratitude
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Richard Wormald is funded with financial support from the UK's
Department of Health through the award made by the National
Institute for Health Research (NIHR) to Moorfields Eye Hospital
NHS Foundation Trust and UCL Institute of Ophthalmology for a
Specialist Biomedical Research Centre for Ophthalmology.
The views expressed in this presentation are those of the author
and not necessarily those of the Department of Health.
I have no commercial conflicts of interest
I am a board member and trustee for Vision 2020 (UK) and Fred
Hollows UK
I am a grant holder for research from the NIHR
I am joint Co-ordinating Editor of Cochrane Eyes and Vision with
Jennifer Evans, based at the London School of Hygiene &
Medicine's International Centre for Eye Health and Centre for
Evidence and Disability
I am an editorial board member for Ophthalmic Epidemiology,
Journal of Community Eye Health, BioMed Central Ophthalmology
and the Indian Journal of Ophthalmology. I recently stepped down
from Ophthalmology after 12 years
The Cochrane Collaboration
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Cochrane is a global independent network of
health practitioners, researchers, patient
advocates and others, responding to the challenge
of making the vast amounts of evidence generated
through research useful for informing decisions
about health. We are a not-for-profit organisation
with collaborators from over 120 countries working
together to produce credible, accessible health
information that is free from commercial
sponsorship and other conflicts of interest.
The Cochrane Library is published but not owned
by John Wiley on a renewable contract
EVOLUTION
Ho·mo me·di·cus
noun \ˌhō-(ˌ)mō-ˈmē-di-kus/
: eminence-based doctor. Read a paper once and
didn’t like it.
Homo medicus
Ho·mo e·vi·dence
noun \ˌhō-(ˌ)mō-ˈē-vi-dēns/
: evidence-based doctor. Make
research-informed decisions, and
thinks research is useful but
complicated
Homo evidence
Ho·mo sin·the·sys
noun \ˌhō-(ˌ)mo- sin-ˈtē-sis-/
: a mutation of the homo evidence
that sparkled interest in synthesing
research in order to help others.
Homo synthesis
Ho·mo Co·chra·ne
noun \ˌhō-(ˌ)mō-ˈcō-krēn, especially British /
: the species of human that are able to
complete a high quality Cochrane review on time
Models for developing capacity:
inside or out?
Gabriel Rada (@radagabriel)
[email protected]
Evidence-based Health Care Program, Pontificia Universidad Católica de
Chile
Epistemonikos Foundation (@epistemonikos)
Santiago, Chile
What is a clinical uncertainty?
Clinical uncertainties resolved by
systematic reviews and meta-analysis
Or
Uncertainties confirmed and used for
research prioritisation
an example of a clinical
certainty
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an example of a clinical
certainty
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Lens Extraction in Angle
closure glaucoma
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Jen Burr and Augusto Azuara Blanco
Aberdeen Clinical Trials Unit £1.1
million MRC
Network Meta-Analysis of
Glaucoma Medical
Treatment
Trials
Tianjing Li, MD, MHS, PhD
Center for Clinical Trials
Department of Epidemiology, JHBSPH
April 5, 2014
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Network Graph for 114 Trials on First-line Medications for OAG
# of total studies =114
Carteolol
# of participants =20,275
Betaxolol
Levobunolol
Timolol
Brimonidine
Color coding:
Apraclonidine
Levobetaxolol
Grey
Placebo/vehicle/no treatment
Gold
Alpha-2 adrenergic agonist
Green
Beta-blocker
Placebo
Brinzolamide
Red
Carbonic anhydrase inhibitor
Blue
Prostaglandin analog
Unoprostone
Dorzolamide
Tafluprost
Bimatoprost
Latanoprost
Li et al. Ophthalmology 2015
Travoprost
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NMA is often needed to address comparative effectiveness
research questions. Indirect comparisons help to assess the
validity of direct comparisons.
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Based on our analysis, as a single agent, bimatoprost
seems to be the most effective first-line treatment in lowering
IOP at 3 months; as a class, prostaglandins seems to be
best. However, the quality of evidence is low.
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Next steps: analyze other outcomes, including visual fields,
cup/disc ratio, visual acuity, and harms.
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I went through all trials that reported visual field data, which
Kristina and Sueko helped with data abstraction (n=~70).
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There are 6 trials that reported analyzable visual field data
as mean deviation, and 10 trials reported analyzable
improvement or worsening of visual field. However, none of
the these trials were those trials we included in the IOP
analysis.
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Maier et al. BMJ April 06
prevention of progression of glaucoma in
OAG
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The UKGTS, Lancet 2015, now provides the first report
in the literature for a single treatment on VF
outcomes
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UK Glaucoma Treatment Study
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Maier ‘06 + UKGTS
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The Low Tension Glaucoma
treatment study - LoGTS
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Krupin et Al. AJO…
Is Brimonidine neuroprotective
compared to Timolol (standard
treatment) - in low(er) tension
glaucoma
Primary outcome: visual field
progression after 4 years of treatment
The Low Tension Glaucoma
treatment study - LoGTS
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The Low Tension Glaucoma
treatment study - LoGTS
Of the 190 adults enrolled in the study, 12 (6.3%)
were excluded after randomization and 77 (40.5%)
did not complete four years of follow up.
The rate of attrition was unbalanced between
groups with more participants dropping out of the
brimonidine group (55%) than the timolol group
(29%).
High Risk of Bias
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ANSWERS
“…Furthermore, the spatial correlation utilised in
ANSWERS was shown to improve the ability to
detect deterioration, compared to equivalent
models without spatial correlation, especially in
short follow-up series. ANSWERS is a new
efficient method for detecting changes in retinal
function. It allows for better detection of change,
more efficient endpoints and can potentially
shorten the time in clinical trials for new
therapies.”
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CONCLUSION
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Now we are ready to design the
definitive trial for comparing the actual
effectiveness of modern first line
treatments for preventing progression
in glaucoma - in different populations
Prostaglandin analogues, Beta
Blockers and Alpha agonists
Great opportunities for collaborative
multi-centre multinational trials