use of real-world data in radiotherapy

1. Use of real-world data to
provide evidence in the field of
radiotherapy
Dr Pallavi Kalbande
Clinical Oncologist
India

2. Real world evidence
• Generated from real world data
• from medical practice among heterogeneous sets of patients in real-
life settings
• Insurance claims data
• Clinical data from electronic health records

3. • Randomized clinical trials (RCTs) are the
gold standard for rational therapeutics
Evidence based Medicine

4. Limitations of RCT
• Highly expensive
• Resource - intense
• Not feasibility for every indication
• Inherent selection bias
• less diverse than their real-world
• Time consuming

5. Annual Incidence

6. Fact about clinical trials
• <5% of adult cancer patients enroll in clinical trials
• Enrollment in cancer trials is low for all patient groups
https://doi.org/10.1001/jama.291.22.2720
192 millions
52 millions
49 millions (95%)
2 millions (5%)
Clinical Trial

7. Pub Med citations with “real-world evidence”
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8. Expedite drug approvals
• The US FDA has provided three-phase clinical trial approach to
expedite drug approvals in cancer
• It has halved the drug development time
• Large number of chemotherapy, targeted therapy, immunotherapy
drugs are coming in the market
• Radiotherapy can't go with this because of worrisome long term side
effects
• Radiotherapy is lagging behind

9. Uses of RWD in Radiotherapy
• Expanding on safety of a Radiotherapy
• Studying various populations
• Comparing RWE end points with those of RCTs
• Potentially expanding on indications
• Validating observed efficacy in RCT results
• Cost of care, resource use, and even
• Efficacy and toxicity in a non-RCT population for established indications

10. Advantages
• Provides important insights into patterns of
care
• Current unmet needs
• Help understand a potential role in the
therapeutic approach
• Facilitate clinical trial design and acceleration of
novel therapies by characterizing patient
populations in need
• health care use costs
• Discovery of toxicities otherwise Promotes
culture of data sharing Facilitates post
marketing surveillance
• Can encourage drug-repurposing efforts
• Cannot definitively answer the
superiority of RT
• Approve a new treatment
indication
• Alternatives to RCTs can provide
misleading conclusions
• Justification of interventions that
alter current standards of care
limitations

11. Cautions!!
• Contradictory results are neither unique
• Ground upon which RWE stands is less firm
• Results should most often be considered with
that understanding
• Results must be interpreted in context, with a
complete understanding of the methodologic
limitations

12. Delicate balance
• Between the need
for RCTs and where
RWE could fulfill a
scientific gap

14. • Contradictory results are neither unique to observational studies or
RWE nor to RCTs, but the ground upon which RWE stands is less firm,
and results should most often be considered with that understanding
• We make the point that RWE research, albeit highly valuable, must be
interpreted in context, with a complete understanding of the
methodologic limitations. Indeed, some helpful advice in preventing
researchers and readers from making misleading conclusions based
on observational data have recently been published.19

15. • RWE and observational studies are a reasonable consideration for a
health care intervention when the following criteria are all fulfilled:
high health care use, no or equivalent risk of harm as seen in a
healthy population, and no added cos
• , it is not always necessary to be precise and definitive when
investigating a benign intervention

16. • Although RCTs are essential to study the validity of precision
oncology, RWE could supplement any findings by validating the
results and applicability to larger numbers of patients treated in the
real world.
• ideal situation is a harmonized partnership between RWE and RCTs,
especially when RWE complements the findings from RCTs, such as
uncovering long-term safety signals and establishing efficacy in
populations under-represented in RCTs.

17. Advantages of RWE
• RWE cannot replace RCTs in this setting, because there are risks of harm when
patients receive ineffective or potentially toxic
• Toxicity Helps uncover important toxicity signals that require long follow-up
• Not suitable for approving interventions but helpful to validate RCT findings
• Can reveal some important target-drug combinations for later testing in an RCT
Helpful to definitively test the target-drug combinations identified through RWE
Can encourage drug-repurposing efforts in precision oncology25 PragmaticRCTs
can act as a middleway betweenRWE and RCT in precision oncology

19. • Promotes culture of data sharing Facilitates postmarketing surveillance
• as we increase the use of RWE, we believe it is critical that its research
tools be used appropriately to complement RCTs where highly selected
patientswere enrolled andwhere precision biomarker data that are difficult
to obtainin the real world might have been applied.
• Where applicable, RWE can expand on current knowledge and drive the
design of subsequent clinical trials on the basis of findings from
observational studies

20. • We propose simple criteria for consideration where RWE can
potentially replace highly expensive and resourceintense RCTs;
however, it cannot yet do so for precision oncology. This proper
balance between RCTs and RWE will become increasingly critical as
we move further into the era of precision medicine

21. • is that for interventions with risk of harm, alternatives to RCTs can
provide misleading conclusions. How observational studies and RWE
complement RCTs in an era of precision medicine and valuebased
care may be a million-dollar question.

22. Application of real-world evidence
• Highlight diseases not currently served by existing treatments and
current unmet needs • Help understand a potential role in the
therapeutic approach • Facilitate clinical trial design and acceleration
of novel therapies by characterizing patient populations in need
• Estimate treatment effect • Allow comparisons between real-world
treatment effectiveness and efficacy from clinical trial data •
Contribute to knowledge of patient safety • Inform clinical trial design
and appropriate end point usage • Describe patient populations (e.g.,
characterize patients in underpowered subgroup analyses) • Act as
external control for single-arm clinical trials

23. • Expedited approvals have nearly halved the historical pace of bench-
to-bedside drug development from 12 to 6 years.
• Whether new therapies come to market through an expedited or
traditional approval process, evidencebased medicine requires robust
safety and efficacy data to assure optimal patient outcomes. The
resources required to attain these results are inadequate given the
demands on ourhealthcare system

24. • A white paper authored by various stakeholders highlighted five
potential uses for RWE: expanding on safety of a therapeutic,
studying various populations, comparing RWE end points with those
of RCTs, potentially expanding onindications, and validating observed
efficacy in RCT results.
• However, RWE cannot definitively answer whether an intervention is
superior to a control, a question that assumes prime importance in
deciding whether to approve a new treatment indication. Thus, the
utility of RWE may be limited when clinical trial rigor is vital to avoid
harm or a definitive answer is needed.

25. • is that for interventions with risk of harm, alternatives to RCTs can
provide misleading conclusions. How observational studies and RWE
complement RCTs in an era of precision medicine and valuebased
care may be a million-dollar question.

26. • These studies demonstrate the delicate balance between the need for
RCTs and where RWE could fulfill a scientific gap.

27. • Although in our opinion RWE may be of limited value in new
indications of radiotherapy approvals or justification of interventions
that alter current standards of care, it remains valuable in
understanding patterns of care, cost of care, resource use, and even
efficacy and toxicity in a non-RCT population for established
interventions.