11/6/2021

Introduction to

Real-World Data and

Real-World Evidence

Erna Kristin
Faculty of Medicine, Public Health and Nursing UGM,
Yogyakarta, Indonesia

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Kategori Registrasi & Penilaian

Obat

Obat Obat Produk

baru Copy biologi

Bentuk Vaksin,
Zat aktif Indikasi sediaan/rute Zat aktif = imunosera,
yang sudah
baru baru pemberian
terdaftar
produk
baru darah

Expanded access
• Sometimes called “compassionate use”, expanded access is a potential pathway for a patient with an
immediately life-threatening condition or serious disease or condition to gain access to an investigational
medical product (drug, biologic, or medical device) for treatment outside of clinical trials when no
comparable or satisfactory alternative therapy options are available.

Accelerated Approval Program

• to allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need
based on a surrogate endpoint. ... The use of a surrogate endpoint can considerably shorten the time
required prior to receiving FDA approval.

Emergency Use Authorizations

• allows FDA to help strengthen the nation’s public health protections against chemical, biological,
radiological, and nuclear (CBRN) threats including infectious diseases, by facilitating the availability and
use of medical countermeasures (MCMs) needed during public health emergencies.

The Regulatory Reliance

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The Cone of Evidence development is changing

Variances in populations utilizing

technology vs the populations
studied

Differing age groups (elderly,

pediatrics)
Race, ethnicity & gender
variances

Population Studied Unstudied co-morbid conditions

Differing concomitant drugs

(including OTC)
Lifestyle variances including
smoking, dietary habits

Differences in disease severity

Varying levels of compliance

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Is there an efficacy-effectiveness gap?

The observed discrepancy between effects of a health intervention in

routine clinical practice as compared with the effects demonstrated in
randomised controlled clinical trials. (Adapted from Eichler et al.,
2011)

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WHO INT

Large clinical trials are an important way to show if vaccines are safe and effective. An
effective vaccine reduces mild, moderate and severe cases of COVID-19.

After you’re vaccinated, it’s possible to spread the infection to others without getting the
disease yourself. Continue to wear a mask, clean your hands, and keep a safe distance.

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Why is this an issue?

Results from
RCT’s used to:
• Extrapolate long-term
safety and efficacy
• Model effectiveness
• Assess and decide on
relative effectiveness

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Why is this happening now?

The use of computers, mobile devices, wearables and
other biosensors to gather and store huge amounts of
health-related data has been rapidly accelerating.

This data holds potential to allow us to better design and

conduct clinical trials and studies in the health care
setting to answer questions previously though infeasible.

In addition, with the development of sophisticated, new

analytical capabilities, we are better able to analyze
these data and apply the results of our analyses to
medical product development and approval.

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What are RWD and where do they come from?

Real-world data are the data relating to patient health

status and/or the delivery of health care routinely
collected from a variety of sources. RWD can come
from a number of sources, for example:

• Electronic health records (EHRs)

• Claims and billing activities
• Product and disease registries
• Patient-generated data including in home-use settings
• Data gathered from other sources that can inform on health
status, such as mobile devices

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Opportunities of Real World Data

Development Authorisation Post - authorisation

Validation of surrogate endpoints

Characterisation of natural history of the disease and unmet need

Identification of the target population

Understanding current clinical care practices (resource utilisation)

Use of historical controls (rare / orphan diseases)

Drug utilisation

Understanding potential knowledge gaps

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ASPIRIN

Despite the absence of control groups, Craven's studies had their basis
in sound reasoning and in the observation of large numbers of patients.

1950 he published his 1st letter in the Annals of Western Medicine and
Surgery, in which he introduced his hypothesis that aspirin was
preventive of coronary thrombosis.

Aspirin prolonged prothrombin time

In 1953, Dr. Craven published his 3rd paper,20 in the Mississippi Valley Medical
Journal. By this time, he had changed his age recommendations for daily aspirin
prescription. He now prescribed daily aspirin to men between the ages of 45 and 65
who were overweight and led sedentary lifestyles, factors that predispose a patient
to myocardial infarction.

Ironically, on 18 August 1957, Lawrence Craven died after experiencing

a myocardial infarction. At the time of his death, he was 74 years old
and still actively practicing medicine

It is noteworthy, however, that Craven's recommendations are not far

from today's widely accepted standards
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1954 Salk polio vaccine trials

Biggest public health experiment ever

Polio epidemics hit U.S. in 20th century

Struck hardest at children

Responsible for 6% of deaths among 5- to 9- year-olds

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The ultimate experiment involved over 1.6 million children, with over 600,000 children inoculated

Results of vaccine trials

The randomized, controlled experiment

Size Rate (per 100,000)
Treatment 200,000 28

Control 200,000 71

No consent 350,000 46

The Observed Control study

Size Rate (per 100,000)

Grade 2 (vaccine) 225,000 25
Grade 1, 3 (control) 725,000 54
Grade 2 (no consent) 125,000 44

Source: Thomas Francis, J r., “An evaluation of the 1954 Poliomyelitis vaccine
trials---summary report,” American Journal of Public Health vol 45 (1955) pp. 1-63.
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FDA revised 7/29/2021

INDICATIONS

Prophylaxis Of Organ Rejection In Kidney, Liver, And Heart Transplant

PROGRAF® is indicated for the prophylaxis of organ rejection, in adult and pediatric patients receiving allogeneic kidney
transplant, liver transplants [see Clinical Studies] and heart transplant, in combination with other immunosuppressants.

Obat di Fornas 2021

a) Untuk pasien pascatransplantasi hati atau ginjal yang telah mendapat imunosupresan lainnya,
tetapi tidak respons.

b) Untuk pencegahan rejeksi pada transplantasi hati atau ginjal.

July 16, 2021

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Hierarchy of Research Evidence

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Research Approach Elaboration

Strength of
Research approaches Time Cost
evidence
Randomized Controlled Trial Years Tens of High
Million $
Pragmatic Trial
Prospective observational cohort
study & patient registry

Hybrid design
Distributed data network
Chart review
EMR data analysis
Claims Data analysis Months Tens to Low
hundreds of
thousands $
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RCT vs. Real World Evidence

Traditional RCT Model RWE Model

Safety, clinical efficacy Effectiveness in the real world

Real world setting (busy practices,

Ideal, controlled setting
patients who are not prescreened)
Several thousand patients over relatively Up to millions of patients over longer
short period of time durations

Generalizable study findings

Randomization remains most effective
tool for reducing bias and confounding
Facts about patient journeys and
outcomes
Low recruitment or high dropout can Comprehensive clinical effectiveness
affect sample size/statistical power evidence

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Faster patient access to innovation24
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Different Perspectives & Needs

Patient
Provider
Payer
Regulator
Pharma

Evaluate efficacy Identify & detect Cost Local relevant Which treat-
to improve safety signals effectiveness evidence ment is safer
patient outcomes & affordable
Explore new Ensure long-term Determine value Ensure reim- Benefit vs risk
indications effectiveness & coverage bursement

Prove value Utilization Improve care Quality of life

review
Publication Publication

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Later phase RWE research can inform future early phase research and
decision making

ISPE &
ISPOR

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Conclusion

In the real
setting, only
RCT has it’s several part of
own objective, evidence FDA framework will include consideration of the
reliable, and worked following:
valid evidence appropriately,
others may
not

2. Whether the
trial or study
design used to
generate RWE 3. Whether the
1. Whether the can provide study conduct
RWD are fit for adequate scientific meets FDA
use evidence to regulatory
answer or help requirements
answer
theregulatory
question

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