opportunites and challenges in evidence based …

OPPORTUNITES AND CHALLENGES IN EVIDENCE BASED PHARMACY PRACTICE IN CONTEXT TO COVID-19

PANDEMIC AN INTERNATIONAL PERSPECTIVE

DR. SOHIL KHAN

GRIFFITH UNIVERSITY, GOLD COAST, AUSTRALIA

s.khan@griffith.edu.au

Presentation overview

Part 1 Evidence based Pharmacy Practice in COVID-19 era

Part 2 Pharmacists role and opportunities in global health safety

Part 3 The new world

A bird, camel or bat

SARS CoV 1 (2002-04)

H5N1 Bird flu (2002)

H1N1 Swine flu (2009)

MERS (2012)

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All public 1a1he,_n11 con1i11in1 of ten or'more areprohibited.

D. W.Sl[THERLAND,' Mayor,Kelowna, B.C.,

19th ,October, I918

Stages of transmission

STAGE 1 – first appearance of infection (people with travel history); no local spread; very few cases

1 2

STAGE 2 – local transmission; those who were infected spread the virus to close friends or family (every person in contact could be traced and isolated)

3

STAGE 3 – community transmission; infection in public, source of virus cannot be traced; large geographical lockdown

4

STAGE 4 – disease actually becomes an epidemic in a country with widespread infection

Epidemiology and global burden of COVID-19

First case reported in Wuhan, China (1st December 2019)

Pneumonia of unknown origin (31st December 2019)

First case outside China (13th January 2020)

COVID-19 official term (11th February 2020)

Declared pandemic (11th March 2020)

Confirmed cases – over 12M

Deaths

COVID-19 local impact

Infection control

• Hand hygiene, social distancing,

wearing masks, stay at home

Work differently

• Zoom, zoom, zoooom!

Live differently

• No restaurants, cafes, pubs or bars;

take away only; limits on numbers of

people in a room; no playgrounds; no

shopping; stockpile toilet paper?!

COVID-19 global impact

Economic policy

Unemployment

Poverty

Food security

Education

Part 1

EVIDENCE-BASED PHARMACY PRACTICE COVID-19 era

COVID-19 management approach (Prevention)

Social distancing

Hand washing and hygiene

Mask

Cough/sneeze etiquette

Lock down?

Vaccine?

COVID-19 management approach (treatment strategies)

Repurposed drugs

Adjunct therapies

Experimental therapies

Supportive care

• Ventilation

• Anticoagulation

Antivirals – primary treatment ?

Hydroxychloroquine (HCQ) /chloroquine (CQ)

Lopinavir/ritonavir

Remdesivir

Favipiravir

Specific treatment –HCQ Evidence?

Interferes with glycosylation ofACE2

and reduced binding efficiency

Increases pH of lysosomes, makes

cells resistant to viral replications

Reduces transcription of

proinflammatory genes thus reducing

cytokine storm

Specific treatment –HCQ Evidence?

BMJ (Tang et al 2020)

1200 mg loading dose for 3 days f/b 800 mg OD for 2-3 weeks

Outcome – Negative conversion of SARS CoV 2 by 28 days.

JAMA (Rosenberg et al 2020)

High cardiovascular abnormality in HCQ group (baseline

characteristics unequal? Already severe cases, hypoxia)

NEJM (Geleris et al 2020)

Patients on HCQ already with mild/moderate ARDS; several

patients not intubated due to lack of supportive care!

HCQ - the blame game?

Can’t be clearly blamed

Efficacy is still questionable

Cost?

Evidence?

Final nail

HCQ – to be or not to be?

Dose difference – impact on outcome?

ICMR, India recommendation

400 mg BD (day 1) followed by 200 mg BD X 4 days

Total dose 2400 mg

WHO halted study arm

(SOLIDARITY trial)800 mg BD (day 1) followed by 400 mg BD X 4 days

Total dose 9600 mg

Specific treatment– Remdesivir Evidence?

Adenosine analogue; incorporates

into nascent RNA leading to

premature chain termination

200 mg IV (day 1) f/b 100 mg daily

for 5 days

Not recommended in abnormal

liver function test (> 5 times upper

limit of normal)

Remdesivir – to be or not

to be?

“Clearly effective!”

– Fauci

Money – the third axis of choice for remdesivir?

Specific treatment– Corticosteroids Evidence?

Dexamethasone

Efficacy

Severity of COVID-19

• Remdesivir

• Dexamethasone

• Hydroxychloroquine

• Famotidine (H2 receptor antagonist)

Pharmacotherapy in COVID-19 key updates

Supportive care – crucial

Happy hypoxiaOxygen saturation is low

Patient not breathless

Sudden deterioration Respiratory care Anticoagulation

RESEARCH IN TIMES OF PANDEMIC

• Lockdown

• Access to research facilities

• Survey

• Follow-up

MEDICAL INFORMATION EXPLOSION IN

COVID-19 ERA

• More than 30,000 medical papers in the last 4 months

• Doubling every 20 days

• Biggest explosion of scientific literature ever!

• The National Library of Medicine registry ClinicalTrials.gov lists 2800 COVID-19 studies

• Predatory journals/publications!

PRE-PRINTS SERVERS

Postings in MedRxiv have increased over 400% (from 586 for the last 4 months of2019 to 2572 for the first four of 2020),while views and downloads have increased 100-fold

• Preprints may be widely shared and direct practice, but the speed of production may not be matched by critical analysis and the need for replication.

COVID-19

information

explosion

COVID-19 medical literature

“Healthcare practitioners tend to be satisfied with the

information they can readily summon, while often

sacrificing quality for convenience when providing

drug information”

Satisficing

Scott, 2012; Duggan, 2006

Is keeping up to date

Mission Impossible?

Bluegreenblog2006

There is an understandable urgency for evidence-based data synthesis and dissemination during the current crisis and the work being conducted by

practitioners and researchers across the globe is commendable.

The pressure to provide promising data and the race to achieve

recognition, however, should not compromise on quality of

evidence through publication bias and poor study methods.

The ethos of Evidence Based Medicine

• Core principles

• Feasibility, appropriateness,

meaningful, effective

• Core domains

A. Global health and collaboration

B. Evidence generation

C. Evidence synthesis

D. Evidence transfer

E. Evidence implementation

Globalisation in healthcare research

PRINCIPLE (platform randomised trial of interventions against COVID-19 in older people),

RECOVERY (randomised evaluation

of cOViD-19 Therapy) and,

REMap-CAP (a randomised,

embedded, Multi-factorial,

adaptive platform Trial for

community-acquired pneumonia)

Adaptive, agile and based on rigorous scientific principles

Search Smart

Clinical studies: PubMed, EMBASE, CINAHL

Synthesis: Cochrane Database of Systematic

Review, DARE, Joanna Briggs, Clinical Evidence, TRIP

Synopsis: Evidence Based Abstraction Journals

(Medicine, Dentistry, Nursing)

Summaries: Clinical Guidelines, DynaMed,

UptoDate, EvidenceUpdates

Computerised Decision Support: Essential Evidence

Plus, UptoDate

A re research decisions

based on que stions

relevant to users

of research?

Appropriate research

design, methods,

and analysis?

Efficient research

regulation

and manag emen t?

Fu lly accessible research

i nform at ion?

•Low priority questions

addressed

• I mportantoutcomes

not assessed

•More than 50% studies

designedwithout

referenceto systematic

reviewsof existing

evidence

• Adequate steps to

reduce bias not takenin

more than 50% ofstudies

• I nadequat e statistical

power

• I nadequat e replication

of i n it ial fin di ngs

•Compli cit withother

sources of waste

and inefficiency

• Disproport ionateto the

risks of research

•Regu latory and

management processes

are burdensome and

inconsistent

• More than 50% of studies

never fu llyreported

•Biased und er- reporti ng

of stud ies with

disappointing results

•Biased reporti ng of data

wit h i nstudies

Un biased and

usable research reports?

•Morethan 30%of trial

intervent ions not

sufficient lydescribed

• More than 50%of

plannedstudy outcomes

not reported

•Most new research not

interpreted in th e

contextof systematic

assessmen t of other

releva nt evidence

0 0Researchwaste

Figure: Avoidable waste or inefficiency in biomedical research

Part 2

Pharmacists role and opportunities in global health safety

GLOBALIZATIONOFPHARMACY SERVICES

Disease prevention and infection control

Adequate storage and drug supply

Patient care and support for multidisciplinary health team

THE GLOBAL PHARMACIST

• Video-telecon

– Residential Medication Management

Review (RMMR)

– Home medication reviews

• Aged care safety and quality

• Meds Check

• Special care for vulnerable and isolated cohort

• E script

• Vaccination

Part 3

THE NEW WORLD

• We must ensure that we continue to interrogate the uncertainties of COViD-19, review the totality of research to ensure we are notmissing important data, register and report trials, and press for better, not necessarily more, research.

• Pandemics may feel frightening, but even more frightening is

annexing the scientific method in dealing with it.

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Spanish flamenco guitarist Joselito Acedo plays the guitar on his balcony during COVID-19 lockdown in Seville, Spain

Woman wearing a mask sits by a bridge in New York

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Chinatown in Singapore shuts down in the wake of the pandemic

A man wearing a mask goes for a morning jog near the London Eye

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An MTA subway car lies empty during rush hour in New York

People line up outside a convenience store in suburban Mumbai while maintaining the social distance

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People of Auckland have propped upteddy bears in their windows for kids tospot when they are out walking

The deserted shopping hub of Regent Street in the West End, London

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Striking graffiti messages urge locals to stay home, in Fremantle, the port city in Western Australia

The fruit and vegetable delivery with rowing boats in Venice, Italy

The way ahead…

Questions…

s.khan@griffith.edu.au