Patients The Key to Real World Data? Alan G. Wade.
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Transcript of Patients The Key to Real World Data? Alan G. Wade.
Real World Data Sources
29%
41%
18%
6%6%
Sources of Data
Clinical TrialsPatient DataRegistriesPrescribing DataBig Data
Reflects the average patient in a real-world setting• Demographics
– Sex– Age– Social status– Education
• Diagnosis• Co-morbidities• Co-medications• Medical system• Social impact• Work impact• Family impact• Impact on Quality of Life
What is real world data?
Pre market entry disease, burden, unmet need, treatment pathway mapping
Licensing when impact only known by patient or difficult to assess
Labelling extension Validated PRO’s
Market Access HTA; effectiveness
Post license safety, benefit:risk(registry),risk/management plan
Guideline development ???
Uses for “real world” data?
Source
Randomised Controlled TrialsPMS Studies
Physician driven
Patient registriesPrescribing data
Database – physician recorded
Focus groupsPatient organisations
Patients
Traditional data sources
Hierarchies of evidence
1. Systematic reviews of randomised controlled trials (RCTs).
2. RCTs.3. Controlled observational studies - cohort
and case control studies.4. Uncontrolled observational studies - case
reports.5. Expert opinion
?KoL
Randomised Controlled Trials
• “the gold standard” for demonstrating (or refuting) the benefits of a particular intervention.
• Important limitations
Limitations of RCT’s
Patients– Age - Effectiveness in younger or older patients– Sex– Severity - effectiveness in mild or severe– Risk factors - effectiveness in patients with risk factors for the condition (eg, smokers)– Co morbidities - Influence of other conditions– Ethnicity - effectiveness in other ethnic groups– Socioeconomic status - effectiveness in disadvantaged patients
Treatment– Dose - high dose used in RCTs?– Timing of administration Influence on adherence (compliance) to treatment regimens– Duration of therapy - effectiveness during long-term use– Co medication - adverse interactions– Comparative effectiveness - in comparison with other products used for the same indication
Setting– Quality of care – Prescription and monitoring by less specialist (expert) healthcare providers– Care pathway
Effectiveness and efficiency
Does it work in Does it work in Does it contribute to aclinical trials? real life? more efficient use of
resources? COST-EFFECTIVENESS
Efficacy Effectiveness Efficiency
To assess performance of drug in real world setting– Large numbers– Off-label prescribing– Comorbidities– Concomitant medications– Speed of reporting
Do we achieve this with formal PMS?
Post Marketing Surveillance
Hierarchies of evidence
1. Systematic reviews of randomised controlled trials (RCTs).
2. RCTs.3. Controlled observational studies - cohort
and case control studies.4. Uncontrolled observational studies - case
reports.5. Expert opinion
?KoL
6. Patient reports ?
Harveian Oration
Hierarchies of evidence should be replaced by accepting—
indeed embracing—a diversity of approaches.
The Lancet Vol 372 December 20/27, 2008
NICE
Patient and public involvement
The views of patients, carers and the public matter to NICE. We want to involve them, as well as doctors, nurses, other healthcare professionals and managers in our work.
http://www.nice.org.uk – accessed 22 06 09
EMA
The assessment of the benefit-risk balance should be based on the available tests and trials, which are designed to determine the efficacy and safety of the product under normal conditions of use (Directive 2001/83), and which are generally performed under ideal conditions.It is important to be explicit about the perspectives of different stakeholders that are taken into account in the assessment of the benefit-risk balance, in particular the perspectives of patients and treating physicians.Considerations about how the treatment is expected to perform under real conditions of use are relevant in the context of pharmacovigilance activities, for example, to take into account any available information on misuse and abuse of medicinal products which may have an impact on the evaluationof their benefits and risks (Directive 2001/83).
Patient groups - the patient?
EPF is the umbrella organisation of pan-European patient organisations active in the field of European public
health and health advocacy.
The European Patients’ Forum (EPF) currently represents 57 patient
organisations and an estimated 150 million patients across the 27 Member
States throughout Europe.
EU drugs agency working with patient groups bankrolled by big pharma
23.04.10 @ 19:17
Patient organisations
But equally, we have a right and responsibility to look at the interests of other patients who use the healthcare system. What I am critical of, however, is patient organisations that are acting on behalf of pharma companies. I am not alone in complaining about them.
The Lancet Vol 372 December 20/27, 2008
Harveian Oration
No single agreed definition
but
The bottom line: whatever the disagreements over the definition, everybody agrees on one thing: big data is a big deal, and will lead to huge new opportunities in the coming years.
Big Data - definition
http://timoelliott.com/blog/2013/07/7-definitions-of-big-data-you-should-know-about.html Accessed 27 01 14
Big Data – Pharma???
22
RegistriesClaims Databases (US)
e - Medical Records
Also
Pharmacy databasesSpecific hospital databasesSpecific disease or procedure databases
What do you want from a registry?
• Large numbers• Patient level data• Immediacy of data• Longitudinal data• Representative population
• Presence of YOUR required data• Linkage of data fields of interest• Confirmation of diagnosis• Standardised measurement• Validated PRO’s
Existing registries
Strengths• Large numbers• Immediate access• Longitudinal data
• Prescribing data
Weaknesses• Inherent biases• Representative population• Diagnostic drift • Patient level data• Surrogate outcomes• Completeness of data• Family social and work history
To effectively use any registry it is important to understand how it has been developed and its strengths and weaknesses
• Some treatment effects only known to patient• Pts provide unique perspective on treatment• Provide information on QoL, work, social and
family
• Formal assessment may be more reliable than informal interview
Patient Reported Outcomes Why & How?
25
What the Patient Knows
What the Patient Shares
What the physician understands
What the Physician records
Big Data
Addressing registry weaknesses
Ask the patient – but how?
Real World Data Sources
29%
41%
18%
6%6%
Sources of Data
Clinical TrialsPatient DataRegistriesPrescribing DataBig Data
• “any aspect of patients health status that comes directly from patient” - FDA
• “insight into way patients perceive their health & impact treatments or adjustments to lifestyle have on their quality of life” –DH
Patient Reported Outcomes - Definition
29
• Pt recording versus doctor• Pt understanding of question/form• Validity of question (in that format, pt popn)• Reliability of question• Ability of question to detect change• For licensing – need set as per RCT
Patient Reported Outcomes – concerns
31
Definition of “Real Data from Real Patients”
• Collecting data from patients receiving “routine care”
BUT• Not affecting their prescribers/ healthcare
professionals behaviour
Process set-up
• Define question - protocol• Define patient group of interest• Determine location of group e.g. Specialist unit,
community setting, geography• Review options for accessing patient group
– Orphan indications
• Design questionnaires and reports– development and testing
• Structure customised database
• Bespoke – ask required questions• Innovative• Prospective• Hosted on Patients Direct site• Interactive• Global Coverage
Structured patient registries
35
• Is on-line collection satisfactory?• Will patients cooperate• How do you recruit?
– Methodology– Achieving a representative population
Problems
• Outlet for their feelings and views – might be a threat to their relationship if they report problems to their healthcare professional – we’re neutral
• Altruistic - Assist in developing new and better treatments
• Obtain better information and knowledge through participation• Feel valued through regular contact/ interaction• Desire to make sure the patients voice is heard
Why do people participate?
42
...the benefits and attraction to each individual will differ but we believe the main reasons are :
7. REPORT CONCLUSIONS.
The above report has shown the public’s enthusiasm towards a system that would let
consumers report adverse drug reactions through the Internet. The findings of the
survey carried out by us revealed to us this enthusiasm. The report has further shown
that health professionals have a positive opinion towards such a system, which
works
in favour of the overall mission of Patients Direct. Not only has the report articulated
the publicity campaign that Patients Direct can carry out to raise its awareness, but
also examples of different medicine inserts has been provided with reasoning behind
them that could be used by the company to make itself different from its competition.
Patients Directs corporate identity is important to begin the process of publicity. IT
has been noted that establishing a user friendly website that is easily navigable is
fundamental to setting the pace for a strong brand and image that will appeal to
Patient’s Direct customers.
Will patients cooperate?
43EDGE Survey - Market Research, 2008
• social networking sites• search engine and website optimisation • public affairs articles and traditional methods of publicity e.g.
Newsprint/TV• Healthcare professionals –Doctors, pharmacists• wholesalers, distributors• Clinical trial participants• patient groups Special focus can be given to groups of interest such as children if
appropriate and recruitment monitored to ensure sufficient numbers in each cohort.
Recruitment
...tailored to attract patients of interest with a conscious effort to reduce bias and population selection issues
Core recruitment methods include :
Recruitment Examples
• General – statins– Pharmacy/wholesale distributor– Advertising - Google
• Vaccines– Direct at vaccination
• Families and children– Appropriate web-sites
• Specialist product – home delivery– Invitation with delivery
• OTC – Strepsils– General advertising– Pharmacy– Package wrap
52
Respondents
Started Completed Incomplete Meets IBP Criteria
0
50
100
150
200
250
300 262
151
10879
53
Age Profile
Under 30
31 to 40 41 to 50 51 to 60 61 to 70 Over 700
1020304050607080
5257
77
36
15
2
56
Age Profile of Respondents with IBP
Under 30
31 to 40 41 to 50 51 to 60 61 to 70 Over 700
5
10
15
20
25
30
35
16
24
32
13
41
Influenza Family Study
Family Influenza Survey
Households completed study 946
Individuals in completer households 3695
Flu-like Illness episodes in households
540
Total “Flu-like” Illness 851
Considerations
• Data Protection/ Confidentiality• Ethics
– NRES response
• Industry Code of Practice• Safety Reporting systems – MHRA
– Automated A/E reporting– A/E cascade
• Medical considerations/standards– No interference with prescribing/treatment
Process - management
• Patient response handling and back up• Review of data as study progresses• Design of reports
– A/E reporting in agreement with sponsors
• Statistical interpretation and reporting• Publications• If appropriate, patient education or further action
e.g. Adherence schemes
Managing data – a dynamic processReal data from Real patients
61
Patient
www......./ tel
Database
“continuous” Output
Analysis and report
Retrospective Prospectivepatient
Presence of YOUR required data + +++
Representative population + ++
Large numbers +++ ++
Linkage of data fields of interest ? +++
Confirmation of diagnosis ++ ++
Standardised measurement + +++
Validated PRO’s + ++
Patient level data + +++
Unfiltered patient data - +++
Response to unexpected findings + +++
Immediacy of data +++ ++
Longitudinal data - Retro/pro ..... spective +++ +++
Sensitivity + ++
Registries
• Medical interventions are now being assessed on the basis of “real world” data
• Current collection methods are inadequate• Novel systems for collection are required• Patients are increasingly being involved in
medical decision making• Collecting “real world” data directly from patients
may be one possible method
Summary
Mapping Treatment Pathways
Burden of Illness
Drug Safety/ PV
Real world “effectiveness”benefit QOL
Patient Satisfaction/experience/Adherence
CVA evaluation
Sleep evaluation
Wellbeing Study (depression)
Problem Periods survey
Problem Periods survey
Impact of opioid use
CVA evaluation
Family Flu survey
Statin survey
Swine vs seasonal flu vaccination
Seasonal flu vaccination 2008
EQ 5D mapping 3 level to 5 level
Etanercept survey
Satisfaction with analgesia in OA
Pulse Rate survey
Etanercept survey
Satisfaction with analgesia in OA
Project examples
66
PV - Flu Vaccination
• 102 leaflets distributed• 73 PIN numbers have been entered on the database (72%)• 40 male and 33 female aged between 21 and 99 years. • They were asked about pain and discomfort from the vaccination
67
Flu Vaccination - Day 2• 70 responses were entered for Day 2• 14 having side-effects.
02468
1012
NothingTreated it yourself
012345678
rednessdiarrhoealoss of appetiteother
68
In response to “What did you doabout these side effects?”
Reported Side Effects
HiVE - H1N1 Vaccination Evaluation
H1N1 only seasonal only both +travel/pnemococcal0
100
200
300
400
500
600
700
800
Vaccination Received
Co
un
t
HiVE - Demographics
< 5 5-29 30-49 50-69 70 +0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
Age of Participants
Male – 449Female - 663
HiVE - Adherence
Baseline Week 6 Week 12 Week 260
200
400
600
800
1000
12001112
716646
570
Number of Participants
HiVE – Side effects
Baseline week 6 week 12 week 260
5
10
15
20
25
30
35
40
45
50
Any Side Effects over time
Swine only
Seasonal only
Both
%
Injection site discomfort
36.4%
Flu-like symptoms
23.5%
Injection site pain
20.1%
χ2-test p <0.001
H1N1 only
HiVE - Absenteeism
Baseline Week 6 Week 12 Week 260
1
2
3
4
5
6
Time of Work due to flu like symptoms
H1N1 only
Seasonal Only
Both
% w
ith
tim
e o
ff
HiVE – Pain/Discomfort Reports
Category Odds ratio P valueSex Male
female 2.08 0.052
Chr illness NoYes 1.32 0.052
Swine flu vaccine NoYes 4.49 <0.001
Seasonal flu vaccine NoYes 0.89 0.481
Subject participates
“Buy-in”
Enrols “Buddy”
Feedback on outcome
Engaged for next year
“Viral Transmission”
Subject + Buddies + “Virals”
The Virtuous
Cycle
• Delivery at home• Compliance with drug still low• Understand agency effectiveness, reasons for
drop outs• Understand real life prescribing vs guidelines• Evaluate and then implement ways of improving
outcomes• Measures – AEs, compliance, QOL – disease
specific and generic EQ5D
Enbrel Project
76
Enbrel - Process
77
• Patient group recruited through leaflets with hospital clinic or HaH nurse visit to train on injection
• Initially 6 month follow up at 1 month intervals
• Recently extended to 2 year follow up at 3 month intervals
• Enrolled 344 patients • Out of ~1000 leaflets distributed• 284 patients by web site• 60 patients by telephone
• 93-100% completion of questions at baseline
• 140 patients have reached month 6
Enbrel – First 6 months
78
If you are experiencing problems with the website or any of the questions please contact the following number and we will endeavour te help you: 0800 731 2647
Age of Participants
< 10 10-19 20-39 40-59 60 + missing0
20
40
60
80
100
120
140
160
180
AllRA only
Nu
mb
er e
nro
lled
Baseline Use of Methotrexate
All RA AS PsArth0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
noyesnot sure
• Examples – MS, epilepsy, gout, infectious illness, depression
• Pre programmed questionnaire – timing ??• Baseline then every month/ 2 weeks -
recall?• Simple email – yes or no• Rely on people saying when they have
“event”
Intermittent events- data gathering
82
• Capture QoL changes when worst time of cycle
• Variation within and between women
• Compare to “normal” time
Intermittent Condition – Problem Periods
83
2699 respondents
Age – good range from < 20 to > 49 (61% < 30)
Absenteeism – 3+ days/mth 6%
1-2 days/mth 16%
Results – Screening survey
84
Significant impact on ALL Quality of Life Scales
Significant change between the different times of period cycle
Results – Main Outcomes
85
Main outcomes – EQ5D
86
Day 1 Day 2 Day 3 Day 4 Day 5 Day 60
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8EQ5D Score
Mean
• Routinely gather PRO on• All Medication related to condition• Doctor visits (Primary & Secondary care)• Nurse visits• Pharmacy visits• Telephone calls (if relevant)• Hospital In/ Out Patient visits and number of
days
Resource utilisation
88
A real world study using Patient Reported Outcomes to assess the consequences associated with the forced switching of asthma
medication/device in stable adult asthma patients
• Data to be captured from Patients themselves:
• baseline patient reported level of Asthma control/satisfaction with device
• Reasons for switch (if known) (prospectively)• Outcomes of switch: Clinical (FEV1, Control)
Health resource use (GP visits, hospitalisations) lifestyle impact (days off work) (prospective)
• The questionnaires would be administered monthly (prospectively) so that any changes are captured 89
• Unmet need• Gathering information on children/ adolescents/
parents• Adherence, satisfaction, burden of illness
Cystic Fibrosis
90
• If you need real world PRO data in Europe/US• Databases don’t collect info you need
• Patients Direct can collect the data, directly from the patient
Quick, efficient, cost effective solution
Conclusion
91
• Burden Of Illness Study – Depression Management
• Understanding Patients ability to monitor their own condition – Heart Rate survey
• Disease treatment pathway mapping – CVA Study
• Mapping new EQ5D• Are QALYs appropriate across EU ?
Market Access
92
• Socio-demographics,• PMHx, • Resources use – Client Service Receipt Inventory
• QOL - EuroQoL• Productivity – WHO Health & Productivity Questionnaire
• Depression – HAM-D, MADRS
Burden Of Illness - 300 pts depression
93
• Medical pathway of ischaemic stroke until 1 year acute episode
• Cost of stroke management• Cost drivers• Comparison between UK, France, Germany
Disease Pathway and Management
96
• Socio-demographic• Pre hospital management – PMHx, 1st contact,
transport• Hospital management – treatments,
investigations• Post hospital management - rehabilitation
Disease Pathway and Management
97
• New 5 level questionnaire (from 3 level)
• 500 pts UK
• Different levels disability
• CV disease, Respiratory, Neurological, RA
EQ 5D Mapping
98
• FP 7 grant• Pan European – UK arm (with A Walker)• University of Lyon
• Identification of different methods in HTA• Review of different methods• Alternatives to QALY
Use of QALY across EU
99
• Involved in questionnaire mapping• Gathered data via various QoL scales• Gathered data on inputs and outputs -
costs, diseases, outcome• Individuals involved in SMC and NICE
submissions and Advisory Boards• Access and use of UK experts –
Robertson Centre
HE and OR
100
• Bespoke Innovative solutions• Professional Quality Assurance /control• History of delivering results
– On time– Value for Money
• Tailored to sponsor brief• Multiple Applications
Summary
101