opt-in, opt-out, & patient led databases · 7 n es ng 5,000 e-esearch clinical trials sale al...
TRANSCRIPT
Duane Schulthess
Managing Director
Copyright Vital Transformation - CONFIDENTIAL
Opt-in, Opt-out,
& Patient Led Databases Better Patient Outcomes,
Faster and Cheaper
Researchers are:
Dr. Daniel Gassull Duane Schulthess
2 © Copyright Vital Transformation - 2014
12/11/2014 3 © Copyright Vital Transformation - 2014
Sponsors and Supporters of the project:
Assumptions & Limitations:
• The theoretical time impact of databases on identification and
sign-in has been discussed and presented to numerous clinical
trial managers and researchers; these times are theoretical as
well as untested, and should be seen as goals or targets
• We assume the use of patient databases in Europe is
unaffected by the data protection legislation passed in the
European Parliament in March of 2014
• The ROI & Cost assumptions are based on averages across
therapeutic areas; our model is illustrative of relative, not
specific, value
• We assume there are many searchable health databases
operational in numerous international locations, this may not
be the case
4 © Copyright Vital Transformation - 2014
The Problem
5
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The Problem
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Clinical Trials
EMA
Ap
pro
val f
or
Sale
HTA
Ap
pro
val
Phase 1 Phase 2 Phase 3
5,000
10,000
Compounds
250
Compounds
3 – 6 Years 6 – 7 Years
5
Therapies
1
Therapy
2 – 5 Years
Number of Patients/Subjects
20-100 100-500 1000-5000
Regulatory Review
Drug Discovery
Pre Clinical Testing
PhV
Monitoring
Total Cost: ~$2 Billion USD
Sources: Drug Discovery and Development: Understanding the R&D Process, www.innovation.org;
CBO, Research and Development in the Pharmaceutical Industry, 2006;
Forbes, Matthew Herper, “The Truly Staggering Cost Of Inventing New Drugs”, February 10, 2012
Current EU trial pathways are expensive and slow
New EU therapies don’t reach
patients until here
Real World Evidence - Health Databases
8
Time of recruitment represents about 30% of total CT Time - roughly 30 months of development
Months
0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
Start-up Recruitment Time Trial Time Data Clean-up & Report
Phase 3
Phase 2
Phase 1
30% of Clinical trial 30 months in total
9 © Copyright Vital Transformation - 2014
Source: CMR International. Pharmaceutical R&D Factbook 2011, Thomsom Reuters, May 2011
Current development times by clinical area
(1) Target indications of the project FDIH = First-dose in Humans, here considered before Phase 1 Source: CMR International. Pharmaceutical R&D Factbook 2011, Thomsom Reuters, May 2011
0 1 2 3 4 5 6 7 8 9 10
New Chemical entity
New Biological Entity Toxicity to FDIH
Phase 1
Phase 2
Phase 3
Submission
Years
0 1 2 3 4 5 6 7 8 9 10
Cardiovascular
Anti-Cancer
Central Nervous System
Toxicity to FDIH
Phase 1
Phase 2
Phase 3
Submission
Years
10 © Copyright Vital Transformation - 2014
Three queries from clinicaltrials.gov were selected to test databases Alzheimer’s Disease
Cardiovascular disease
Inclusion criteria Male and Female > 18 years Diagnosis of NSCLC Stage IIIB not amenable to curative treatment or Stage IV. No prior chemotherapy for lung cancer. Patients must have at least one uni-dimensionally measurable lesion. Prior radiation therapy to less than 25% of bone marrow, whole pelvis not allowed. Radiation must be completed at least 4 weeks prior to study enrollment.
Exclusion Criteria: Treatment with any drug within the last 30 days that has not received regulatory approval. Serious cardiac condition. Serious medical disorder in addition to NSCLC that would make it difficult for the patient to complete the study. Inability or unwillingness to take folic acid or Vitamin B12 supplementation. Presence of fluid retention that cannot be controlled by drainage.
Inclusion Criteria Male and Female >50 Probable or possible Alzheimer's disease Living in skilled nursing home Exclusion Criteria Other types of dementia, psychiatric or neurologic disorders Musculoskeletal disease
Inclusion Criteria Male and Female >18 years Must be on background lipid lowering treatment. Must be at high risk of a CV event. Must have an LDL C >/=70 mg/dL (1.8 mmol/L) and < 100 mg/dL (2.6 mmol/L) or OR, Must have non-HDL-C >/= 100 mg/dL (2.6 mmol/L) and < 130 mg/dL (3.4 mmol/L)
Exclusion Criteria An LDL C < 70 mg/dL (1.8 mmol/L) or >/= 100 mg/dL (2.6 mmol/L) or non HDL-C < 100 mg/dL (2.6 mmol/L) or >/=130 mg/dL (3.4 mmol/L) Planned coronary (PCI or CABG) or other arterial revascularization. New York Heart Association Class IV congestive heart failure or left ventricular ejection fraction < 25% by cardiac imaging. Chronic renal insufficiency with creatinine clearance of <30 ml/min/1.73m^2 by MDRD formula or with end state renal disease on dialysis. History of hemorrhagic stroke.
Non-Small Cell Lung Cancer
We studied these queries in three data systems that can be classified into two groups
Region # Patients in
Database Healthcare
setting Year created
Databases with electronic patient records*
CPRD – TrialViz UK 4.6 M GPs 2012
Penn Medicine – Oracle Health Science Network US 2.25 M Hospitals 2013
Databases led by patients(*)
Patients-Know-Best UK 150k Hospitals 2012
* Data is Anonymised/De-identified
Results CPRD – Trial Viz
Alzheimer disease: Result of Query with CPRD
Geographical Distribution of Hits Distribution of # of patients per practice
# of patients per practice
Inclusion Criteria
Male and Female >50
Probable or possible Alzheimer's disease
Living in skilled nursing home
Exclusion Criteria
Other types of dementia, psychiatric or neurologic disorders
Musculoskeletal disease
Number of Patients identified: 1,353
Query results – Anonymised Data
Alzheimer’s CPRD Penn
Medicine
Patients identified in query 1,343 890
Acceptance Rate Based on Historical Averages 60% (1,2) 60% (1,2) Total Patients Needed in
in Clinical Trials.gov
Total Potential Patient Trial Pool 670 445 249 (3)
(1) Avalon L. Am J Geriatr Psychiatry. 2009 Jan;17(1):65-74 (2) Fouad MN. et al. J Oncol Pract. 2013 Mar;9(2):e40-7 (3) Number of patients needed in entire trial (world wide) (4) Number of trial sites used in the actual trial
(*) Data shown in previous slide
11 (*) 1 53 (4)
Total Trial Locations Registered
in Clinical Trials.Gov
Total Implied Locations Required using revised
Data Base Search
Result of Query with CPRD: Cardiovascular Disease
Geographical Distribution of Hits Distribution of # of patients per practice
Inclusion Criteria Male and Female >18 years
Must be on background lipid lowering treatment. Must be at high risk of a CV event. Must have an LDL C >/=70 mg/dL (1.8 mmol/L) and < 100 mg/dL (2.6 mmol/L) or OR, Must have non-HDL-C >/= 100 mg/dL (2.6 mmol/L) and < 130 mg/dL (3.4 mmol/L).
Exclusion Criteria An LDL C < 70 mg/dL (1.8 mmol/L) or >/= 100 mg/dL (2.6 mmol/L) or non HDL-C < 100 mg/dL (2.6 mmol/L) or >/=130 mg/dL (3.4 mmol/L) Planned coronary (PCI or CABG) or other arterial revascularization. New York Heart Association Class IV congestive heart failure or left ventricular ejection fraction < 25% by cardiac imaging. Chronic renal insufficiency with creatinine clearance of <30 ml/min/1.73m^2 by MDRD formula or with end state renal disease on dialysis. History of hemorrhagic stroke.
Number of Patients identified: 136,053
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Query Results – Anonymised Data
Cardiovascular CPRD Penn
Medicine
Patients identified in query 136,065 982
Total Patients Needed in Clinical Trials.gov Acceptance Rate 10% (1) 10% (1)
Total Patient Trial Pool 13,065 98 650 (2)
(1) Harper D. B. ”Projecting realistic enrolment rates”. Monitor, Winter 2004, pages 15-18 (2) The clinical trial included 12,000 patients world-wide. Based on the number of hospitals in the UK and the rest of the world, 650 patients were
allocated in the UK (3) The clinical trial required and registered 461 trial locations. Assuming the acceptance rate to be the same world-wide, 24 locations were allocated
in UK
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7(*) 7 (**) 24 (3)
Total Implied Locations Required using revised
Data Base Search
Total Trial Locations Registered
in Clinical Trials.Gov
(*) Data shown in previous slide, (**) Number extrapolated, assuming all locations have ths same number of patients (i.e. 98)
Query Results – Anonymised Data
(1) Harper D. B. ”Projecting realistic enrolment rates”. Monitor, Winter 2004, pages 15-18 (2) The clinical trial included 12,000 patients world-wide. Based on the number of hospitals in the UK and the rest of the world, 650 patients were
allocated in the UK (3) The clinical trial required and registered 461 trial locations. Assuming the acceptance rate to be the same world-wide, 24 locations were allocated
in UK
© Copyright Vital Transformation - 2014
Why is there a difference of two orders of magnitude between CPRD and Penn Medicine?
CPRD is GP data, Penn Medicine is hospital/outpatient/pharmacy data
Very few CVD patients go to the hospital every two years
(*) Data shown in previous slide
CPRD and Penn Medicine differ in population base, offering a different number of patients and depth of information
Patients with Lipid Lowering Treatment
Patients with LDL > 1.8 & <2.6
Patients without Renal Failure OR stroke
Patients without CABG or PCI
CPRD (5M patients)
Penn Medicine
(2.3M Patients)
CPRD captures general population Penn Medicine captures patients
CPRD offers a broad patient set, but without hospital data UPenn offers a narrow patient set with precise hospital data
Included patients Excluded patients
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(*) All data obtained ar UPenn and CPRD was de-identified
Query results – Anonymised Data
(1) Madsen L.T. et al. J Natl Compr Canc Netw. 2014 Jul;12(7):993-8,
(2) Pauporte. I. J Clin Oncol 31, 2013 (3) World-wide values
Non-Small Cell Lung Cancer CPRD Penn
Medicine
Patients identified in query 0 262
Acceptance Rate 45% (1,2) 45% (1,2) Total Patients Needed in Clinical Trials.gov
Total Patient Trial Pool 0 118 1,713 (3)
© Copyright Vital Transformation - 2014
N/A 15 134 (3)
Total Implied Locations Required using revised
Data Base Search
Total Trial Locations Registered
in Clinical Trials.Gov
Patient Led Databases
20
© Copyright Vital Transformation - 2014
• Survey was ran in partnership with two practitioners currently using the Patients Know Best platform
• Number of patients invited to participate in survey: 540
• Number of patients who took survey, 161
• Survey run in Fall 2014
• Confidence 95%, Margin= ± 5 % (80/20)
Survey
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Yes 83%
No 17%
Do you or a member of your family have a chronic condition for which there is
currently no therapy or cure?
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Yes 92%
No 8%
Would you be willing to share your medical health records (data) to help researchers find
needed new therapies and cures?
© Copyright Vital Transformation - 2014
Yes 73%
No 27%
Would you be willing to participate as a research subject by taking new therapies to see if they work?
© Copyright Vital Transformation - 2014
Patient-led databases can deliver a targeted result in specific disease areas
Population Men & Women >50 with risk of
Alzheimer’s
Final after inclusions and
exclusions
Acceptance Rate
Total Patients
Current CPRD 4.6 million 14,872 1,343 60% 670
Current Penn Medicine 2.25 million 4,549 890 60% 534
Theoretical Patient-Led Model in Alzheimer's
3,783 341 73% 249 (*)
(*) Number of patients needed in test Alzheimer trial = 249 Assumption: Patient-led database captures a population identical to (1) CPRD and (2) Penn Medicine
Impact on Time Needed to Bring
New Medicines to Patients
26 © Copyright Vital Transformation - 2014
Databases can reduce time of indentifying a patient
Current recruitment (Phase 3)
9 months 3 months
Identification Sign-in
Recruitment with Database X months 3 months
Identification Sign-in
Total Time Saved
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Impact of faster identification on R&D time of patients receiving cardiovascular medicines
Current 25% Reduction 50% Reduction 100% Reduction
Phase 1 (yrs) 1.8 1.8 1.8 1.8
Phase 2 (yrs) 3.3 3.1 3.0 2.6
Phase 3 (yrs) 3.1 2.9 2.8 2.4
Total (yrs) 8.2 7.9 7.5 6.8
28 © Copyright Vital Transformation - 2014
Time
(years)
Phase 3
Phase 2
Phase 1
Industry Average R&D times for Cardiovascular drugs
Comment: “Reduction” means reduction of identification time
Impact of faster identification on R&D time of patients receiving Cancer drugs
Current 25% Reduction 50% Reduction 100% Reduction
Phase 1 (yrs) 2.4 2.4 2.4 2.4
Phase 2 (yrs) 3.3 3.1 3.0 2.6
Phase 3 (yrs) 3.1 2.9 2.8 2.4
Total (yrs) 7.4 7.0 6.8 6.0
29 © Copyright Vital Transformation - 2014
Time
(years)
Industry Average R&D times for Cancer drugs
Comment: “Reduction” means reduction of identification time
Phase 3
Phase 2
Phase 1
Impact of faster identification on R&D time of patients receiving Alzheimer drugs
Current 25% Reduction 50% Reduction 100% Reduction
Phase 1 (yrs) 1.8 1.8 1.8 1.8
Phase 2 (yrs) 2.7 2.5 2.4 2.0
Phase 3 (yrs) 2.7 2.5 2.4 2.0
Total (yrs) 7.2 6.8 6.6 5.8
30 © Copyright Vital Transformation - 2014
Time
(years)
Industry Average R&D times for Alzheimer drugs
Comment: “Reduction” means reduction of identification time
Phase 3
Phase 2
Phase 1
ROI for Saving Time – Calculating the Value
31 © Copyright Vital Transformation - 2014
Patient databases significantly impact the business case of a drug
Reduces R&D time
Reduces number of recruitment sites
Reduces costs of Recruitment Process
Reduces Cost of Capital
Adds Sales (longer time in the market under patent protection)
Comment: This presentation does not consider reduction of recruitment costs (B), due to lack of consistent data.
Patient Databases
The impact of time on Cost of Capital: an example
Investor puts 10 M$
Annual rate of return: 10% Investor requires 20M$
7 years
5 years
Investor requires 16 M$ Investor puts 10 M$
Annual rate of return: 10%
By cutting time,
you save
4 M$
in cost of capital
R&D Project A
R&D Project B
5 years
Investor requires 32 M$ Investor puts 10 M$
Annual rate of return: 10%
Project B with failure rate of 50%
BUT,… Investors also consider risk of failure
Failures raise the average development cost of a marketed drug from 215M$ to 0.9-2.3b$
Phase 1 Phase 2 Phase 3 CT Cost per
Drug
Average Cash (Direct) Cost of Clinical R&D (a) 16 M$ 42 M$ 158 M$ 215 M$ (1)
(1) Cost per drug approved, industry average (2) Cost of Capital = 11% (3) Current time to market from slide 28-30
Probability of Success (b)
CT Cost of Marketed Drug (2,3)
Cardiovascular 13% 24% 74% 1,025 M$
Anti-Cancer 17% 26% 62% 880 M$ (c)
Central Nervous System 5% 9% 33% 2.365 M$
(a) Paul, S.M. et al. (2010), Nature Reviews Drug Discovery. 9(3), 203-214 (b) CMR International. Pharmaceutical R&D Factbook 2011, Thomsom Reuters, May 2011 (c) Cancer drugs are substantially more expensive to develop than $215 mil, and have a higher
success rate due to programmes such as conditional approval due to unmet medical need.
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Estimated impact for cost of capital in CVD
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Current Reduction 25% Reduction 50% Reduction 100%
Phase 1 (yrs) 1.8 1.8 1.8 1.8
Phase 2 (yrs) 3.3 3.1 3.0 2.6
Phase 3 (yrs) 3.1 2.9 2.8 2.4
Total time (yrs) 8.2 7.9 7.5 6.8
Time saved (months) - 3.6 8.4 16.8
Cost of R&D 1,025 M$ 995 M$ 965 M$ 910 M$
R&D Savings - 30 M$ 60 M$ 115 M$
(1) Success rates are included in these calculations (2) Including cost of capital: 11%
Estimated impact for cost of capital in Cancer drugs
© Copyright Vital Transformation - 2014
Current Reduction 25% Reduction 50% Reduction 100%
Phase 1 (yrs) 2.4 2.4 2.4 2.4
Phase 2 (yrs) 2.8 2.6 2.5 2.1
Phase 3 (yrs) 2.2 2.0 1.9 1.5
Total (yrs) 7.4 7.0 6.8 6.0
Time Saved (months) - 4.8 7.2 16.8
Cost of R&D 880 M$ 855 M$ 830 M$ 785 M$
R&D Savings - 25 M$ 50 M$ 95 M$
(1) Success rates are included in these calculations (2) Including cost of capital: 11%
Estimated impact for cost of capital in Alzheimer’s
(1) Success rates are included in these calculations (2) Including cost of capital: 11%
© Copyright Vital Transformation - 2014
Current Reduction 25% Reduction 50% Reduction 100%
Phase 1 (yrs) 1.8 1.8 1.8 1.8
Phase 2 (yrs) 2.7 2.5 2.4 2.0
Phase 3 (yrs) 2.7 2.5 2.4 2.0
Total (yrs) 7.2 6.8 6.6 5.8
Time saved (months) - 4.8 7.2 16.8
Cost of R&D 2,365 M$ 2,295 M$ 2,225 M$ 2,095 M$
R&D Savings - 70 M$ 140 M$ 270 M$
Saving time reduces cost of capital by 4-10% per phase of clinical trial costs (*)
© Copyright Vital Transformation - 2014
Savings in Cost of Capital
(as % of R&D spending per trial)
Expected time saved
with Databases
Comment 1: Average time of conducting CT differs by phases, so does cost-of-capital (*) Savings of Cost of Capital computed when the drug is NDA ready
0%
4%
8%
12%
16%
0 2 4 6 8 10 12
Phase 3
Phase 2
Time Saved
(Months)
Savings in cost-of-capital are driven by identification time
© Copyright Vital Transformation - 2014
Variable Range Variation about
centre value Centre value
Reduction of Identification time 25 – 75% ± 50% 50%
Sign-in time 4.5 – 1.5 months ± 50% 3 months
WACC 9 – 13% ± 2% points 11%
Average cost of Phase 1 trial per drug 8 – 24 M$ ± 50% 16 M$
Average cost of Phase 2 trial per drug 21 – 63 M$ ± 50% 42 M$
Average cost of Phase 3 trial per drug 76 – 228 M$ ± 50% 152 M$
60 M$ 70 M$ 80 M$ 90 M$ 50 M$ 40 M$ 30 M$
Savings of Cost of Capital in industry-wide R&D spending per marketed drug (Cardiovascular case)
Identification time
Sign-up time
WACC
Cost of Phase 1
Cost of Phase 2
Cost of Phase 3
MAPPs and Real World Patient Databases
40 © Copyright Vital Transformation - 2014
NRDD vol. 10, July 2011
Initial narrow license,
small targeted
population with clear
bio-marker
Progressively include larger populations including
marker negative
Medicines Adaptive Pathways to Patients (MAPPS)
Managing uncertainty:
1. Starts by targeting the most likely to respond
2. All key stakeholders (patients, regulators, practitioners, industry) are aligned with the process starting at the design stage
3. Robust capture of real-time data of the actual trial experience
Conclusions
42 © Copyright Vital Transformation - 2014
© Copyright Vital Transformation - 2014
1. Real World Evidence from GP, hospital and patient-led databases has the potential to reduce the time to bring needed new medicines to patients.
2. The strategy of database development should combine Hospital Data, GP Data, and Patient Led datasets; this provides the greatest flexibility and depth of data.
3. Patient Databases can support the evolving data required in support of MAPPs pathways to develop a more efficient approval process
4. The data sharing draft legislation passed by the European Parliament in March of 2014 puts at risk the use of Anonymised national patient databases in the EU; R&D will follow the path of least resistance
Duane Schulthess Managing Director
www.vitaltransformation.com
Copyright Vital Transformation - CONFIDENTIAL
QUESTIONS?
Appendix
45 © Copyright Vital Transformation - 2014
The full development of a drug for heart diseases costed about 3b$, while for obesity and diabetes 150-300 M$
© Copyright Vital Transformation - 2014
Average cost of developing one drug for… (1,2) Phase 1 Phase 2 Phase 3 Total
Obesity 2.3 M$ 22 M$ 253 M$ 277 M$
Diabetes 0.6 M$ 13 M$ 143 M$ 157 M$
Heart Disease 1.8 M$ 172 M$ 2,854 M$ 3,028 M$
(1) Roy A.S. Stifling new cures: the true cost of lengthy clinical drug trials. Project FDA report, Manhattan Institute for Policy Research No5 (2012) (http://www.manhattan-institute.org/pdf/fda_05.pdf)
(2) Excluding failure rates
Cost of developing a drug for heart diseases is about 10X that of developing drugs for other cardiovascular diseases
© Copyright Vital Transformation - 2014
Obesity Phase 1 Phase 2 Phase 3 Total
Lorquess 2.3 M$ 38 M$ 368 M$ 408 M$
Qnexa - M$ 7 M$ 177 M$ 184 M$
Contrave - M$ 23 M$ 214 M$ 237 M$
Diabetes
Byetta 1.1 M$ 9 M$ 68 M$ 78 M$
Bydureon 0.4 M$ 4 M$ 152 M$ 156 M$
Victoza 0.4 M$ 27 M$ 210 M$ 237 M$
Heart Disease
Xarelto 1.1 M$ 207 M$ 2,866 M$ 3,074 M$
Eliquis 2.5 M$ 137 M$ 2,842 M$ 2,981 M$
(1) Roy A.S. Stifling new cures: the true cost of lengthy clinical drug trials. Project FDA report, Manhattan Institute for Policy Research No5 (2012) (http://www.manhattan-institute.org/pdf/fda_05.pdf) (2) Excluding failure rates