Transcript Document

Securing an Adequate Drug
Supply for each TB Patient
Jennifer Flood MD, MPH
University of California, San Francisco
[email protected]
1
Essential Components of a National
TB Program
International Standards for TB Control programs
– An uninterrupted supply of good quality anti-TB drugs
Essential Components of a Tuberculosis Prevention and
Control Program, ACET
• Ensure patients who have TB receive appropriate
treatment until they are cured
• Treat patients without consideration of their ability
to pay
2
Background
Why are we discussing in 2012?
• TB patients and U.S. programs have
experienced recurring difficulty accessing MDR
TB drugs
Issues:
• Drug shortages
• Climbing costs
• Multi-step processes for procurement
• Out-of-reach for uncovered patients
3
2010 NTCA Survey:
Interruptions in TB Drug Supply
• 21 of 33 (64%) faced challenges obtaining
MDR drugs in the United States
• 95% experienced barriers due to a
nationwide shortage
• 62% indicated drugs too expensive fro
program
4
TB Drug Shortages since 2005
•
•
•
•
•
•
•
5
INH
Rifabutin
Rifapentine
Amikacin
Capreomycin
Kanamycin
Streptomycin
cycloserine
ethionamide
cycloserine
What factors impede MDR TB drug
access?
6
The Short List:
• Single manufacturer for most TB drugs
• Drug not profitable and not prioritized for
production
• FDA inspection overseas pending
• Materials to make drug in short supply
• Not FDA approved, requires lengthy IRB
investigational drug (IND) process
• Drugs have very short time to expiration
• Cost of drugs puts drug out of reach
Which drugs have a tenuous supply?
Drugs
Amikacin
Capreomycin
7
Reason for supply barriers
materials short for production
overseas FDA inspection pending
company change  huge cost increase
Cycloserine
company changecost increase
Clofazimine
manufacturing halted;
restricted to Hansen’s disease
requires IND /IRB for each patient
How much does an MDR TB treatment
regimen cost?
Drug
Capreomycin
Linezolid
Levofloxacin
Cycloserine
Ethionamide
•
•
•
Cost per dose
No. doses
$136.00*
$50.30
$29.9
$14.76
$10.38
137**
790
790
790
790
$18,632
$39,737
$23,621
$11,661
$8,200
8 months of above multidrug regimen with injectable
Followed by regimen without injectable X 18 months
Assumes culture conversion at 3 months (treatment: 24 mos. post conversion)
TOTAL MDR TB DRUG COSTS:
$ 56,049 (340 B clinic) or
$101,851
(common hospital)
____________________________________________________________
Pricing Source: 2011 California and Nevada local health departments
*Cost varies : $136.00 per 1 gram vial to $350 for 1 gram vial
**Injectable given 5 days/week X3.5 months; 3 days/week X 4.5 months
8
Total cost
Less expensive regimen*
Amikacin
$630
Levofloxacin
$15,721
Ethionamoide
$6,952
Ethambutol
$2048
PZA
$2212
_______________________________
TOTAL:
$27,490
*No linezolid or capreomycin; common hospital
cost
9
Who cannot afford TB treatment?
Patients with MDR TB
• Working with co-pay or limit
• Not covered: students, temp workers,
undocumented
• Indigent, not Medi-caid eligible
Programs
• Drug costs larger than TB programs’
budget
10
Procedure to obtain Clofazimine
•
•
•
•
•
Patients to fill out a “simple form “
Provider completes application through hospital IRB
Submits individual IND to FDA for patient requiring drug
Required Documents
FDA Forms:
–
–
–
–
•
•
•
•
Doctor's CV
Current lab results for patient (CBC, chem, sensitivity data)
Signed informed consent document
IRB approval letter
–
•
•
•
•
11
Form FDA 1571 (PDF) Ι Form FDA 1571 Instructions
Form FDA 1572 (PDF) Ι Form FDA 1572 Instructions
Form FDA HFD-590 (DOC)
Download forms from the FDA's Official Website
For your information - Clofazimine Treatment Protocol
Once IRB approved
send forms to FDA
Once approved, clofazamine provided to patient through Hansen's Division/Novartis
free of cost
Usually takes about 10-14 days from time FDA receives fax to arrival of clofazimine
Do TB drug shortages affect patient
outcomes?
National TB Controllers survey:
• 58% of respondents reported that drug
shortages led to treatment delays
• 32% reported treatment lapses
• 26% reported changing to less optimal
regimen
12
Who pays? Impact of interrupted
supply of MDR TB Drugs
• Impact felt by patient, programs, providers
• Lack of access to optimal drug regimen can lead
to further drug resistance
• Prolonged infectiousness
• Increased spread
• Poorer outcomes for patients
13
Example 1
• 26 yo on work visa from European country
with high MDR/XDR incidence
• Smear negative, culture-positive cavitary
MDR TB diagnosed 2 wks prior to travel
• Given 10 day supply of medications
through Green Light Committee
• Told by physician- not to worry because
“TB medications are free everywhere in
the world”
14
Example 1 -continued
• On arrival smear positive
• Patient had employer insurance but payment disallowed
given pre-existing condition
• Prescribed initial regimen but capreomycin cost to
program = $140.00/dose
• Unable to afford drug regimen, in addition to MD, nurse
care, DOT, isolation
• Patient on MDR drugs without injectable ~ 2 weeks
• Receiving jurisdiction reports ~10 TB cases/year
• Through diplomatic channels, arranged delivery of GLC
medications from originating country
15
Example 2: The perfect storm
• County X reports ~6-10 MDR TB
cases/year
• All MDR TB patients need injectable agent
• Given price of capreomycin, this county
changed regimen and pharmacy contract
to amikacin
• When amikacin had protracted shortage,
TB controller became concerned
16
Steps for TB programs:
Securing drugs for your patient
1) Ask pharmacy to check with other
distribution centers/wholesalers
2) Call manufacturer directly
1) Is drug in stock?
2) How can it be obtained? – through wholesalers
or directly from manufacturer
3) If drug is on allocation (requires special request )
4) Is drug short-dated?
5) If out of stock, anticipated date available?
3) Contact local hospitals to share supply
17
Requirement: Lot’s of time
1)Maintain contacts
•
Distributers and manufacturers
•
Customer service and hospital team
2)Staff time
Hands-on, time-intensive, shoe-leather
telephone/email investigation
3)Track and maintain
Up-to-date information on drug availability
18
How to Maintain a
Strong Regimen when
drug supply is interrupted?
Injectable:
• Replace with alternate injectable, if can
Quinolone:
• Use less expensive of levoflox or moxiflox
Add to oral agents:
• linezolid, clofazamine, cycloserine, PAS,
ethionamide
19
Response to Drug Shortages
• Not a new problem (ref. 1994 IUATLD)
• Multiple agencies, programs, individuals
exert effort to resolve
• Response has been case by case
• Time from shortage detection to drug
reaching patient is long
20
FDA Drug Shortage Website
http://www.fda.gov/drugs/drugsafety/drugsh
ortages/ucm050792
[email protected]
21
2011 President’s Executive Order
President Obama issued Executive Order
directing FDA and Dept. of Justice to:
– Broaden reporting of manufacturing
discontinuations
– Expedite FDA regulatory review if help avoid
a shortage
– Report to Department of Justice if FDA finds
price gauging or illegal stockpiling
22
Possible Solutions
• Central mechanism for accessing drugs
– Federal drug stockpile (eg. Botulism anti-toxin)
– Centralized IRB mechanism for old drugs
– Streamlined process to obtain investigational drugs
for compassionate use
• Remove cost as barrier for all patients/programs
– Remove copays
23
Expedite Investigational Drug
Process
• Secure centralized IRB
– National (CDC
– In place in some states (eg California,Texas)
• Reduce burden of stepwise process and
secure more rapidly for individual patients
24
More Direct Solutions
Access
• Direct support of TB and MDR TB drug
production
• Distribute drugs
• Track supply, demand, and distribution
Cost
• Expand entitlement and adopt model of
HRSA HIV drug access (eg TB medi-caid
for all TB patients)
25
Advisory Council on Elimination
of TB
• MDR Workgroup charged to describe
extent of problem and potential
interventions
– Survey conducted
– Problem statement and fact sheet created
• ACET Resolution
– Identify interventions that ensure each TB
patient has uninterrupted supply of TB
treatment in U.S.
26
Acknowledgements
•
•
•
•
27
ACET MDR TB Working Group
California MDR TB Service
Lee Reichman MD
Ann Cronin
When Drugs are Hard to Come By:
Obstacles for Patients Receiving
TB Treatment in the United States
28
Drug Shortages in the United States
• The number of drug shortages annually
has tripled from 61 in 2005 to 178 in 2010.
• Many drugs in short supplyare sterile
injectables
• More than 90% of US hopsitals in June
2011 reported drug shortage in previous 6
months
29
Manufacturer Contacts:
Injectable agents
CAPREOMYCIN
Akorn: 800-932-5676
ask for hospital team,
drug is on allocation,
must complete request form
30
Injectable Access continued
STREPTOMYCIN
X-Gen 607-562-2700
• Available by wholesalers and distribution centers
AMIKACIN
Teva(short supply) and Bedford(none)
Teva: 800-545-8800
• For drop shipment
31
Tuberculosis and Drug Shortages
Medications
June 2011
July 2011
Sept 2011
Oct 2011
Kanamycin
Streptomycin
Amikacin
Capreomycin
Levofloxacin
Moxifloxacin
Cycoloserine
PAS
Ethionamide
Linezolid
Clofazamine
Red = Unavailable, Orange = Allocation on emergency basis only, Yellow = Short dated or
not available at wholesalers, Green = Available, Purple = Investigation Drug requires prior
authorization
What are the challenges to an uninterrupted supply
of anti-TB medications?
Medications
Challenges to an uninterrupted supply
Kanamycin
No US manufacturer
Streptomycin
Sole US manufacturer; increased demand cause for Aug/Sept
2011 shortage.
Amikacin
Materials short for production overseas FDA inspection pending
Capreomycin
PAS
Sole US manufacturer. Price increase x 10 since change in
manufacturer (2007: $11.7/1 gram vial; 2010: $137/1 gram vial
after the manufacturer changed from Eli Lily to Akorn; 2011:
New report of ~$300/1 gram vial)
Sole US manufacturer; price doubled when license transferred
from Eli Lily
Sole US manufacturer
Ethionamide
Not immediately available via wholesaler
Linezolid
Very expensive
Clofazamine
Requires IND and local IRB approval, process takes 8-10 wks
Cycoloserine