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ANTICIPATION AND ADAPTATION MINICASES
PHARMACEUTICALS, SOx, BSE, WMD
Lawrence McCray and Kenneth Oye
Massachusetts Institute of Technology
Prepared for Trans-Atlantic Uncertainty Colloquium
October 11-12, 2006
Washington, DC
Mini Cases on Adaptation and Anticipation with Slides
Pharmaceuticals
new drug approval and aftermarket reappraisal
crises => recommendations for planned adaptation
SOx and PM
late adaptation
compartmentalized regulation, emissions permit price
BSE
UK, EU, US and Japan
TSE Roadmap
Iraq WMD
UN 1441 as planned adaptation
or as US planned confirmation and French planned delay
Other Cases for Possible Discussion
CFC – Ozone
Molina model, ozone hole canary, Dupont-ICI interest
Air Safety – FAA NTSB
Post crash rapid assimilation and learning
Highway Safety – NHTSB
prospect of litigation and suppression of data
Food Safety
CDC USDA and HAACP
Diet – Transfats
Heart Association and NIH to Present Dietary Standards
SUMMARY OF MAIN POINTS
The Issue: Protecting the public from adverse effects of already-approved drugs
How We Anticipate: We require expensive clinical trials prior to approval.
Pre-approval trials - expose hundreds of mostly healthy individuals for short periods
Post approval use - millions of exposures of less healthy people for long periods
How we Adapt:
Post-marketing surveillance program [PMS] at the FDA
Add-on “Phase 4” trials after formal approval
Is it Working?
FDA PMS program thought to catch under 2% of adverse effects [weak incentives]
~100,000 die of adverse effects in US hospitals each year
Big awkward failure cases: Vioxx, depressants and teen suicide, etc.
Only a fraction of Phase 4 studies done, and FDA unconcerned
Further Improvements?
De novo review studies each 5 years? [EU policy, US proposal]
A new review authority outside FDA? [New England Journal of Medicine]
Type I and Type II Errors on Drug Approval
IF delay or deny approval of drug that is efficacious and safe…..
IF approve drug that is unsafe or ineffective…..
Tilt toward acceptance of Type I or Type II error depending on context.
But uncertainty will be substantial, one CANNOT know …..
Detection, learning and adaptation
Improve after market surveillance
Improve analytic capacity for integrating information
Reduce organizational impediments to acting on information
FDA Vioxx
Advisory
August 19, 1991
CRISIS WITH
HEADLINES AND
LITIGATION
November 3, 1997
IOM
RECOMMENDS
PLANNED
ADAPTATION
September 30, 2004
September 26, 2006
CRISIS WITH
HEADLINES AND
LITIGATION
IOM
RECOMMENDS
PLANNED
ADAPTATION
TRIAZOLAM: ANTICIPATION AND ADAPTATION - ROUND ONE
TRIAZOLAM OR HALCION ™ IS A SEDATIVE WITH SHORT HALF LIFE
UK + US DIFFER ON CERTIFICATION
70‘s 80‘s UK AND US CERTIFIED EFFICACY AND SAFETY AT .5 MG DOSE
90‘s US CERTIFIED -- SAFE AND EFFICACIOUS AT .25 MG DOSE
90‘s UK WITHDREW -- NOT SAFE .AT 5 MG NOT EFFICIOUS AT .25 MG
EVIDENCE ON PSYCHOTIC SIDE-EFFECTS
• INITIAL CLINICAL TRIALS
• SECOND ROUND CLINICAL TRIALS
• MURDER CASE WITH HALCION DEFENSE
• POSTMARKET SPONTANEOUS REPORTS
Source: Abraham and Sheppard
UK SPONTANEOUS REPORTS PSYCHIATRIC REACTIONS BY YEAR
FOR SPECIFIC BENZODIAZEPINES PER MILLION PRESCRIPTIONS
1979 1980 1981 1982 1983 1984 1985 1986
Triazolam 114.0 44.0 14.0 43.0 20.0 5.5
1.8
2.5
Flurazepam 0.9
0.9
0.4
1.3
0.5 0.0
2.2
0.0
Nitrazepam 0.1
0.9
0.5
0.0
0.3 0.0
0.8
0.4
Temazepam 4.1
4.5
3.7
1.9
2.2 1.7
1.3
0.4
Lorazepam 2.4
3.3
1.4
2.0
4.3 1.9
6.7
1.9
Diazepam 0.4
0.7
0.1
0.1
0.2 0.4
0.4
1.0
1979 1980 1981 1982 1983 1984 1985 1986
Triazolam 114.0 44.0 14.0 43.0 20.0 5.5
1.8
2.5
Flurazepam 0.9
0.9
0.4
1.3
0.5 0.0
2.2
0.0
Nitrazepam 0.1
0.9
0.5
0.0
0.3 0.0
0.8
0.4
Temazepam 4.1
4.5
3.7
1.9
2.2 1.7
1.3
0.4
Lorazepam 2.4
3.3
1.4
2.0
4.3 1.9
6.7
1.9
Diazepam 0.4
0.7
0.1
0.1
0.2 0.4
0.4
1.0
PSYCHIATRIC EPISODES IN CLINICAL TRIALS
INITIAL UPJOHN TRIALS
REPORTED
Placebo
2
Triazolam
1
1979 1980 1981 1982 1983 1984 1985 1986
Triazolam 114.0 44.0 14.0 43.0 20.0 5.5
1.8
2.5
Flurazepam 0.9
0.9
0.4
1.3
0.5 0.0
2.2
0.0
Nitrazepam 0.1
0.9
0.5
0.0
0.3 0.0
0.8
0.4
Temazepam 4.1
4.5
3.7
1.9
2.2 1.7
1.3
0.4
Lorazepam 2.4
3.3
1.4
2.0
4.3 1.9
6.7
1.9
Diazepam 0.4
0.7
0.1
0.1
0.2 0.4
0.4
1.0
REPORTED
Placebo
2
Triazolam
1
ACTUAL
1
7
1979 1980 1981 1982 1983 1984 1985 1986
Triazolam 114.0 44.0 14.0 43.0 20.0 5.5
1.8
2.5
Flurazepam 0.9
0.9
0.4
1.3
0.5 0.0
2.2
0.0
Nitrazepam 0.1
0.9
0.5
0.0
0.3 0.0
0.8
0.4
Temazepam 4.1
4.5
3.7
1.9
2.2 1.7
1.3
0.4
Lorazepam 2.4
3.3
1.4
2.0
4.3 1.9
6.7
1.9
Diazepam 0.4
0.7
0.1
0.1
0.2 0.4
0.4
1.0
REPORTED
Placebo
2
Triazolam
1
ACTUAL
1
7
SECOND UPJOHN TRIALS
Placebo
Other drugs
Triazolam
REPORTED
0.5 %
1.9 %
9.9 %
OUTCOMES ROUND ONE
UK AND EU COMMITTEE ON PROPRIETARY MEDICAL PROCEDURE BAN TRIAZOLAM
US FDA ADVISORY COMMITTEE: VOTED 7 TO 1 “SAFE AND EFFECTIVE” AT .25 MG
Differences
UK
US
Integration of
data
Integration of initial studies,
Consideration of each source of
clinical trials, post market data information in isolation
Committee
Members
Medical Generalists
Specialists in pharmacology
Organizational
structure
Licensing & post-licensing
by different orgs and people
Licensing & post-licensing
by same org and people
Conflicts of
interest on
committee
None
9 of 11 received grants from Upjohn
1 of 11 was Upjohn stockholder
7 of 8 voters need FDA C of I waivers
⇒ What outcomes do you prefer and why?
⇒ What factors appear to be most important in explaining outcomes?
TRIAZOLAM: ANTICIPATION AND ADAPTATION - ROUND TWO
The United Kingdom, Brazil, Argentina, Norway, and Denmark removed Halcion
from the market, and Upjohn withdrew Halcion from the market in Netherlands.
The United States and Canada modified drug labeling to reduce the
recommended dose and duration of treatment and to heighten awareness of
possible side effects. Yet different data and analyses have resulted in conflicting
messages that are difficult to reconcile and interpret.
Public concern rises....
ROUND TWOANTICIPATION AND ADAPTATION - ROUND TWO
TRIAZOLAM:
The United Kingdom, Brazil, Argentina, Norway, and Denmark removed Halcion
from the market, and Upjohn withdrew Halcion from the market in Netherlands.
The United States and Canada modified drug labeling to reduce the
recommended dose and duration of treatment and to heighten awareness of
possible side effects. Yet different data and analyses have resulted in conflicting
messages that are difficult to reconcile and interpret.
Public concern rises and FDA responds
It’s the Most
Widely Prescribed
Sleeping Pill
In the World.
But Is It Safe?
1996 FDA Task Force
1. Concluded Halcion was "safe when prescribed according to current labeling“
and "effective in the treatment of insomnia at doses and durations currently
recommended in the labeling."
2. Recommended that a separate reassessment of the safety and efficacy of
Halcion be conducted by a panel of experts.
FDA asked the National Institute of Medicine (IOM) to assess:
• adequacy of designs and endpoints used in clinical trials of Halcion;
• quality and quantity of postmarketing data on adverse drug reactions;
• confidence in data on effectiveness, adverse events, and side effects
of Halcion at different doses and for different durations, including
those specified in the current product labeling; and
• need for additional studies on risk and efficacy of Halcion.
National Institute of Medicine conducts
study and issues recommendations
BOX 1 RESOURCES REVIEWED BY THE COMMITTEE
Premarketing clinical trial data (from the New Drug Application)
Data from FDA Psychopharmacological Drug Advisory Committee
International data
Integrated summaries of safety and efficacy
Postmarketing surveillance data
Spontaneous report data
Published literature
Use, sales, and prescription data
EFFICACY: Statistical reanalysis of data from trials using questionnaires to
evaluate the subjects' sleep clearly supports the previous analyses that
Halcion positively affects the quality of sleep. Polysomnographic data did
not exhibit evidence of tolerance over time. Additionally, the committee
found that a dose-response relationship does exist, and the literature
generally supports the claim that the drug is efficacious.
How can we reconcile the apparent discrepancy between the clinical
trial data and reports of adverse events related to the use of Halcion?
Some adverse events reported through the Spontaneous Reporting System
of FDA were similar to those that had been reported in early clinical trials
with higher doses and longer durations of use of Halcion. This, combined
with survey data that indicate that many people use hypnotic agents for
very long periods of time led the committee to consider the possibility that
adverse events reported for Halcion might be due, at least in part, to
the use of Halcion for longer periods of time and at higher doses than
those currently recommended in the labeling.
In general, the types and frequencies of reported adverse events are
subject to many external influences, including media attention,
marketing, litigation, differential reporting rates, ability to connect
drug use to a health event, and other factors, all of which affect the
accuracy of interpreting the results.
IOM RECOMMENDS CHANGES TO IMPROVE FDA ADAPTIVE CAPACITY
Recommendation 5: Improve Surveillance, Analysis, and Integration of
Findings. The committee recommends that FDA develop improved methods
for integrating the findings of clinical trials and postmarketing surveillance, and
for resolving discrepancies in the interpretation of data from spontaneous
reports, clinical case reports, and controlled clinical trials. This would include
the reestablishment of a biostatistics and epidemiology advisory
committee (in addition to having biostatistics and epidemiology
expertise on the other advisory committees) that would be charged with
the rapid and thorough assessment of the potential health risks
suggested by reports of adverse events, identification and resolution of
conflicts that may arise in the review of clinical trial and surveillance
data, and the provision of expert advice on the maintenance and
operation of effective postmarketing surveillance systems.
DRUG APPROVAL AND REAPPRAISAL
FUNDING SHARES FOR AFTERMARKET SURVEILLANCE DROPPING?
FDA Center for Drug
Evaluation and Research
Shrinking budget share
for aftermarket
surveillance and drug
safety
Rising budget
share for
new drug
approvals
New York Times 12/6/04
VIOXX RECALL
Approximately 15,000 bleeding ulcer deaths per year,
with COX2 inhibitors providing a significant benefit
in reducing deaths from bleeding.
Vioxx generates $2.5 billion in annual sales
Merck recalls Vioxx, then FDA issues advisory
- New research showed 2X risk of heart attack
- 1.5 % Vioxx vs .75 % placebo
Research from old Harvard, Vanderbilt University and
Merck clinical trials had revealed increased risk of
heart attacks and high blood pressure for Vioxx.
Because of inherent limitations in clinical trials, problems can lie hidden until drugs
go into wider use. "More than half of all drugs introduced have a new side effect ...
after approval with the current system.”
What motives did Merck have for voluntary recall, in advance of FDA action?
Did FDA balance need to bring drugs to market fast and to assess efficacy / safety?
FDA AFTERMARKET SURVEILLANCE AND LEARNING STILL WEAK?
"I would argue that the FDA as currently configured is incapable of protecting
America against another Vioxx. The scientific standards (the FDA) applies to
drug safety guarantee that unsafe and deadly drugs will remain on the U.S.
market.“
David Graham, FDA Associate Director of Drug Safety, November 2004
Senator Jeff Bingaman asked Graham to identify five (dangerous) drugs he
alluded to. Graham hesitated and then listed:
Crestor -- cholesterol-lowering drug
Meridia -- weight-loss drug
Bextra – painkilling drug
Accutane -- acne medication
Serevent -- asthma medication
INSTITUTE OF MEDICINE COMMISSIONED TO PRODUCT STUDY ON DRUG SAFETY
TASK STATEMENT DIRECTS EXPLICIT ATTENTION TO AFTER-MARKET SURVEILLANCE
After Vioxx
PREPUBLICATION
COPY OF IOM REPORT
ISSUED
SEPTEMBER 26, 2006
THE FUTURE OF DRUG SAFETY
INSTITUTE OF MEDICINE, DRAFT REPORT, SEPTEMBER 26, 2006
Some Key Recommendations
1. Planned Knowledge Assessments
Reappraisal required for all new drug entities 5 years after approval
2. New Tri-furcation of Authority
• Federal licensing unit FDA Center for Drug Evaluation and Research
• Strengthened and more credible outside committees of experts
• Enlarged and toughened FDA Office of Safety Evaluation
3. New Knowledge-Generation Program for pursuing clinical trials and
gathering data on existing drugs. This program would end FDA’s virtual
dependence on industry-designed studies.
A Prime Example of Planned Adaptation with Dual Capabilities
• To generate new data to reduce uncertainties of policy relevance
• To incorporate new data in improved policy, as a matter of routine
…………………………………………………………..IF adopted.
SUMMARY OF MAIN POINTS
The Issue: Protecting the public from adverse effects of already-approved drugs
How We Anticipate: We require expensive clinical trials prior to approval.
Pre-approval trials - expose hundreds of mostly healthy individuals for short periods
Post approval use - millions of exposures of less healthy people for long periods
How we Adapt:
Post-marketing surveillance program [PMS] at the FDA
Add-on “Phase 4” trials after formal approval
Is it Working?
FDA PMS program thought to catch under 2% of adverse effects [weak incentives]
~100,000 die of adverse effects in US hospitals each year
Big awkward failure cases: Vioxx, depressants and teen suicide, etc.
Only a fraction of Phase 4 studies done, and FDA unconcerned
Further Improvements?
De novo review studies each 5 years? [EU policy, US IOM proposal]
A new review authority outside FDA? [New England Journal of Medicine]
Pharmaceuticals
initial approval and aftermarket reappraisal
SOx and PM
late adaptation
BSE
TSE Roadmap
Iraq WMD
CFC – Ozone
Food Safety
CDC USDA and HAACP
Diet – Transfats
SULFUR DIOXIDE – LATE ADAPTATION
Portions of case from Kate Martin
Expected Costs of S02 Reduction
1990 $550 per ton ± $250
2005 $250 per ton ± $ 50
Expected Benefits of SO2 Reduction
1990: acid rain benefits
$20 Million
2005: acid rain benefits
$69 Million
+ massive health benefits
Quotas and Targets
New PM NAAQS need to be met by all.
Old SO2 NAAQS standard unchanged.
Clean Air Interstate Rule will reduce SO2 by 70% from 2003 levels by 2015. This is an
additional 67% cut in SO2 from 2010 levels of the Acid Rain Program.
Potential benefits of PM cuts recognized in 1990…..changes coming in now.
Source: Figure 2 from US EPA, Acid Rain Program 2004 Progress Report.
Six Cities Cohort Follow-up
1990 - 1998
M o rtality Risk Ratio
1.4
1.3
1.2
Kingston
1.1
Topeka
Portage
1.0
Steubenville
0.9
St. Louis
0.8
Watertown
0.7
0
5
10
15
20
PM 2.5 (μ g/m3)
25
30
3
Figure 3 & 6, US EPA, Acid Rain Program 2004 Progress Report.
Pharmaceuticals
SOx and PM
late adaptation
BSE
TSE Roadmap
Iraq WMD
CFC – Ozone
Food Safety
CDC USDA and HAACP
Diet – Transfats
BSE POLICY ISSUES
TESTING
SCREENING TEST (ELISA)
FOR WHAT PROPORTIONS OF DOWNER CATTLE?
FOR APPARENTLY HEALTHY CATTLE?
FOR CATTLE OF WHAT AGE?
VOLUNTARY TESTING ALLOWED?
CONFIRMATION TESTS IMMUNO HISTOCHEMISTRY?
CONFIRMATION TESTS WESTERN BLOT?
CONTROLS
CULLING INFECTED HERDS WITH COMPENSATION
USE OF ANIMAL PRODUCTS IN ANIMAL FEED – CNS? BONE? PLATE WASTE?
SPECIALIZED RISK MATERIALS AND BONE FOR HUMAN CONSUMPTION?
BANS BY AGE -- ALL CATTLE OVER 20 MONTHS? OVER 30 MONTHS?
IMPORT RESTRICTIONS
NOTE: PLACEHOLDER FOR SLIDE WITH COMPARATIVE TESTING RATES AND RESULTS
The BSE Inquiry was announced in Parliament on 22
December 1997, and set up on 12 January 1998, to
establish and review the history of the emergence and
identification of BSE and new variant CJD in the United
Kingdom, and of the action taken in response to it up to
20 March 1996; to reach conclusions on the adequacy of
that response, taking into account the state of knowledge
at the time; and to report on these matters to the Minister
of Agriculture, Fisheries and Food, the Secretary of State
for Health and the Secretaries of State for Scotland,
Wales and Northern Ireland.
At the heart of the BSE story lie questions of how to handle hazard - a known
hazard to cattle and an unknown hazard to humans. The Government took
measures to address both hazards. They were sensible measures, but they were
not always timely nor adequately implemented and enforced.
Initial UK Policies and Perceived Transmission Paths
Contaminated feed
Asymptomatic > 30 mo
Downers
Asymptomatic < 30 mos
Cull infected herds
Test downers for BSE
SRM
Partial animal
feed ban
Interspecies
Barrier
vCJD
Note: Only 2 BSE and few vCJD cases reported
Query: Are BSE and vCJD cases underreported?
The rigour with which policy measures were implemented for the protection of human
health was affected by the belief of many prior to early 1996 that BSE was not a potential
threat to human life.
The Government introduced measures to guard against the risk that BSE might be a
matter of life and death not merely for cattle but also for humans, but the possibility of a
risk to humans was not communicated to the public or to those whose job it was to
implement and enforce the precautionary measures.
The Government did not lie to the public about BSE. It believed that the risks posed by
BSE to humans were remote. The Government was preoccupied with preventing an
alarmist over-reaction to BSE because it believed that the risk was remote. It is now clear
that this campaign of reassurance was a mistake. When on 20 March 1996 the
Government announced that BSE had probably been transmitted to humans, the public
felt that they had been betrayed. Confidence in government pronouncements about risk
was a further casualty of BSE.
Links and Sources of Uncertainty for EU and UK/GER/FR Policies
Contaminated feed
Poultry waste
Spontaneous cases
Scrapie, CWD
Downers
Ban downers as food
Cull infected herd
UK over 30 mo rule
Ban SRM
Test risk cattle > 24 /mo
Test normal > 30
Develop more sensitive tests?
SRM
Meat
Bone
Milk
Full animal
feed ban
Poultry feed
Interspecies
Barrier
vCJD
Other diseases
TSE ROADMAP
CHART 1: EU BSE CASES FROM 2001 TO 2004
TSE ROADMAP
CHART 2: EU BSE CASES BY BIRTH COHERTS
TSE ROADMAP
CHART 3: MEAN AGE OF POSTIVE CASES
IN HEALTHY SLAUGHTERED ANIMALS IN EU
Links and Sources of Uncertainty for EU and UK/GER/FR Policies
Contaminated feed
Poultry waste
Spontaneous cases
Scrapie, CWD
Downers
UK over 30 mo rule
Ban downers as food
Ban SRM
Test risk cattle > 24 /mo
Test normal > 30
Develop more sensitive tests?
SRM
Meat
Bone
Milk
Full animal
feed ban
Poultry feed
Interspecies
Barrier
vCJD
Other diseases
US BSE Policies
Contaminated feed
Downers
Ban downers as food
Ban SRM > 30 mo
SRM
Meat
Bone
Milk
Partial feed
ban
Interspecies
Barrier
vCJD
US BSE Policies with Additional Sources of Uncertainty
Contaminated feed
Poultry waste
Spontaneous cases
Scrapie, CWD
Downers
Ban downers as food
Ban SRM > 30 mo
SRM
Meat
Bone
Milk
Partial feed
ban
Poultry feed
Interspecies
Barrier
vCJD
Other diseases
Links and Sources of Uncertainty with Japanese Policies
Contaminated feed
Poultry waste
Spontaneous cases
Scrapie, CWD
Downers
Ban downers as food
Ban SRM
Test >21 mo
Prefectures require
tests on ALL beef
SRM
Meat
Bone
fund 3 yrs
Milk
Full animal
feed ban
Poultry feed
Interspecies
Barrier
vCJD
Other diseases
EU / UK / GERMANY / JAPAN RECOGNIZE UNCERTAINTY OVER VALUE OF TESTING
FUND EXPERIMENTS TO ASSESS VALUE OF TESTS X EXPOSURE RECENCY X TISSUE
Incidence of
measured
abnormalities
in tissue
Central
Nervous
System
Gut
Lymph
0
3
6 9 12 15 18 21
Time in Months Since Exposure
24
27
30
33
36
39
12-03
01-04
10-04
06-05
10-05
11-05
12-05
01-06
02-06
07-06
CREEKSTONE ACTIONS AND RESULTS
US-JAPAN BSE BEEF TRADE CONFLICT
• BSE found in Washington cow
• Japanese consumers panic
• US beef becomes symbol of food risk
• Japan bars US beef; seeks BSE testing
of US beef as condition of access
• US rejects Japan position; insists that
Japan accept US beef without testing
• Koizumi offers access for untested US
beef < 20 months “in principle” . . .
IFF Japan Food Safety Commission OKs
• To regain access to Japan market, Creekstone
offers voluntary testing of beef slated for Japan.
• Large meat processors strongly oppose
mandatory and voluntary BSE testing.
• USDA bans Creekstone BSE testing, claiming
“no scientific basis” for testing healthy animals.
• USDA ban generates attention for Creekstone as
a firm willing to go the extra mile for safety.
• Creekstone picks up new domestic US orders.
• USDA Inspector General orders retest of
Texas cow; BSE found on retest.
• USDA revises feed and test rules
• Japan Food Safety Commission issues
qualified risk assessment on US beef
• Japan opens to US beef < 20 months
without specialized risk material (SRM)
• EU Ambassador visits Creekstone and praises
firm as exemplary US producer of hormone and
antibiotic free beef that will meet EU standards.
• Creekstone receives expedited EU certification
• Creekstone books strong Japan pre-orders as
customers favor Creekstone over generic beef
• Creekstone gets US & JPN cert; ships beef
• NY packer & USDA miss SRM JPN beef.
• Creekstone Japan exports vanish with closure
• Japan market re-closes to US beef
• JPN TV, Diet visit Creekstone & Tyson plants;
• Japan market re-opens to US beef
• Japanese criticize Tyson and praise Creekstone
• Distributor and consumer resistance
• Creekstone files against USDA on BSE test ban
Pharmaceuticals
SOx and PM
late adaptation
BSE
TSE Roadmap
Iraq WMD
CFC – Ozone
Food Safety
CDC USDA and HAACP
Diet – Transfats
HARVESTING INFORMATION TO UPDATE PRIORS -- IRAQ WMD
PRIORS
Iraq had chemical and biological weapons circa 1990
No UN inspections took place 1998-2002 hence limited info on Iraq WMD
Worst case assumptions on Iraq WMD were broadly shared
Bush-Chirac disagreed more over risks posed by WMD than over likelihood
Iraq wmd
If Underestimate => vulnerability to surprise attack and deterrence failure
If Overestimate => unnecessary arms spiraling and preemptive war
UN RESOLUTION AND INSPECTIONS AS AN UPDATING STRATEGY
IAEA inspections => Dramatic revision of priors re Iraq nuclear program
UNMOVIC inspections => Gradual revision of priors re chem bio and missiles
Information generated by UNMOVIC and IAEA undercut WMD justification for war
SINCERITY OF US INVOCATION OF PRECAUTION?
Bush issued ultimatum that forced out inspectors and ended updating of priors
2002
9.12
9.30
10.10
11.18
12.07
12.20
2003
1.12
1.27
2.05
2.10
2.19
3.01
3.17
3.20
BUSH SPEECH UN GENERAL ASSEMBLY ON NEW INSPECTIONS REGIME
IRAQ AGREES TO INSPECTIONS WITH OLD MODALITIES
BLIX TRAVELS TO BAGHDAD; MEETS ON LOGISTICS AND INSPECTIONS
IRAQ SUPPLIES BACKLOG OF SEMIANNUAL DECLARATIONS
UNSC 1441 “REQUIRES IRAQ TO COMPLY WITH ALL PREVIOUS RESOLUTIONS, LAST
CHANCE TO PROVE TO INTERNATIONAL COMMUNITY THAT IT HAD DISARMED”
IRAQ GIVES “LATEST CURRENTLY ACCURATE FULL COMPLETE DECLARATION
CAFCD” WITHOUT NAMES OF PEOPLE WHO HAD WORKED ON PREVIOUS PROGRAMS.
UNMOVIC FINDS “AIR FORCE DOCUMENT” ON CHEM WEAPONS USED IN IRAN WAR
RED LOGBOOK
BLIX: FINDS IRAQ OPEN TO INSPECTORS; SEEKS IRAQI ACTION TO PRESENT ITEMS
TO DESTROY AND CREDIBLE EVIDENCE ABOUT ABSENCE OFSUCH ITEMS.
EL BARADAI: “NO EVIDENCE THAT IRAQ HAS REVIVED ITS NUCLEAR WEAPONS
PROGRAMME,” INSPECTIONS “SHOULD BE ALLOWED TO RUN NATURAL COURSE.”
POWELL SPEECH TO UN SECURITY COUNCIL
INT’L PANEL OF MISSILE EXPERTS CONSIDER AL SAMOUD II AND AL FATAH
IRAQ INFORMS UNMOVIC OF UNILATERAL EXCAVATION OF OLD BIOWEAPONS
AL SAMOUD II DESTRUCTION
BUSH 48 HOUR ULTIMATUM TERMINATES INSPECTIONS
“..ALL FOREIGN NATIONALS, INCLUDING JOURNALISTS AND INSPECTORS,
SHOULD LEAVE IRAQ IMMEDIATELY.”
START OF SECOND GULF WAR
UN 1441 – AGREEMENT TO LEARN AND ADAPT
WHY DID THE PARTIES AGREE TO UN 1441 ?
US -- TO BUILD STRONGER CASE FOR WAR AT HOME AND ABROAD
CNN / USATODAY / GALLUP POLL FEBRUARY 2003
Would be convinced that war with Iraq was justified . . . .
If saw evidence that “Iraq has biological or chemical weapons”
85 %
If saw evidence that “Iraq is obstructing U.N. weapons inspectors” 76 %
PRIOR -- CBW WOULD BE FOUND AND/OR SADDAM WOULD OBSTRUCT
FRANCE -- TO POSTPONE OR AVOID WAR / TO UPDATE PRIORS
JOHN NEGROPONTE (United States)…. The resolution contained, he said,
no “hidden triggers” and no “automaticity” with the use of force.”
JEAN-DAVID LEVITTE (France) … France welcomed the lack of
“automaticity” in the final resolution.”
ZHANG YISHAN (China)…. The purpose was to disarm Iraq, and it no
longer contained any “automaticity” for the use of force. The Council must
meet again if there was non-compliance by Iraq.”
http://www.un.org/News/Press/docs/2002/SC7564.doc.htm
IRAQ DECLARATION
CHEM WEAPONS PRODUCED
UNMOVIC ACTIVITIES
OLD – interviews, documents
NEW – inspections, interviews, invoices
MINUS
CHEM WEAPONS EXPENDED
AGAINST IRAN AND KURDS
AIR FORCE DOCUMENT?
Captured 1980s document shows lower
than declared chemical use on Iran
MINUS
CHEM WEAPONS DESTROYED
VERIFICATION ?
Cannot confirm some disposal claims
EQUALS
CHEM WEAPONS UNACCOUNTED FOR
MONITORING AND INSPECTION,
Seek to locate or explain weapons
unaccounted for.
We have to date found no evidence that Iraq has revived its nuclear weapons
programme since the elimination of the programme in the 1990s. However, our
work is steadily progressing and should be allowed to run its natural course. With
our verification system now in place, barring exceptional circumstances, and
provided there is sustained proactive cooperation by Iraq, we should be able
within the next few months to provide credible assurance that Iraq has no nuclear
weapons programme.
Mohammed Baradai, January 27, 2003
2002
9.12
9.30
10.10
11.18
12.7
12.20
2003
1.12
1.27
2.05
2.10
2.19
3.1
3.17
3.20
RED LOGBOOK
TO DESTROY AND CREDIBLE EVIDENCE ABOUT ABSENCE OF SUCH ITEMS.
We also have satellite photos that indicate that banned materials
have recently been moved from a number of Iraqi weapons of
mass destruction facilities.
Let me say a word about satellite images before I show a couple.
The photos that I am about to show you are sometimes hard for
the average person to interpret, hard for me. The painstaking
work of photo analysis takes experts with years and years of
experience, pouring for hours and hours over light tables. But as I
show you these images, I will try to capture and explain what they
mean, what they indicate to our imagery specialists.
Let's look at one.
“Look at the image on the left. On the left is
a close-up of one of the four chemical
bunkers. The two arrows indicate the
presence of sure signs that the bunkers are
storing chemical munitions. The arrow at
the top that says security points to a facility
that is the signature item for this kind of
bunker. Inside that facility are special
guards and special equipment to monitor
any leakage that might come out of the
bunker. The truck you see is a signature
item. It's a decontamination vehicle in case
something goes wrong.
This is characteristic of those four
bunkers.”
“Now look at the picture on the
right. You are now looking at two of
those sanitized bunkers. The
signature vehicles are gone, the tents
are gone, it's been cleaned up, and it
was done on the 22nd of December,
as the U.N. inspection team is
arriving, and you can see the
inspection vehicles arriving in the
lower portion of the picture on the
right.
The bunkers are clean when the
inspectors get there. They found
nothing.”
2002
9.12
9.30
10.10
11.18
12.7
12.20
2003
1.12
1.27
2.05
2.10
2.19
3.1
3.17
3.20
RED LOGBOOK
TO DESTROY AND CREDIBLE EVIDENCE ABOUT ABSENCE OFSUCH ITEMS.
On November 8th, the Security Council unanimously passed Resolution
1441, finding Iraq in material breach of its obligations, and vowing serious
consequences if Iraq did not fully and immediately disarm. Today, no
nation can possibly claim that Iraq has disarmed. And it will not disarm so
long as Saddam Hussein holds power….. Saddam Hussein and his sons
must leave Iraq within 48 hours. Their refusal to do so will result in military
conflict, commenced at a time of our choosing. For their own safety, all
foreign nationals -- including journalists and inspectors -- should leave
Iraq immediately.
George W. Bush, March 17, 2003
Blix told reporters Tuesday that he never said Baghdad had weapons of mass
destruction, only a lot of unaccounted for material. He added that he did not think
Resolution 1441, adopted unanimously on Nov. 8, 2002, foresaw such a short
inspection time. "I don't think it is reasonable to close the door to inspections
after three and a half months," said Blix.
Hans Blix, March 17, 2003
Pharmaceuticals
new drug approval and aftermarket reappraisal
SOx and PM
late adaptation
BSE
TSE Roadmap
Iraq WMD
CFC – Ozone
Molina model, ozone hole, Dupont-ICI interest
Prospect of litigation and suppression of data
Food Safety
CDC USDA and HAACP
Diet – Transfats

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