Index
A
AAMC. See Association of American Medical Colleges
Abbreviated NDAs, 32
“Academic detailing,” 183
Academic research enterprise, 2, 5, 28, 146.
See also Professional societies
Accelerated approval, 165
Accountability, by the FDA, need for greater, 4
Accutane, 120
ACE inhibitors, 38
Adverse drug reactions
monitoring, 98
Adverse event (AE) reporting, 54, 167
background incidence of, 114
electronic submission of, 109
prevalence of, 113
recommendations concerning, 7, 114–115
substantial under-reporting, 55, 109
Adverse Event Reporting System (AERS), 53–56, 98, 157, 184
Advertising. See Direct-to-consumer advertising;
Pharmaceutical advertising
Advisory committees, 44–46, 179, 211
on communication with the public, 188
and the credibility of safety science, 131–142
recommendations concerning, 9–10, 12, 133–134, 188–189
timeline for planning meetings of, 45
Advocacy movements, 177
AE. See Adverse event reporting
AERS. See Adverse Event Reporting System
The agency. See Food and Drug Administration
Agency for Healthcare Research and Quality (AHRQ), 21, 25, 113, 180, 183, 212
AIDS treatment advocacy movement, 22, 75
ALLHAT. See Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
Alosetron (Lotronex), 59
Amlodipine, 115
Antidepressants, warnings added to labels on, 17, 50
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), 115
Appropriations
as source of FDA funding, 13, 19, 23, 118, 193, 196, 198
Approval process, 27
accelerated, 165
safety signal strengthening and testing, 110–115
speed of, 16
APPROVe trials, 55
Association of American Medical Colleges (AAMC), 142, 211
Automated healthcare databases, 7, 114–115
Azidothymidine (AZT), 37
B
Bain report, 32
Best Pharmaceuticals for Children Act, 57, 152, 165
“Best practices,” disseminating, 87–88
Bias, intellectual, 141
Biologics license application (BLA) submissions, 42
numbers of new approvals, 42
Biotechnology Industry Organization (BIO), 88
Bioterrorism and Preparedness and Response Act, 23
BLA. See Biologics license application submissions
Booz Allen Hamilton, 211
Boston Consulting Group, 123
British National Formulary, 170
Bromfenac, 38
Bureau of Labor Statistics, 92
Bush, President George W., 88, 207
C
C-Path Institute, 213
Calcium-channel blockers, 115
Cardiovascular risks, 112, 116
CBER. See Center for Biologics Evaluation and Research
CDC. See Centers for Disease Control and Prevention
CDER. See Center for Drug Evaluation and Research
CDRH. See Center for Devices and Radiological Health
Celecoxib, 17
Center for Biologics Evaluation and Research (CBER), 49, 129, 188
Center for Devices and Radiological Health (CDRH), 188
Center for Drug Evaluation and Research (CDER), ix–x, 15, 21, 31, 46–47, 49, 65, 105, 179, 193–202, 205.
See also Organizational dysfunction in the CDER culture;
Solutions proposed for CDER’s organizational dysfunction
credibility of, 85
history of funding, 194
IT needs within, 202
organizational culture in, 4, 66
press coverage of internal problems in, 2
recommendations concerning review teams, 10, 146–147
relevant changes at, 210
shepherding products through trials, 154
Center for Outcomes and Evidence, 212
Centers for Disease Control and Prevention (CDC), 81, 112, 128
Centers for Education and Research on Therapeutics (CERTs), 109
Centers for Medicare and Medicaid Services (CMS), 21, 25, 115, 180–181, 201
Central Hudson Gas & Electric Corp. v. Public Service Commission, 159–160
CERTs. See Centers for Education and Research on Therapeutics
CFR. See Code of Federal Regulations
Changes at the FDA
during course of study, 205–215
Critical Path Initiative and partnerships, 212–213
Drug Safety Initiatives, 205
Drug Safety Oversight Board, 205–206
Drug Watch Web page, 206
labeling, 210
leadership changes in the FDA, 207–208
other relevant changes at the FDA and CDER, 210
recent materials from the FDA, 208–209
structural changes and leadership changes in the CDER, 206–207
Changes in the broad context of drug regulation, 19–21
The charge (to the committee), 21–24
the shifting landscape of drug safety, 26
toward a new vision of drug safety, 26–28
Chlorthalidone, 115
Citizens’ Advisory Committee, 130
Clinical development, PDUFA goal for, 42
Clinical holds, 154
Clinical investigation (phase 2) studies, 35
Clinical pharmacology (phase 1) studies, 35
Clinical review templates, in postmarketing, 79–80
early, and related studies, 34–35
formal (phase 3), 35
in IND submission and review, and their limitations, 37–39
premarket, 38
recommendations regarding, 10, 144–145
Clozapine, 168
CMS. See Centers for Medicare and Medicaid Services
Code of Federal Regulations (CFR), 153, 159
COI. See Conflict of interest considerations
Commissioner of the FDA, 5–6, 9, 92–93, 131.
See also individual commissioners
instability in the office of, 5, 88–89
Committee on Identifying and Preventing Medication Errors, 24
Committee on Patient Education, 187
Committee on the Assessment of the US Drug Safety System, 2, 17, 65, 105, 178
Communication about safety, 27, 177–192
FDA’s challenges in, 4, 184–190
how industry communicates to the public and patients, 184, 188
between providers and the drug safety system, 181–184
between the public and the drug safety system, 178–179
recommendations concerning, 12–13, 188–189
roles and needs of providers and patients, 178–184
structure needed to support an effective drug safety system, 4
Confirmatory studies, 143n
reducing uncertainty about risk and benefit after approval, 115–119, 122
Conflict of interest (COI) considerations, 45, 86, 93, 134–142
appearance of, 73
“cover memos” regarding, 135–139
recommendations concerning, 141–142
zero-tolerance policy regarding, 140–141
Congress, 2, 4, 8, 48, 66, 69, 95, 97, 117–119, 153
ensuring that CDER receives needed authority and assets, x, 18
periodic reports to, 23, 71, 197, 202
recommendations to, 6–8, 11–13, 98–100, 117–119, 169–172, 197–203
Consumer Bill of Rights, 177
Consumer medication information, 185–187
criteria for useful, 187
Consumer Price Index, 23
Consumer Product Safety Commission, 114
Consumers.
See also AIDS treatment advocacy movement;
The public empowering, 20
representatives of, 179
Council of Public Representatives (COPR), 190
“Cover memos” regarding COI considerations, 135–139
CPI. See Critical Path Initiative
Crawford, Acting FDA Commissioner Lester M., 207
Credibility of safety science, 126–147
Critical Path Initiative (CPI), 33, 70n, 105, 201, 207, 211–213
report on, 20
Critical Path Opportunities Report, 212–213
Culture of safety in CDER, 27, 65–104
difficulties changing, 90
the external environment, 68–75
organizational challenges, 65–100
solutions proposed for CDER’s organizational dysfunction, 90–100
structural factors, policies, and procedures, 75–90
D
“DailyMed” health information clearinghouse, 210
Databases
automated, 56
DCLG. See Director’s Consumer Liaison Group
DDMAC. See Division of Drug Marketing and Communication
DDRE. See Division of Drug Risk Evaluation
“Dear Health Practitioner” letters, 58, 158
DEcIDE. See Developing Evidence to Inform Decisions about Effectiveness Network
Decision-making
concerning postmarket safety of a drug, ix, 47
political considerations in, 90
regulatory, by the FDA, ix
Department of Defense (DoD), 118
Department of Health and Human Services (DHHS), 2, 18, 41, 71, 74n, 93n, 113, 153, 180, 205.
See also Secretary of Health and Human Services
Department of Health, Education, and Welfare (DHEW), 74n
Department of Veterans Affairs (VA), 21, 92, 112–113, 201
academic, 183
Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) Network, 113, 180
Development cost, of drugs, 32
DHEW. See Department of Health, Education, and Welfare
DHHS. See Department of Health and Human Services
Dietary supplements, 153
Differing professional opinion (DPO) procedure, 47n
Direct-to-consumer (DTC) advertising, 21, 52–53, 158–164, 167, 171–172
court challenges to restricting, 159
deterrence of excessive, 198
need for more robust standards of assessment, 189
recommendations concerning, 11–12, 169–172
Director’s Consumer Liaison Group (DCLG), 190
Disagreement in the face of uncertainty, 127
nurturing a culture that values, 94
Discipline reviews, 79
different perspectives of, 86
Disclosure requirements, 141
Dispute resolution, 84
Division of Drug Marketing and Communication (DDMAC), 52, 78, 159, 163, 179
“DDMAC Watch,” 162
Division of Drug Risk Evaluation (DDRE), 32, 36, 51, 56
Division of Neurology Products (DNP), 36
DoD. See Department of Defense
DPO. See Differing professional opinion procedure
Drug approval process
limitations on, 59
Drug Development Science Obstacles and Opportunities for Collaborations, 211
Drug industry. See Pharmaceutical industry
Drug Price Competition and Patent Term Extension Act, 152
Drug Regulation Reform Act, 156
Drug safety
communication about, 27, 177–192
culture of safety in CDER, 27
experts in, 66
regulatory process and agency able to protect the public health, 27
rigorous science of, 27
the shifting landscape of, 26
warning the public about risks, 1
Drug safety activities, actionable performance goals for, 97
Drug Safety and Risk Management (DSaRM) Advisory Committee, 46, 87, 112, 133–134, 187
Drug Safety Initiative, 205
Drug Safety Management Board, 144
Drug Safety Oversight Board (DSB), 47, 82, 86–87, 99, 185, 187–188, 205–206
committee convened to assess, 2
communicating with providers, 181–184
communicating with the public, 178–179
communication structure needed to support effectively, 4
financial resources required to enable CDER to support the FDA mission, 4
impairment in, 4
organizational culture of CDER, 4
regulatory authority necessary to provide for drug safety, 4
regulatory science and processes necessary to enhance drug safety, 4
resources for, 4–5, 13–14, 166, 193–204
Drug Watch Web site, 57, 99, 179, 185, 187, 205–206
Drugs.
See also New drugs;
Prescription drugs;
Sponsors of drugs;
individual drugs cited
conditions linked to, 54
cost of, 178
development costs, 32
effectiveness of, 107
generics, 159
life-saving for specific patients, 1
“lifestyle,” 21
mechanisms of action, 2
milestones in lifecycle of, 167
over-the-counter, 90
pediatric, 165
potential benefit of, 34
promotion and information, postmarket, 52–53
promotion to patients greatly increased, 21
DSaRM. See Drug Safety and Risk Management Advisory Committee
DSB. See Drug Safety Oversight Board
DTC advertising. See Direct-to-consumer advertising
E
Economic impact of drugs, 32
Electronic medical records, 117
Electronic submission, of adverse event reports, 109
“End of phase 2 meeting,” in IND submission and review, 35–36
Enforcement tools, 163, 166–167
decisions about, 58
Enhancing Drug Safety and Innovation Act, 201n
Environmental Protection Agency, 197n
Epidemic Intelligence Service program, 128
Epidemiologic studies, 76, 86, 115, 201
Epidemiologists, safety teams of, 88
European Medicines Agency, 54, 158, 173, 211
Evaluation of FDA’s First Cycle Review Performance—Retrospective Analysis, 209
Exceptions, in FDA’s regulatory authority, 165
Expectations of multiple constituencies, conflicting, 69
Expertise
in the CDER, and the credibility of safety science, 127–131
in preapproval evaluation for the PDUFA IV, 98
External environment in CDER’s organizational dysfunction, 68–75, 97–100
the FDA-industry interface, 70–75
F
Fast track studies, 39
FDA. See Food and Drug Administration
FDA Science Board, 129
FDAMA. See Food and Drug Administration Modernization Act
FD&C. See Food, Drug, and Cosmetic Act
Federal Advisory Committee Act, 116, 146, 190
Federal advisory committees, on consumer issues, examples of, 190
Federal Aviation Administration, organizational problems at, 67, 91
Federal Communications Commission, 92, 197n
Federal Register, 45, 156, 161, 186
Federal Trade Commission (FTC), 160
Financial resources. See Resources for the drug safety system
First Amendment protections, of truthful commercial speech, 159, 161–162, 171, 183
Food and Drug Administration (FDA), ix–x, 1–12, 15, 23–25, 65, 105, 177, 180–181, 205.
See also Commissioner of the FDA;
Recent FDA materials
approval but not a lifetime guarantee, 2
challenges in communicating to the public and patients, 184–190
consumer medication information from, 185–187
credibility of, 4–5, 70, 85, 88, 132
filing and review of submitted marketing applications, PDUFA goal for, 43
history of drug regulation by, 152–153
history of DTC advertising regulation by, 160–161
improving communication with the public, 187–190
increasingly dependent on industry funding, 71
interface with industry, 70–75
need for greater accountability and transparency by, 4
need for increased resources, 151, 193
oversight and review of clinical trial protocols during development, PDUFA goal for, ix, 42
public confidence in eroded, 15
“regulatory capture” of, 73–74, 155, 196–197
regulatory decision-making by, ix
relevant changes at, 210
response to public meeting input, 185
Science Board, 129
Food and Drug Administration (FDA) authority, 51, 151.
See also Direct-to-consumer (DTC) advertising;
Strengthening FDA’s regulatory authority
to compel completion of postmarketing commitments, 155–157
exceptions in, 165
guidance documents, 41, 208–209
oversight of sponsor promotional activities, 158–164
recommendations concerning, 11, 170
to unilaterally impose risk-reducing remedies, such as label changes and distribution restrictions, 157–158
Food and Drug Administration Modernization Act (FDAMA), 143, 152, 156
Food, Drug, and Cosmetic (FD&C) Act, 16, 22–23, 48, 51, 69, 90, 152, 156, 159, 184
Food Research Laboratory, 129
FTC. See Federal Trade Commission
Funding. See Resources for the drug safety system;
User-fee funding system
G
Galson, CDER Director Steven, 207
GAO. See Government Accountability Office
Gates Foundation, 212
“General applicability” matters, 134n
General Practice Research Database (GPRD), 112, 200
Generic drugs, 159
Goals. See Performance goals
Government Accountability Office (GAO), 36, 57, 66, 71–72, 92, 158, 163
Government agencies
compared with private-sector counterparts, 68–69
GPRD. See General Practice Research Database
GRMP. See Guidance for Review Staff and Industry: Good Review Management Principles and Practices for PDUFA Products
compared to MAPPs, 77n
writing, 41
Guidance for Industry: Consumer-Directed Broadcast Advertisements, 161
Guidance for Industry: Development and Use of Risk Minimization Action Plans, 119, 208
Guidance for Industry: Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment, 208
Guidance for Industry: Investigators, and Reviewers Exploratory IND Studies, 208
Guidance for Industry: Premarketing Risk Assessment, 208
Guidance for Review Staff and Industry: Good Review Management Principles and Practices for PDUFA Products (GRMP), 78
Guidance on Conflict of Interest for Advisory Committee Members, Consultants and Experts, 134
H
Health, commodification of, 184n
Health care delivery system, 2, 5, 28, 69, 177
Healthcare databases, automated, 7, 114–115
Henney, FDA Commissioner Jane, 16, 89
Hinchey Amendment, 45
History of the Food and Drug Administration (FDA)
CDER funding, 194
CDER staffing, 195
DTC advertising regulation, 160–161
HIV/AIDS crisis, 22.
See also AIDS treatment advocacy movement
Human subjects, protecting, 33–34
Hypothesis-testing studies, 143
I
ICH. See International Conference on Harmonisation
IND. See Investigational New Drug submission and review process
Indications, re-examination for new, 167
The industry. See Pharmaceutical industry
Infliximab, 109
Information technology (IT).
See also Databases;
Medication information;
Reference information
needs within the CDER, 202
Innovation or Stagnation?—Challenge and Opportunity on the Critical Path to New Medical Products, 212
Instability at the top, and CDER’s organizational dysfunction, 88–90
Institute of Medicine (IOM), ix–x, 2–3, 21, 24, 50, 66–67, 178, 182
Committee on Identifying and Preventing Medication Errors, 24
workshops, 143
Institutional review boards (IRBs), 33
Integrated Promotional Services, 56
Intellectual bias, 141
Interdisciplinary tension, 76
International Conference on Harmonisation (ICH), 54, 145, 208
International Society of Pharmacoepidemiology (ISPE), 112, 128
Interoffice polarization, and CDER’s organizational dysfunction, 83–85
Investigational New Drug (IND) submission and review process, 25–26, 33–39
completion of clinical trials and their limitations, 37–39
early clinical trials and related studies, 34–35
“end of phase 2 meeting” and phase 3 trials, 35–36
pre-new drug application submission meeting, 33, 39
roles of the OND and the ODS/OSE premarket, 36–37
IOM. See Institute of Medicine
IRBs. See Institutional review boards
Isotretinoin, 50, 120, 167–168
ISPE. See International Society of Pharmacoepidemiology
IT. See Information technology
K
Kaiser Foundation Research Institute, 111–112
L
See also Off-label use;
Symbol needed to denote limited knowledge about new drugs
changes, 167
FDA authority to unilaterally impose changes, 157–158
negotiations, 50
recommendations concerning, 11–12, 169–172
relevant changes at the FDA and CDER, 210
Leadership
in solving CDER’s organizational dysfunction, 91–94
Letters
“Dear Health Practitioner,” 58, 158
sent to drug sponsors in NDAs, 51
Lifecycle approach
to drug safety, conditions and restrictions on distribution throughout, 96, 167–170
“Lifestyle” drugs, 21
Lotronex, 59
M
Management Advisory Board, appointing an external, 6, 93–94
Management issues in CDER’s organizational dysfunction, 79–90
performance goals for the PDUFA IV, 100
Management studies, 68, 89–90, 95
Manual of Administrative Policies and Procedures (MAPPs), 47n, 77, 95
Mechanisms of action.
See also New molecular entities
of drugs, 2
MedDRA. See Medical Dictionary for Regulatory Activities
Medical Dictionary for Regulatory Activities (MedDRA), 54, 57
Medical Officer Retention Subcommittee, 82
Medical records, move toward electronic, 117
Medicare Modernization Act, 113
Medication guide, 157.
See also MedGuides
Medication information, private-sector developers of, 186
Medicine Plus program, 181
Medicines and Health products Regulatory Agency (MHRA), 170
MedWatch reporting system, 53–54, 109–110, 184
MHRA. See Medicines and Health products Regulatory Agency
Murglitazar, 107
N
NAS. See National Academy of Sciences
Natalizumab, 168
National Academies Public Access Records Office, 26n
National Academy of Sciences (NAS), 92
National Aeronautics and Space Administration, organizational problems at, 67, 82
National Cancer Institute (NCI), 190
National Disease and Therapeutic Index, 56
National Electronic Injury Surveillance System–Cooperative Drug Adverse Event Surveillance System (NEISS–CADES), 114
National Health Service, 171
National Institute for Health and Clinical Excellence (UK), 125
National Institute of General Medical Sciences, 128
National Institutes of Health (NIH), 20–21, 55, 81, 92, 116, 118, 180, 190
National Library of Medicine (NLM), 143, 145, 180–181, 183
National Prescription Audit, 56
National Science Foundation (NSF), 92
Natural history of a drug, 31–64
economic impact of drugs, 32
IND submission and review, 33–39
NCI. See National Cancer Institute
NDAs. See New Drug Applications
Needs, of providers and patients, 178–184
Negotiations, about label wording, 50
NEISS–CADES. See National Electronic Injury Surveillance System–Cooperative Drug Adverse Event Surveillance System
New Drug Applications (NDAs), 22–23, 32, 39–51, 106.
See also Abbreviated NDAs;
Supplemental NDAs
assembly of review team and beginning of review, 41, 43–44, 77, 96
composition of review teams, 78, 83
key review meetings, 48
letters sent to sponsors, 51, 79
PDUFA timetables and performance goals triggered, 40
postapproval requirements and labeling, 49–51
review teams, 6, 41, 43–44, 77, 96
site inspections, 51
New drugs, 2, 38, 107–119, 165
New molecular entities (NMEs), 41–44, 98, 106, 166
numbers of priority and standard approvals, 42
recommendations concerning, 9, 12, 133–134, 173
New vision of drug safety, 26–28
NIH. See National Institutes of Health
NLM. See National Library of Medicine
NMEs. See New molecular entities
NSF. See National Science Foundation
O
ODS/OSE. See Office of Drug Safety/Office of Surveillance and Epidemiology
Off-label use, 122
Office of Drug Safety/Office of Surveillance and Epidemiology (ODS/OSE), 32, 48–57, 67, 75–78, 83–86, 129, 146, 207
role in IND submission and review, 36–39
staffing, 107
Office of Drug Safety Policy and Communication. See Office of Safety Policy and Communication
Office of Generic Drugs, 32
Office of the Inspector General (OIG), 71, 156
Office of Management and Budget, 18, 95
Office of New Drug Chemistry, 78
Office of New Drugs (OND), 32–36, 51, 56–57, 67, 75–79, 82–86, 105, 146, 194–195, 206–207
role in IND submission and review, 36–37
Office of Safety Policy and Communication, 13, 185, 187, 189, 207
OIG. See Office of the Inspector General
OND. See Office of New Drugs
Opinion differences and CDER’s organizational dysfunction, 85–87
Organizational dysfunction in the CDER culture, 4, 65–100.
See also Solutions proposed for CDER’s organizational dysfunction
instability and politicization, 88–90
internal disagreements about handling of safety issues, 47
interoffice polarization, 83–85
mass media coverage of, 66, 84
policies, and procedures in solving, 77–90
recommendations concerning, 5–7
scientific disagreement and differences of opinion, 85–87
suboptimal work environment, 81–83
Orphan Drug Act, 152
P
Package inserts, for patients, 185
Patient Health Advisories, 206
Patient package inserts, 185
access to drugs, 16
advocacy movements for, 177
more engaged and knowledgeable, 21
need to reassure, 147
PDUFA. See Prescription Drug User Fee Act
Pediatric drugs, 165
Peer-review, 118
recommendations concerning, 12, 173
Performance goals (suggested for) PDUFA IV, 98–100
in performance report to Congress, 98–100
Pharmaceutical advertising.
See also Direct-to-consumer advertising
tax deductibility of, 199
Pharmaceutical drugs. See Drugs
Pharmaceutical industry, 2, 146, 177.
See also Sponsors of drugs;
User-fee funding system
communications with the public and patients, 158, 184, 186
social responsibility of, 119
Pharmaceutical Research and Manufacturers of America (PhRMA), 89, 123, 143, 162–163, 196
guiding principles on DTC advertising, 164
Pharmacoepidemiology
need for career-development awards in, 128
recommendations concerning, 9, 134–141
Pharmacogenomics, 34
Pharmacovigilance, 208
Phases of clinical trials and medicine development, 35
phase 1–clinical pharmacology studies, 34–35, 37
phase 2–clinical investigation studies, 34–35, 37
phase 3–formal clinical trials, 35–36, 124
phase 4–postmarketing surveillance, including further formal therapeutic trials, 35, 55, 106, 111, 117, 133, 157, 211
Plan B (emergency contraceptive), 89–91
Planning advisory committee meetings, timeline for, 45
Polarization, interoffice, 66, 68, 80–85
Policies and procedures, and CDER’s organizational dysfunction, 77–79
Political considerations, in decision-making, 90–91
Politicization, and CDER’s organizational dysfunction, 88–90
Postmarketing safety of a drug, 51–59, 95–97
decision-making concerning, ix, 47
drug promotion and information, 52–53
identifying and evaluating spontaneous safety signals, 56–58
recommendations concerning, 8, 127–131
requirements and labeling, in NDAs, 25, 49–51
risk communication activities and risk management for the PDUFA IV, 99
spontaneous adverse event reporting system, 53–55
Postmarketing study commitments, 155, 172–173, 211
for the PDUFA IV, 99
Postmarketing surveillance, including further formal therapeutic trials (phase 4), 35
PPP. See Pregnancy Prevention Program;
Public-private partnership
Pre-new drug application submission meeting, 39
Preapproval period, 37, 123, 154–155
safety conferences during, 48
Predictive Safety Testing Consortium, 213
Pregnancy Prevention Program (PPP), 120
Premarket clinical trials, 38
Prescribers’ understanding, 5
Prescription Drug User Fee Act (PDUFA), 15, 66, 70–74, 116, 154–155, 193.
See also User-fee funding system
clinical development of, 42
deadlines in, 49
FDA filing and review of submitted marketing applications, 43
FDA oversight and review of clinical trial protocols during development, 42
in NDAs, 40
PDUFA II, 16, 23, 35–36, 40, 72–73
PDUFA III, 35–36, 40, 48–49, 73, 121
Reauthorization Performance Goals and Procedures, 23
sponsor-requested meetings with FDA during clinical development, 42–43
sunset of approaching, 19
timetables and performance goals triggered, 40
Prescription Drug User Fee Act (PDUFA): Adding Resources and Improving Performance in FDA Review of New Drug Applications, 209
Prescription drugs
off-label use, 122
providers’ knowledge about, 179
taking multiple, 153
Prescriptions, taxing, 198
Preventing Medication Errors, 50, 178, 182
Princeton Survey Research Associates, 162
Priority reviews, 133
of new molecular entities, 41
Product seizures, 58
Product submissions, reductions in, 133
Professional opinions. See Differing professional opinion procedure
Program reviews or evaluations, 211–212
advisory committees, 211
postmarketing study commitments, 211
Project managers, 34
Promotion of drugs to patients.
See also Direct-to-consumer advertising;
Pharmaceutical advertising
increases in, 21
Propulsid, 17
Protection of human subjects, 33
Providers, roles and needs of, 178–184
improving communication with, 187–190
perspectives on DTC advertising, 162
Public Employees for Environmental Responsibility, 86n
Public Health Advisories, 206
Public-private partnership (PPP), 8, 117–119, 201
Pure Food and Drug Act, ix, 19n, 22, 152, 184
Q
Quality-adjusted life years (QALYs), 125
R
Randomized controlled trials, 86
Rationale for strengthening drug regulation, 164–166
realistic regulatory action on safety needed, without the “last call” of approvals, 166
Reauthorization Performance Goals and Procedures (PDUFA), 23, 196–199
guidance documents, 41, 208–209
reports, 209
adverse event reporting, 7, 114–115
advisory committees, 9–10, 12, 133–142, 188–189
amending the FD&C Act, 5–6, 92–93
automated healthcare databases, 7, 114–115
better science and expertise, 7–10
CDER review teams, 10, 146–147
for the Commissioner of the FDA, 5–6, 9, 92–93, 131
communication about safety, 12–13, 188–189
conflicts of interest, 10, 141–142
external Management Advisory Board, 6, 93–94
new molecular entities, 9, 12, 133–134, 173
Office of Drug Safety Policy and Communication, 13, 189
pharmacoepidemiology, 9, 134–141
postmarketing safety of a drug, 8, 127–131
from Preventing Medication Errors, 180–183
for providers and patients, 182–183
public-private partnership, 8, 117–119
risk-benefit analyses, 8, 125–126
safety-related performance goals for the PDUFA IV, 6–7, 98–100
for the Secretary of DHHS, 6, 8, 93–94, 117–119
Reference information, access to comprehensive, 182
Regulatory activities for safety, 4, 31.
See also Enforcement tools
in the postmarket period, 58–59
realistic needed, without the “last call” of approvals, 166
recommendations concerning, 10–12
Regulatory authority necessary to provide for drug safety, 4, 27, 151–176.
See also Food and Drug Administration authority
an aging and inadequate statutory framework, 153–166
history of FDA drug regulation, 152–153
strengthening FDA’s regulatory authority, 167–173
“Regulatory briefings,” 46
“Regulatory capture” of the FDA, 73–74, 155, 196–197
Regulatory “tool kit,” 168, 213
Research. See Academic research enterprise
Resources for the drug safety system, 5, 166, 193–204
levels required to enable CDER to support the FDA mission, 4
recommendations concerning, 13–14, 197–203
Review elements for new drug approval
current, 52
meetings key in NDAs, 48
Review Panel on New Drug Regulation, 74, 155–156, 172
Review teams, 34
in NDAs, assembling, 41, 43–44
Risk-benefit analyses
for approval decisions, 106–107, 166
evolving throughout the drug’s lifecycle, 2, 4, 96, 121–126
recommendations concerning, 8, 125–126
Risk communication activities, 27
postmarket, 97
Risk management
postmarket, 97
recommendations concerning, 11, 169–170
Risk Minimization Action Plans (RiskMAPs), 119–121, 146, 167
developing and assessing, 57, 158
Roles, of providers and patients (in drug safety system), 5, 178–184
S
Safety data, gaps in, 37
Safety officers, 37
Safety-related performance goals for the PDUFA IV, 98–100
expertise in preapproval evaluation, 98
monitoring of adverse drug reactions and the AERS, 98
performance management, 100
postmarketing risk communication
activities and risk management, 99
postmarketing study commitments, 99
See also Spontaneous safety signals in the postmarket period
reducing uncertainty about and benefit after approval, 108–115
in strengthening and testing, 110–115
Safety teams, of epidemiologists, 88
Safety “tool kits,” 213
Science-based decision-making, 66, 129
Science of safety, 27, 105–150
benefits after approval, 107–119, 122
and recommendations concerning expertise, 7–10
reducing uncertainty about, 107–119, 122
rigor in, 27
risk-benefit analyses throughout the drug’s lifecycle, 121–126
risk minimization action plans, 119–121
understanding risk and benefit for approval decisions, 66, 106–107
Scientific advances, 28.
See also Academic research enterprise
increasing the numbers of targeted drugs, 20
Scientific disagreement, and CDER’s organizational dysfunction, 85–87
Scientific reviewers, 34
Secretary of Health and Human Services, 6, 45, 93–94, 97
Sector maps, 110
Signals. See Safety signals
Site inspections, 51
in NDAs, 51
SMART (System to Manage Accutane Related Teratogenicity), 120–121
Social Security Administration, 92
Solutions proposed for CDER’s organizational dysfunction, 90–100
“Special Government Employees,” 131, 211
Special symbol needed to denote limited knowledge about new drugs, 170–172.
See also Black triangle
Sponsors of drugs
letters sent to, 51
materials generated by, 52
meeting with FDA during clinical development, PDUFA goal for, 42–43
non-compliance by, 18
obligations of, 34
Spontaneous safety signals in the postmarket period
identifying and evaluating, 56–58
See also individual stakeholders
Statement of task. See The charge (to the committee)
Statutory framework (for drug regulation)
FDA authority after approval, 155–164
FDA authority preapproval, 154–155
rationale for strengthening, 164–166
Steering Committee for the Collaborative Development of a Long-Range Action Plan for the Provision of Useful Prescription Medicine Information, 186
Strengthening FDA’s regulatory authority, 167–173
conditions and restrictions on distribution throughout the drug lifecycle, 167–170
greater regulatory flexibility post approval, 166
periodic review of data on NMEs, 172–173
special symbol needed to denote limited knowledge about new drugs, 170–172
Structural changes in the CDER, 206–207
Structural factors in CDER’s organizational dysfunction, 75–77
Supplemental NDAs, 31
Supplements, dietary, 153
Surrogate endpoints, 107
Suspension of approval, 173
T
Taxing prescriptions, 198
“Team approach,” 76.
See also Review teams;
Safety teams
Terfenadine, 109
Terminology coding, 54
Thompson v. Western States Medical Center, 160
Throckmorton, CDER Deputy Director Douglas, 207
Timeline, for planning advisory committee meetings, 45
Toxicologic studies, 44
Transparency
and the credibility of safety science, 142–147
need for greater, 4–5, 124, 127
Tufts Center for the Study of Drug Development, 71
U
Uncertainty, disagreement in the face of, 127
Under-reporting of adverse events, substantial, 55, 109
Union of Concerned Scientists, 86n
University of Arizona, 213
US drug safety system.
See also Committee on the Assessment of the US Drug Safety System
impaired by, 4
a transformed, 4
Useful consumer medication information, criteria for, 187
User-fee funding system, 16, 23, 40, 70, 83, 196–197
V
VA. See Department of Veterans Affairs
Vaccine Safety Datalink (VSD), 112
Valdecoxib, 17
Vanderbilt University, 111
Veterans Health Administration, 92
Vioxx, 65
Virginia State Board of Pharmacy v. Virginia Citizens Consumer Council, Inc., 159
Vision. See New vision of drug safety
von Eschenbach, FDA Acting Commissioner Andrew, 86n
VSD. See Vaccine Safety Datalink
W
Wall Street Journal, 162
Warning the public about drug safety risks, 1.
See also Black box warnings;
Labeling
Washington Legal Foundation, 162
Web sites, 25, 140, 142–143, 159, 172, 179, 181, 187, 190, 210
WHI. See Women’s Health Initiative
WHO. See World Health Organization
Withdrawals, 1–2, 16, 165, 173
Women’s Health Initiative (WHI), 55, 115, 123–124, 181
World Health Organization (WHO), 143, 145, 212
Z
Zero-tolerance policy, regarding COI considerations, 140–141