|
|
|
xiii | |
|
|
|
xv | |
| Preface |
|
xvii | |
| Epigraph |
|
xix | |
|
|
|
xxi | |
|
Part I The background, the debate, and the ethics involved |
|
|
|
1 Drug testing and pregnant women: background and significance |
|
|
3 | (16) |
|
|
|
3 | (1) |
|
|
|
4 | (1) |
|
|
|
5 | (4) |
|
Significance of the issue |
|
|
9 | (2) |
|
|
|
11 | (1) |
|
|
|
12 | (2) |
|
|
|
14 | (5) |
|
2 The rationales for and against inclusion |
|
|
19 | (20) |
|
Rationales against the inclusion of pregnant women in clinical research |
|
|
21 | (1) |
|
Rationale 1 The uncertain effect of new drugs on the mother and/or the fetus |
|
|
21 | (1) |
|
Rationale 2 Litigation risk---because birth defects are not uncommon, they may occur unrelated to experimental drug exposure and result in spurious litigation |
|
|
22 | (1) |
|
Rationale 3 The number of pregnant women needed to participate in the study in order to show efficacy may be unachievable |
|
|
23 | (1) |
|
Rationale 4 Safer study designs are available |
|
|
24 | (1) |
|
Rationale 5 Alternative treatments are often available |
|
|
25 | (1) |
|
Rationale 6 Little return on investment |
|
|
25 | (1) |
|
Rationale 7 Regulations do not require inclusion |
|
|
26 | (1) |
|
Rationales for the inclusion of pregnant women in clinical trials |
|
|
26 | (1) |
|
Rationale 1 To acquire knowledge that improves the medical treatment of pregnant women and their offspring |
|
|
26 | (1) |
|
Rationale 2 To improve birth outcomes |
|
|
27 | (1) |
|
Rationale 3 To improve pregnant women's access to the benefits of clinical research |
|
|
28 | (1) |
|
Rationale 4 To improve the ethical acquisition of information about exposed pregnancies |
|
|
29 | (1) |
|
Rationale 5 Regulations do not require the exclusion of pregnant women |
|
|
30 | (1) |
|
Rationale 6 Excluding pregnant women from participating in medical research is unethical and illegal---and may increase litigation risk |
|
|
30 | (1) |
|
Rationale 7 To follow the advice of experts in the field of women's health, law, and ethics |
|
|
31 | (1) |
|
|
|
32 | (7) |
|
|
|
39 | (20) |
|
|
|
39 | (1) |
|
|
|
40 | (1) |
|
The principle of respect for autonomy or respect for persons |
|
|
40 | (1) |
|
The principles of nonmaleficence, beneficence, and the double effect |
|
|
41 | (1) |
|
|
|
42 | (1) |
|
|
|
43 | (1) |
|
|
|
43 | (3) |
|
|
|
46 | (2) |
|
Special considerations for pregnancy/maternal-fetal ethics |
|
|
48 | (2) |
|
Application of an ethical framework for studies with pregnant women |
|
|
50 | (2) |
|
|
|
52 | (7) |
|
Part II Quantitative and qualitative discoveries |
|
|
|
|
|
59 | (12) |
|
The US clinical trial system |
|
|
59 | (2) |
|
Are pregnant women excluded from US clinical trials? |
|
|
61 | (2) |
|
The measure of their exclusion |
|
|
63 | (2) |
|
|
|
65 | (3) |
|
Application of the findings |
|
|
68 | (1) |
|
|
|
69 | (2) |
|
5 Perspectives from the industry: on exclusion |
|
|
71 | (18) |
|
|
|
71 | (1) |
|
Stakeholders on exclusion |
|
|
72 | (1) |
|
|
|
72 | (3) |
|
Key findings for Question 1 |
|
|
75 | (1) |
|
Question 2 Policy and practice |
|
|
75 | (2) |
|
Key findings for Question 2 |
|
|
77 | (1) |
|
Question 3 Reasons for exclusion/barriers to inclusion |
|
|
78 | (9) |
|
Key findings for Question 3 |
|
|
87 | (1) |
|
|
|
88 | (1) |
|
6 Perspectives from the industry: on inclusion |
|
|
89 | (16) |
|
|
|
89 | (1) |
|
Question 4 Advocacy awareness |
|
|
89 | (1) |
|
Key findings for Question 4 |
|
|
90 | (1) |
|
Stakeholders on inclusion |
|
|
91 | (1) |
|
|
|
91 | (4) |
|
Key findings to Question 5 |
|
|
95 | (1) |
|
Question 6 Safeguarding safety |
|
|
96 | (1) |
|
Key findings for Question 6 |
|
|
97 | (1) |
|
|
|
97 | (1) |
|
Question 7 Other opportunities |
|
|
97 | (5) |
|
Key findings for Question 7 |
|
|
102 | (1) |
|
|
|
103 | (2) |
|
7 Perspectives from the industry: on litigation, regulation, incentives, and indemnity |
|
|
105 | (14) |
|
|
|
105 | (1) |
|
Question 8 Litigation risk |
|
|
105 | (2) |
|
Key findings for Question 8 |
|
|
107 | (1) |
|
Question 9 Litigation environment |
|
|
107 | (4) |
|
Key findings for Question 9 |
|
|
111 | (1) |
|
|
|
112 | (1) |
|
Question 10 Regulatory agency support |
|
|
112 | (2) |
|
|
|
114 | (2) |
|
Question 12 Indemnification |
|
|
116 | (1) |
|
Key findings for Questions 10, 11, and 12 |
|
|
117 | (1) |
|
|
|
118 | (1) |
|
8 Perspectives from the industry: on ethics |
|
|
119 | (10) |
|
|
|
119 | (1) |
|
Question 13 Ethical challenges |
|
|
119 | (7) |
|
Key findings for Question 13 |
|
|
126 | (1) |
|
|
|
126 | (3) |
|
Part III Uniting the regulators, the industry, and the advocates |
|
|
|
9 The FDA Guidance, public comment, and affinity with industry stakeholders |
|
|
129 | (8) |
|
Summary of US Food and Drug Administration guidance |
|
|
129 | (2) |
|
Kudos, comments, and criticisms to the draft guidance |
|
|
131 | (4) |
|
|
|
135 | (2) |
|
10 Proposed actions for FDA and the pharmaceutical industry |
|
|
137 | (20) |
|
Reconciling FDA guidance and industry perspectives |
|
|
137 | (1) |
|
FDA and industry stakeholders agree |
|
|
137 | (2) |
|
Perceived barriers and potential solutions |
|
|
139 | (1) |
|
|
|
140 | (1) |
|
Proposals for pharmaceutical industry: actions to support the enrollment of pregnant women in clinical research |
|
|
140 | (4) |
|
Proposals for FDA: actions to support industry's enrollment of pregnant women in clinical research |
|
|
144 | (2) |
|
Proposals for Pharmaceutical Research and Manufacturers' Association (PhRMA) and Biotechnology Innovation Organization (BIO): actions to support industry's enrollment of pregnant women in clinical research |
|
|
146 | (1) |
|
Proposals for pregnant women's advocacy groups: actions to support industry's enrollment of pregnant women in clinical research |
|
|
147 | (1) |
|
|
|
148 | (1) |
|
Evaluation of the impact of the FDA guidance |
|
|
148 | (2) |
|
Benchmarking/best practices |
|
|
150 | (1) |
|
Additional recommendations in the stakeholders' words |
|
|
150 | (1) |
|
Question 14 Other solutions or incentives |
|
|
150 | (4) |
|
|
|
154 | (3) |
|
|
|
157 | (16) |
|
Kingdon's workstreams theory |
|
|
157 | (1) |
|
Advocates, policies, and politicians |
|
|
158 | (1) |
|
|
|
159 | (4) |
|
Leadership in the problem stream |
|
|
163 | (1) |
|
|
|
164 | (1) |
|
Leadership in the policy stream |
|
|
165 | (1) |
|
|
|
166 | (1) |
|
Leadership in the political stream |
|
|
167 | (2) |
|
|
|
169 | (4) |
|
|
|
173 | (10) |
|
The pharmaceutical industry perspective |
|
|
174 | (2) |
|
The pregnant woman's perspective |
|
|
176 | (1) |
|
|
|
177 | (3) |
|
|
|
180 | (1) |
|
|
|
181 | (2) |
| Appendix I FDA draft guidance---Pregnant women: scientific and ethical considerations for inclusion in clinical trials |
|
183 | (16) |
| Appendix II Executive summary: task force on research specific to pregnant women and lactating women |
|
199 | (8) |
| Bibliography |
|
207 | (12) |
| Index |
|
219 | |
Biežāk uzdotie jautājumi par e-grāmatām