.

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BK

London : Academic Press, an imprint of Elsevier, [2019]

xxii, 223 sran : ilustrace ; 23 cm

ISBN 978-0-12-818550-6 (brožováno)

Obsahuje bibliografii, bibliografické odkazy a rejstřík

001941827

List of figures xiii // List of tables xv // Preface xvii // Epigraph xix // List of abbreviations xxi // Part I The background, the debate, and the ethics involved // 1. Drug testing and pregnant women: background and significance 3 // Background of the issue 3 // Historical perspective 4 // Proponents of inclusion 5 // Significance of the issue 9 // Ethical concerns 11 // Aims of the book 12 // Notes 14 // 2. The rationales for and against inclusion 19 // Rationales against the inclusion of pregnant women in clinical research 21 // Rationale 1: the uncertain effect of new drugs on the mother and/or the fetus 21 // Rationale 2: litigation risk-because birth defects are not uncommon, they may occur unrelated to experimental drug exposure and result in spurious litigation 22 // Rationale 3: the number of pregnant women needed to participate in the study in order to show efficacy may be unachievable 23 // Rationale 4: safer study designs are available 24 // Rationale 5: alternative treatments are often available 25 // Rationale 6: little return on investment 25 // Rationale 7: regulations do not require inclusion 26 // Rationales for the inclusion of pregnant women in clinical trials 26 // Rationale 1: to acquire knowledge that improves the medical treatment of pregnant women and their offspring 26 // Rationale 2: to improve birth outcomes 27 // Rationale 3: to improve pregnant women’s access to the benefits of clinical research 28 //

Rationale 4: to improve the ethical acquisition of information about exposed pregnancies 29 // Rationale 5: regulations do not require the exclusion of pregnant women 30 // Rationale 6: excluding pregnant women from participating in medical research is unethical and illegal-and may increase litigation risk 30 // Rationale 7: to follow the advice of experts in the field of women’s health, law, and ethics 31 // Notes 32 // 3. The ethics involved 39 // Theoretical approaches 39 // Principle-based ethics 40 // The principle of respect for autonomy or respect for persons 40 // The principles of nonmaleficence, beneficence, and the double effect 41 // The principle of justice 42 // Consequentialism 43 // Feminist ethical theory 43 // Business ethics 46 // Special considerations for pregnancy/maternal-fetal ethics 48 // Application of an ethical framework for studies with pregnant women 50 // Notes 52 // Part II Quantitative and qualitative discoveries // 4. A measure of exclusion 59 // The US clinical trial system 59 // Are pregnant women excluded from US clinical trials? 61 // The measure of their exclusion 63 // Discussion 65 // Application of the findings 68 // Notes 69 // 5. Perspectives from the industry: on exclusion 71 // Groundwork 71 // Stakeholders on exclusion 72 // Question 1. Control 72 // Key findings for Question 1 75 // Question 2. Policy and practice 75 // Key findings for Question 2 77 // Question 3. Reasons for exclusion/barriers to inclusion 78 //

Key findings for Question 3 87 // Note 88 // 6. Perspectives from the industry: on inclusion 89 // Advocacy 89 // Question 4. Advocacy awareness 89 // Key findings for Question 4 90 // Stakeholders on inclusion 91 // Question 5. Inclusion 91 // Key findings to Question 5 95 // Question 6. Safeguarding safety 96 // Key findings for Question 6 97 // Alternative pathways 97 // Question 7. Other opportunities 97 // Key findings for Question 7 102 // Notes 103 // 7. Perspectives from the industry: on litigation, regulation, incentives, and indemnity 105 // Litigation 105 // Question 8: Litigation risk 105 // Key findings for Question 8 107 // Question 9: Litigation environment 107 // Key findings for Question 9 111 // External support 112 // Question 10: Regulatory agency support 112 // Question 11: Incentives 114 // Question 12: Indemnification 116 // Key findings for Questions 10, 11, and 12 117 // Notes 118 // 8. Perspectives from the industry: on ethics 119 // Research ethics 119 // Question 13. Ethical challenges 119 // Key findings for Question 13 126 // Notes 126 // Part III Uniting the regulators, the industry, and the advocates // 9. The FDA Guidance, public comment, and affinity with industry stakeholders 129 // Summary of US Food and Drug Administration guidance 129 // Kudos, comments, and criticisms to the draft guidance 131 // Notes 135 // 10. Proposed actions for FDA and the pharmaceutical industry 137 // Reconciling FDA guidance and industry perspectives 137 // FDA and industry stakeholders agree 137 // Perceived barriers and potential solutions 139 // Recommendations 140 // Proposals for pharmaceutical industry: actions to support the enrollment of pregnant women in clinical research 140 // Proposals for FDA: actions to support industry’s enrollment of pregnant women in clinical research 144 //

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 // Proposals for pregnant women’s advocacy groups: actions to support industry’s enrollment of pregnant women in clinical research 147 // Future steps 148 // Evaluation of the impact of the FDA guidance 148 // Benchmarking/best practices 150 // Additional recommendations in the stakeholders’ words 150 // Question 14: other solutions or incentives 150 // Notes 154 // 11. A chance at change 157 // Kingdon’s workstreams theory 157 // Advocates, policies, and politicians 158 // The problem stream 159 // Leadership in the problem stream 163 // The policy stream 164 // Leadership in the policy stream 165 // The political stream 166 // Leadership in the political stream 167 // Notes 169 // 12. After the guidance 173 // The pharmaceutical industry perspective 174 // The pregnant woman’s perspective 176 // Where are we now? 177 // Conclusion 180 // Notes 181 // Appendix I: FDA draft guidance-Pregnant women: scientific and ethical considerations for inclusion in clinical trials 183 // Appendix II: Executive summary: task force on research specific to pregnant women and lactating women 199 // Bibliography 207 // Index 219