Toward Earlier Inclusion of Pregnant and Postpartum Women in Tuberculosis Drug Trials: Consensus Statements From an International Expert Panel.

Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15-44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human immunodeficiency virus; (2) evaluating new agents/regimens for treatment of multidrug-resistant tuberculosis; and (3) evaluating safety, tolerability and pharmacokinetics of tuberculosis drugs already in use during pregnancy and postpartum. Incorporating pregnant women into clinical trials would extend evidence-based tuberculosis prevention and treatment standards to this special population.

[1]  S. Abdel‐Rahman,et al.  Special populations and pharmacogenetic issues in tuberculosis drug development and clinical research. , 2015, The Journal of infectious diseases.

[2]  K. Dooley,et al.  Pharmacokinetics of efavirenz and treatment of HIV-1 among pregnant women with and without tuberculosis coinfection. , 2015, The Journal of infectious diseases.

[3]  S. Swaminathan,et al.  Towards early inclusion of children in tuberculosis drugs trials: a consensus statement , 2015 .

[4]  K. Dooley,et al.  Designing drug trials: considerations for pregnant women. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  Alimuddin Zumla,et al.  The neglected global burden of tuberculosis in pregnancy. , 2014, The Lancet. Global health.

[6]  A. Moran,et al.  Tuberculosis in pregnancy: an estimate of the global burden of disease. , 2014, The Lancet. Global health.

[7]  A. Javed,et al.  Medicare readmission penalties in Detroit. , 2014, The New England journal of medicine.

[8]  R. Chaisson,et al.  Preventing Tuberculosis Among HIV-Infected Pregnant Women in Lesotho: The Case for Rolling Out Active Case Finding and Isoniazid Preventive Therapy , 2014, Journal of acquired immune deficiency syndromes.

[9]  D. Jamieson,et al.  Pregnancy and infection. , 2014, The New England journal of medicine.

[10]  D. Fitzgerald,et al.  Pregnancy Differentially Impacts Performance of Latent Tuberculosis Diagnostics in a High-Burden Setting , 2014, PloS one.

[11]  P. Zhao,et al.  Pharmacometrics in pregnancy: An unmet need. , 2014, Annual review of pharmacology and toxicology.

[12]  M. Boffito,et al.  Pharmacokinetic and Pharmacodynamic Drug Interactions Between Antiretrovirals and Oral Contraceptives , 2014, Clinical Pharmacokinetics.

[13]  Content and format of labeling for human prescription drug and biological products; requirements for pregnancy and lactation labeling. Final rule. , 2014, Federal register.

[14]  D. Jackson,et al.  Integration of tuberculosis and prevention of mother-to-child transmission of HIV programmes in South Africa. , 2013, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[15]  H. Coovadia,et al.  Integrating tuberculosis services into a PMTCT HIV programme in South Africa. , 2013, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[16]  P. Phillips-Howard,et al.  An Analysis of Pregnancy-Related Mortality in the KEMRI/CDC Health and Demographic Surveillance System in Western Kenya , 2013, PloS one.

[17]  O. Karabay,et al.  Should pyrazinamide be preferred in tuberculosis treatment during pregnancy? , 2013, The Indian journal of medical research.

[18]  Allan W. Taylor,et al.  Pregnancy Outcomes in HIV-Infected Women Receiving Long-Term Isoniazid Prophylaxis for Tuberculosis and Antiretroviral Therapy , 2013, Infectious diseases in obstetrics and gynecology.

[19]  Janine A Clayton,et al.  Enrolling pregnant women: issues in clinical research. , 2013, Women's health issues : official publication of the Jacobs Institute of Women's Health.

[20]  M. Kruijshaar,et al.  Risk of tuberculosis in pregnancy: a national, primary care-based cohort and self-controlled case series study. , 2012, American journal of respiratory and critical care medicine.

[21]  J. Stringer,et al.  Adherence to antiretroviral therapy during and after pregnancy in low-income, middle-income, and high-income countries: a systematic review and meta-analysis , 2012, AIDS.

[22]  N. Jana,et al.  Tuberculosis in pregnancy: The challenges for South Asian countries , 2012, The journal of obstetrics and gynaecology research.

[23]  Amita Gupta,et al.  Tuberculosis in pregnant and postpartum women: epidemiology, management, and research gaps. , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[24]  D. Matsui.  Adherence with Drug Therapy in Pregnancy , 2011, Obstetrics and gynecology international.

[25]  O. Loto,et al.  Tuberculosis in Pregnancy: A Review , 2011, Journal of pregnancy.

[26]  J. Hackman,et al.  Three months of rifapentine and isoniazid for latent tuberculosis infection. , 2011, The New England journal of medicine.

[27]  R. Chaisson,et al.  New regimens to prevent tuberculosis in adults with HIV infection. , 2011, The New England journal of medicine.

[28]  F. Chervenak,et al.  An Ethically Justified Framework for Clinical Investigation to Benefit Pregnant and Fetal Patients , 2011, The American journal of bioethics : AJOB.

[29]  A. Lyerly,et al.  Reframing the Framework: Toward Fair Inclusion of Pregnant Women as Participants in Research , 2011, The American journal of bioethics : AJOB.

[30]  Judith Mandelbaum-Schmid.  The global plan to stop TB 2011-2015 : transforming the fight towards elimination of tuberculosis , 2011 .

[31]  M. Hughes,et al.  Antiretroviral regimens in pregnancy and breast-feeding in Botswana. , 2010, The New England journal of medicine.

[32]  Michael G Hudgens,et al.  Maternal or infant antiretroviral drugs to reduce HIV-1 transmission. , 2010, The New England journal of medicine.

[33]  M. Hoelscher,et al.  Tuberculosis in association with HIV/AIDS emerges as a major nonobstetric cause of maternal mortality in Sub‐Saharan Africa , 2010, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[34]  Rebecca Kukla,et al.  Risk and the Pregnant Body , 2009, The Hastings Center report.

[35]  A. Lyerly,et al.  Pregnancy and Clinical Research , 2008, The Hastings Center report.

[36]  G. Anderson.  Pregnancy-Induced Changes in Pharmacokinetics , 2005, Clinical pharmacokinetics.

[37]  Reviewer Guidance Evaluating the Risks of Drug Exposure in Human Pregnancies , 2005 .

[38]  H. Coovadia,et al.  Perinatal tuberculosis and HIV-1: considerations for resource-limited settings. , 2004, The Lancet. Infectious diseases.

[39]  C. Connolly,et al.  Maternal mortality associated with tuberculosis–HIV-1 co-infection in Durban, South Africa , 2001, AIDS.

[40]  M. Frederiksen.  Physiologic changes in pregnancy and their effect on drug disposition. , 2001, Seminars in perinatology.

[41]  W. Jusko,et al.  Approaches to pharmacokinetic/ pharmacodynamic modeling during pregnancy. , 2001, Seminars in perinatology.

[42]  Alimuddin Zumla,et al.  A study of maternal mortality at the University Teaching Hospital, Lusaka, Zambia: the emergence of tuberculosis as a major non-obstetric cause of maternal death. , 1999, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[43]  L. Soto-Ramírez,et al.  [Treatment of tuberculosis]. , 1997, Gaceta medica de Mexico.

[44]  N. Kass,et al.  Harms of excluding Pregnant Women from Clinical Research: The Case of HIV-Infected Pregnant Women , 1996, Journal of Law, Medicine & Ethics.

[45]  A. Pernet,et al.  Comparison of organ-specific toxicity of temafloxacin in animals and humans. , 1991, The American journal of medicine.

[46]  Programmierbarer Thermoblock,et al.  From industry , 1991 .