Drug survival and reasons for discontinuation of the first biological disease modifying antirheumatic drugs in Thai patients with rheumatoid arthritis: Analysis from the Thai Rheumatic Disease Prior Authorization registry.

Int J Rheum Dis. 2018 Jan;21(1):170-178

Authors: Narongroeknawin P, Chevaisrakul P, Kasitanon N, Kitumnuaypong T, Mahakkanukrauh A, Siripaitoon B, Katchamart W, Thai Rheumatism Association

Abstract
AIM: To evaluate and compare the retention rate of biological disease-modifying antirheumatic drugs (bDMARDs) in real-life practice and identify risk factors related to remission and drug discontinuation in patients with rheumatoid arthritis (RA).
METHOD: A total of 256 patients fulfilling criteria for RA and starting bDMARD between December 2009 and October 2014 were selected from the Rheumatic Disease Prior Authorization registry. Baseline demographic and clinical data were recorded. The cumulative probability of bDMARD discontinuation over 5 years of follow-up and factors associated with RA remission and bDMARD withdrawal were analyzed.
RESULTS: Almost half (46%) of patients were initially treated with rituximab (RTX), with 33% treated with etanercept (ETN) and 21% with infliximab (IFX). Fewer than 10% were subsequently switched to a second bDMARD. The 1- and 5-year remission rates in patients continuing their first bDMARD were 7.2% and 21.5%, respectively. At 5 years, the drug survival rates for RTX, ETN and IFX were 50%, 25% and 22%, respectively. Multivariate analysis showed that RTX was significantly associated with highest drug survival. Relative to RTX, the hazard ratios for discontinuation of IFX and ETN were 2.60 (95% confidence interval [CI] 1.53-4.42) and 2.15 (95% CI 1.36-3.42), respectively. Thirty-nine percent of patients stopped treatments, due to inadequate response (42%), serious adverse events (22%), nonadherence (14%) or remission/low disease activity (13%).
CONCLUSION: Over 5 years, only one-third of patients continued using their first bDMARD. The leading cause of drug discontinuation was inadequate response.

PMID: 28737837 [PubMed - indexed for MEDLINE]

Safety and General Considerations for the Use of Antibodies in Infectious Diseases.

Adv Exp Med Biol. 2017;1053:265-294

Authors: Hey AS

Abstract
Monocolonal antibodies are valuable potential new tools for meeting unmet needs in treating infectious dieseases and to provide alternatives and supplements to antibiotics in these times of growing resistance. Especially when considering the ability to screen for antibodies reacting to very diverse target antigens and the ability to design and engineer them to work specifically to hit and overcome their strategies, like toxins and their hiding in specific cells to evade the immuneresponse and their special features enabling killing of the infectious agents and or the cells harbouring them. Antibodies are generally very safe and adverse effects of treatments with therapeutic antibodies are usually related to exaggeration of the intended pharmacology. In this chapter general safety considerations for the use of antibodies is reviewed and the general procedures for nonclinical testing to support their clinical development. Special considerations for anti-infective mAb treatments are provided including the special features that makes nonclinical safety programs for anti-infective mAbs much more simple and restricted. However at a cost since only limited information for clinical safety and modeling can be derived from such programs. Then strategies for optimally designing antibodies are discussed including the use of combination of antibodies. Finally ways to facilitate development of more than the currently only three approved mAb based treatments are discussed with a special focus on high costs and high price and how collaboration and new strategies for development in emerging markets can be a driver for this.

PMID: 29549644 [PubMed - indexed for MEDLINE]

The First Step to Integrating Adapted Common Terminology Criteria for Adverse Events for Children.

J Clin Oncol. 2016 06 20;34(18):2196-7

Authors: de Rojas T, Bautista FJ, Madero L, Moreno L

PMID: 27114600 [PubMed - indexed for MEDLINE]

The safety and tolerability of aripiprazole once-monthly as maintenance treatment for bipolar I disorder: A double-blind, placebo-controlled, randomized withdrawal study.

J Affect Disord. 2018 Jul 06;241:425-432

Authors: Calabrese JR, Sanchez R, Jin N, Amatniek J, Cox K, Johnson B, Perry PP, Hertel P, Such P, McQuade RD, Nyilas M, Carson WH

Abstract
BACKGROUND: Aripiprazole once-monthly 400 mg (AOM 400), an atypical long-acting injectable antipsychotic, has demonstrated efficacy and safety in maintenance treatment of bipolar I disorder (BP-I). We further assess safety and tolerability and characterize adverse events (AEs) across the duration of aripiprazole exposure.
METHODS: Patients with BP-I were stabilized on oral aripiprazole (2-8 weeks), AOM 400 (12-28 weeks), followed by 1:1 randomization of patients meeting stability criteria to a 52-week, double-blind, placebo-controlled withdrawal phase. Treatment-emergent AEs (TEAEs) were collected across study phases. AEs were counted in a phase if they were drug-related and continued from the baseline of that phase. A separate analysis on new-onset akathisia was conducted.
RESULTS: Among TEAEs occurring in ≥10% of patients during all study phases were akathisia (23.3%) and weight increased (10.6%). Median time to akathisia onset was 20 days after starting oral aripiprazole; median duration was 29 days for the first occurrence; 21/168 patients (12.5%) reporting akathisia experienced >1 episode. Episodes of new-onset akathisia decreased over time, with few events reported in the randomized phase. Weight gain was minimal with oral aripiprazole, generally starting within 3 months after the first AOM 400 injection, and appearing to plateau at 36 weeks. The mean weight gain within any study phase was ≤1.0 kg. Potentially clinically significant changes in metabolic parameters were uncommon.
LIMITATIONS: Patients on placebo had AOM 400 exposure before randomization.
CONCLUSION: These findings suggest that AEs with AOM 400 treatment were time-limited and support AOM 400 as a well-tolerated maintenance treatment of BP-I.

PMID: 30145513 [PubMed - as supplied by publisher]

Toward safer prescribing: evaluation of a prospective drug utilization review system on inappropriate prescriptions, prescribing patterns, and adverse drug events and related health expenditure in South Korea.

Public Health. 2018 Aug 23;163:128-136

Authors: Kim SJ, Han KT, Kang HG, Park EC

Abstract
OBJECTIVES: This study aimed to evaluate the effect of the prospective drug utilization review (DUR) system introduced in Korea in December 2010 as a real-time method to improve patient safety, in terms of changes in prescribing practices, adverse drug events (ADEs), and ADE-related healthcare expenditure, using non-steroidal anti-inflammatory drugs (NSAIDs) and their common ADEs as a guide.
STUDY DESIGN: We used an interrupted time-series study design using generalized estimating equations to evaluate changes in prescription rate and ADE-related healthcare expenditure. Cox regression analysis was used to evaluate the probability of NSAID-associated ADEs.
METHODS: A total of 154,585 outpatients with musculoskeletal or connective tissue disorders, without pre-existing gastric bleeding or ulcers were included in this study. The primary outcome was the level and trend change in prescription rate, drug-drug interactions, coprescribed gastro-protective drugs, and defined daily dose (DDD) of NSAIDs. The secondary outcome was the probability of ADEs and changes in ADE-related healthcare expenditure.
RESULTS: There was a significant trend change after introducing the DUR system in terms of drug-drug interactions (-3.6%) and coprescribed gastro-protective drugs (+0.6%). The mean DDD of NSAIDs increased by 0.2. The probability of ADEs decreased overall (-1.7%) and in the high-risk group (age ≥65 years; -9.6%); however, only the latter was significant. There was no significant trend or level change in ADE-related health expenditure.
CONCLUSIONS: The introduction of the DUR system was associated with more efficient prescribing, including a reduction in drug-drug interactions and an increase in the use of gastro-protective drugs. The system had a positive effect on patient outcome but was not associated with reduced ADE-related costs. Further studies are needed to evaluate the long-term effects of the DUR system in Korea.

PMID: 30145461 [PubMed - as supplied by publisher]

Suspected drug-induced liver injury associated with iguratimod: a case report and review of the literature.

BMC Gastroenterol. 2018 Aug 24;18(1):130

Authors: Li XL, Liu XC, Song YL, Hong RT, Shi H

Abstract
BACKGROUND: Iguratimod is a novel anti-rheumatic drug with the capability of anti-cytokines as report goes. It has been reported that iguratimod is effective and safe for rheumatoid arthritis and other rheumatisms. As side effects, iguratimod can cause gastrointestinal reactions, dizziness, headache and itchy.
CASE PRESENTATION: In this case report, a 60-year-old female patient was admitted with suspected drug-induced liver injury (DILI) caused by iguratimod. The causality assessment was done by the updated RUCAM, and the possibility of the case in our paper diagnosed as highly probable for the score was 9 points. Iguratimod was discontinued immediately, and methylprednisolone was used for acute liver injury and Sjogren's syndrome. The data showed the patient has improved gradually, and she was discharged on day 27. The true incidence of iguratimod-related hepatotoxicity and its pathogenic mechanism are largely unknown. It is difficult to recognize and diagnose DILI, and there is no standard for diagnosis of DILI. At the same time, the DILI is still lack of specific treatment.
CONCLUSIONS: Based on this rare case of severe liver injury, we recommend careful monitoring of liver function throughout iguratimod treatment for diseases.

PMID: 30143001 [PubMed - in process]

Drug-induced liver injury: a safety review.

Expert Opin Drug Saf. 2018 Aug;17(8):795-804

Authors: García-Cortés M, Ortega-Alonso A, Lucena MI, Andrade RJ, Spanish Group for the Study of Drug-Induced Liver Disease (Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos GEHAM).l

Abstract
INTRODUCTION: Idiosyncratic drug-induced liver injury (DILI) remains one of the most important causes of drug attrition both in the early phases of clinical drug development and in the postmarketing scenario. This is because, in spite of emerging data on genetic susceptibility variants associated to the risk of hepatotoxicity, the precise identification of the individual who will develop DILI when exposed to a given drug remains elusive. Areas covered: In this review, we have addressed recent progress made and initiatives taken in the field of DILI from a safety perspective through a comprehensive search of the literature. Expert opinion: Despite the substantial progress made over this century, new approaches using big data analysis to characterize the true incidence of DILI are needed and to categorize the drugs' hepatotoxic potential. Genetic studies have highlighted the role of the adaptive immune system yet the mechanisms leading adaptation versus progression remain to be elucidated. There is a compelling need for development and qualification of sensitive, specific, and affordable biomarkers in DILI to foster drug development, patient treatment stratification and, improvement of causality assessment methods. Gaining mechanistic insights in DILI is essential to uncover therapeutic targets and design prospective clinical trials with appropriate endpoints.

PMID: 30059261 [PubMed - indexed for MEDLINE]

A narrative review of problems with medicines use in people with dementia.

Expert Opin Drug Saf. 2018 Aug;17(8):825-836

Authors: Eshetie TC, Nguyen TA, Gillam MH, Kalisch Ellett LM

Abstract
INTRODUCTION: People with dementia may be particularly susceptible to medication-related problems for various reasons. They include progressive cognitive decline, high sensitivity to the effect of medications on cognition and memory, and increased likelihood of comorbidities. Areas covered: This paper aimed to review current literature on the frequency and the types of medication-related problems, and their contribution to hospital admission in people with dementia. Literature searches were conducted using key search terms of dementia and medication-related problems. Studies investigating any medication-related problems in people with dementia or cognitive impairment were included. Expert opinion: Previous research showed a high prevalence of medication-related problems in people with dementia. However, no single category of medication-related problems was reported consistently as the most frequent type across studies. The available studies also showed that medication-related hospitalization was common among people with dementia. These findings underline the need for effective medication management services to reduce the risk of these problems in people with dementia and cognitive impairment. Further work is required to characterize medication-related problems comprehensively in this vulnerable patient group across settings of care. Future research should take a holistic approach in the identification of medication-related problems.

PMID: 29993294 [PubMed - indexed for MEDLINE]

Evaluating Twitter as a complementary data source for pharmacovigilance.

Expert Opin Drug Saf. 2018 Aug;17(8):763-774

Authors: Lardon J, Bellet F, Aboukhamis R, Asfari H, Souvignet J, Jaulent MC, Beyens MN, Lillo-LeLouët A, Bousquet C

Abstract
BACKGROUND: Social media are currently considered as a potential complementary source of knowledge for drug safety surveillance. Our primary objective was to estimate the frequency of adverse drug reactions (ADRs) experienced by Twitter users. Our secondary objective was to determine whether tweets constitute a valuable and informative source of data for pharmacovigilance purposes, despite limitations on character number per tweet.
RESEARCH DESIGN AND METHODS: We selected a list of 33 drugs subject to careful monitoring due to safety concern in France and Europe, and extracted tweets using the streaming API from 30 September 2014 to 5 April 2015. Two pharmacovigilance centers classified these tweets manually as potential ADR case reports.
RESULTS: Among 10,534 tweets, 848 (8.05%) implied or mentioned an ADR without meeting the four FDA criteria required for reporting an ADR, and 289 (2.74%) tweets were classified as 'case reports.' Among them 20 (7.27%) tweets mentioned an unexpected ADR and 33 (11.42%) tweets mentioned a serious ADR.
CONCLUSIONS: With the use of dedicated tools, Twitter could become a complementary source of information for pharmacovigilance, despite a major limitation regarding causality assessment of ADRs in individual tweets, which may improve with the new limitation to 280 characters per tweet.

PMID: 29991282 [PubMed - indexed for MEDLINE]

Adverse drug reactions of non-opioid and opioid analgesics reported to Croatian national authority from 2007 to 2014.

Acta Med Acad. 2017 Nov;46(2):94-104

Authors: Sunara P, Krnic D, Puljak L

Abstract
OBJECTIVE: Adverse drug reactions (ADRs) are commonly observed in the health services because of system weaknesses and individual errors. Analgesics are widely used and it can be expected that with the increased use one can expect increased number of ADRs of analgesics. The aim of this study was to analyze ADRs of non-opioid and opioid analgesics reported to the Croatian Agency for Medicinal Products and Medical Devices (HALMED) from 2007 to 2014.
METHODS: HALMED provided data on generic drug name, year of the ADR report, type of report, institution, reporting person, patient's age, sex and ADR type.
RESULTS: In the analyzed period 796 ADRs of analgesics were reported, of which 367 (46%) were serious ADRs. Number of ADR reports was continuously increasing during the analyzed period. There were 20 analgesics that had ≥5 reports, making 597 (75%) of all ADR reports for analgesics. The most common adverse reaction reports of those 20 analgesics referred to individual drugs (n=16; 80%). Most of the ADR reports were filed by physicians (n=257; 43%), followed by pharmacists (n=252; 42%). Most side effects (n=572; 96%) were reported spontaneously through appropriate forms by patients or health professionals. ADRs were most commonly reported in women (n=352; 59%) and most of them have occurred in adults (n=354; 59%). The most common ADRs of opioid and non-opioid analgesics have been reported on the skin and mucous membranes. Most serious ADRs were result of action of opioid analgesics.
CONCLUSION: Number of ADR reports in Croatia is continuously increasing and a considerable number of them refers to serious ADRs. To keep better track of medications and ADRs it is necessary to educate and encourage health professionals and patients in reporting side effects.

PMID: 29338273 [PubMed - indexed for MEDLINE]

Systematic review and meta-analysis of reported adverse events of long-term intranasal oxytocin treatment for autism spectrum disorder.

Psychiatry Clin Neurosci. 2018 Mar;72(3):140-151

Authors: Cai Q, Feng L, Yap KZ

Abstract
Recent studies have suggested oxytocin as a possible drug to treat social deficits caused by autism spectrum disorder (ASD), but the safety of intranasal oxytocin in autistic patients has not been established. The aim of this review was to characterize the side-effect profile of long-term intranasal oxytocin in treatment of ASD compared to placebo. All randomized controlled trials of intranasal oxytocin in the treatment of ASD published before 1 January 2017 that reported safety data were identified from databases, including PubMed, Embase, Cochrane Library, and International Pharmaceutical Abstract. Relevant data from the selected studies were then extracted for meta-analysis to estimate the pooled risk ratio for the most common adverse events. Descriptive analysis of severe adverse events was also conducted. Of the 223 participants in the five included studies, 123 were given oxytocin and 100 were given placebos. Nasal discomfort (14.3%), tiredness (7.2%), irritability (9.0%), diarrhea (4.5%), and skin irritation (4.5%) were the most common adverse events. None of these common adverse events was statistically associated with treatment allocation according to meta-analysis using pooled data (all P-values > 0.1). Five severe adverse events were reported, namely aggression (one in placebo, two in oxytocin) and seizures (one in placebo, one in oxytocin). Results from this systematic review support intranasal oxytocin as well tolerated and safe for use in the ASD population. Larger clinical trials should be conducted to establish the efficacy of intranasal oxytocin as a treatment of ASD.

PMID: 29232031 [PubMed - indexed for MEDLINE]

Effect of hydroxychloroquine on treatment and recurrence of acute brucellosis: a single-blind, randomized clinical trial.

Int J Antimicrob Agents. 2018 Mar;51(3):365-369

Authors: Majzoobi MM, Hashemi SH, Mamani M, Keramat F, Poorolajal J, Ghasemi Basir HR

Abstract
Brucellosis is associated with a high recurrence rate and requires more than one course of standard treatment; therefore, more research is required to find more effective treatments that lead to prompt recovery, and reduce the relapse of disease. This single-blind, randomized study was designed to evaluate the effect of the standard treatment for brucellosis in combination with hydroxychloroquine. A total of 177 patients with acute brucellosis were randomly assigned to one of two treatment groups: doxycycline-streptomycin (DS) and doxycycline-streptomycin-hydroxychloroquine (DSH). Clinical symptoms and signs, serological tests, and side effects of therapy were compared between the two groups during the treatment course and at three and six months after the end of drug therapy. Of the 177 patients, with a mean age of 40.5 ± 16.9 years, 66.1% were males. The mean duration of clinical signs prior to admission was 43.4 ± 41.1 days. Appropriate clinical responses, relapse, treatment failure, and adverse drug reactions were seen in 98.9%, 1.2%, 0.0%, and 12.6% of patients, respectively, in the DSH group vs. 86.7%, 11.6%, 2.3%, and 19.8% of patients, respectively, in the DS group. There were significant differences in clinical response and relapse rates between the two groups. The addition of hydroxychloroquine to a doxycycline-streptomycin regimen appears to increase the efficacy of treatment, accelerate improvement of clinical symptoms, and significantly reduce the rate of relapse of brucellosis.

PMID: 28826825 [PubMed - indexed for MEDLINE]

The Comparative Safety of TNF Inhibitors in Ankylosing Spondylitis-a Meta-Analysis Update of 14 Randomized Controlled Trials.

Clin Rev Allergy Immunol. 2018 Apr;54(2):234-243

Authors: Hou LQ, Jiang GX, Chen YF, Yang XM, Meng L, Xue M, Liu XG, Chen XC, Li X

Abstract
TNF inhibitors have been used in ankylosing spondylitis (AS). The efficacy of TNF inhibitors was already evaluated by meta-analysis of randomized controlled trials (RCTs). However, the safety of TNF inhibitors is still unclear. Therefore, we aimed to evaluate and update the safety data from RCTs of TNF inhibitors in patients treated for AS. A systematic literature search was conducted from 1990 through May 31, 2016. All studies included were randomized, double-blind, controlled trials of patients with ankylosing spondylitis that evaluated adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab treatment. The overall serious adverse events, the risk of serious infection events, and the risk of malignancy and discontinuation rates were abstracted, and risk estimates were calculated by Peto odds ratios (ORs). Fourteen randomized controlled trials involving 2032 subjects receiving TNF inhibitors and 1030 subjects receiving placebo and/or traditional disease-modifying anti-rheumatic drugs (DMARDs) were included. The overall serious adverse events (OR, 1.34; 95% CI, 0.87-2.05), the risk of serious infection events (OR, 1.59; 95% CI, 0.63-4.01), the risk of malignancy (OR, 0.98; 95% CI, 0.25-3.85), and discontinuation due to adverse events (OR, 1.55; 95% CI, 0.95-2.54) in patients treated with TNF inhibitors as a group were not significantly different from those treated with placebo in the control group. TNF inhibitors were generally safe for treatment of ankylosing spondylitis. These data may help guide clinical comparative decision making in the management of AS.

PMID: 28717941 [PubMed - indexed for MEDLINE]

Trichomonas vaginalis Treated With Boric Acid in a Metronidazole Allergic Female.

Sex Transm Dis. 2017 02;44(2):120

Authors: Backus KV, Muzny CA, Beauchamps LS

PMID: 27984554 [PubMed - indexed for MEDLINE]

Activity profile of the cisplatin analogue PN149 in different tumor cell lines.

Biochem Pharmacol. 2018 Aug 20;:

Authors: Schoch S, Sen V, Gajewski S, Golubev V, Strauch B, Hartwig A, Köberle B

Abstract
The efficacy of the anticancer drug cisplatin is restricted by tumor cell resistance and occurrence of severe side effects. One strategy to overcome these limitations is the development of new, improved platinum drugs. Previous investigations showed that platinum(IV)-nitroxyl complexes are able to circumvent cisplatin resistance in bladder cancer cells. In the present study the mode of action of the platinum(IV)-nitroxyl complex PN149 was investigated in the bladder cancer cell line RT112 and the renal cell carcinoma cell line A498 on the molecular and cellular level. Gene expression analysis showed that PN149 induced genes related to DNA damage response (RRM2B, GADD45A), cell cycle regulation (CDKN1A, PLK3, PPM1D) as well as those coding for the pro-apoptotic factors PUMA and Noxa. These findings on the transcriptional level were confirmed on the functional level revealing that PN149 treatment increased levels of p53 and resulted in cell cycle arrest and drug-induced cytotoxicity via induction of apoptosis. Regarding the expression of oxidative-stress sensitive genes, PN149 induced FTH1, GCLC, HMOX1 and TXNRD1 but relevant effects were restricted to RT112 cells treated with 50 µM. The pro-inflammatory IL-8 was induced by PN149 in RT112 but not A498 cells indicating a cell-type specific activation. Taken together, PN149 possessed promising activity in different tumor cell lines rendering it an interesting alternative to cisplatin in chemotherapy.

PMID: 30138622 [PubMed - as supplied by publisher]

Treatment with montelukast and antidepressive medication-a symmetry analysis.

Pharmacoepidemiol Drug Saf. 2018 Aug 23;:

Authors: Winkel JS, Damkier P, Hallas J, Henriksen DP

Abstract
PURPOSE: Leukotriene receptor antagonists are used in asthma and rhinitis treatment. Pharmacovigilance data have suggested an association between montelukast and depression, but the association has not been established in controlled study designs. We described the association between initiation of montelukast and depression, using prescriptions of antidepressants as a surrogate marker, and assessed whether the association was related to the underlying asthma disease.
METHODS: We performed a symmetry analysis, with a study period from January 1, 2000 to December 31, 2016, using 3 nationwide Danish registers. We included all adults, who filled their first prescription of montelukast and antidepressants within an interval of 1 year. In the absence of an association between montelukast and antidepressant use, a symmetrical distribution of prescriptions is expected before and after montelukast initiation (ie, a sequence ratio [rc ] of 1.0). We subcategorized the subjects after the severity of underlying asthma disease.
RESULTS: In total, 4450 subjects filled their first prescriptions of both montelukast and antidepressants within a 1-year interval: 2434 redeemed their first prescription of montelukast before antidepressants, and 2016 redeemed the medications in the opposite order (rc 1.21 [95% CI 1.14-1.28]). We found rc above unity in groups with long-acting asthma treatment, but no increase in antidepressant prescription, when stratifying by the asthma severity.
CONCLUSION: We found a weak association between the use of montelukast and the risk of being prescribed an antidepressant, unlikely to be of clinical relevance. Stratified analyses suggest that this association may relate to asthma, rather than to montelukast.

PMID: 30136330 [PubMed - as supplied by publisher]

Pregnancy and the global disease burden.

Reprod Health. 2017 Dec 14;14(Suppl 3):170

Authors: Sina BJ

Abstract
Pregnant women experience unique physiological changes pertinent to the effective prevention and treatment of common diseases that affect their health and the health of their developing fetuses. In this paper, the impact of major communicable (HIV/AIDS, tuberculosis, malaria, helminth infections, emerging epidemic viral infections) as well as non-communicable conditions (mental illness, substance abuse, gestational diabetes, eclampsia) on pregnancy is discussed. The current state of research involving pregnant women in these areas is also described, highlighting important knowledge gaps for the management of key illnesses that impact pregnancy globally.

PMID: 29297407 [PubMed - indexed for MEDLINE]

Research with pregnant women: a call to action.

Reprod Health. 2017 Dec 14;14(Suppl 3):156

Authors: Little MO, Wickremsinhe MN

Abstract
Despite a global need for the use of medication during pregnancy, the medical research community lacks robust evidence for safety and efficacy of treatments and preventives often taken by pregnant women. Given the biological differences between pregnant women and the rest of the population, the need to gather data on the ways in which medications behave in the pregnant body is critical to the health of pregnant women and their offspring. Three ethical reasons are central to this need: 1. Pregnant women deserve access to effective treatment, 2. Pregnant women deserve access to safe treatment, and 3. Pregnant women deserve equitable access to trials carrying the prospect of direct benefit. In this paper, we introduce and frame this Supplement Issue, which presents important conference proceedings of the 2016 Global Forum on Bioethics in Research meeting held in Buenos Aires, Argentina, on the 3rd and 4th of November.

PMID: 29297373 [PubMed - indexed for MEDLINE]

The global forum on bioethics in research meeting, "ethics of research in pregnancy": emerging consensus themes and outputs.

Reprod Health. 2017 Dec 14;14(Suppl 3):158

Authors: Hunt A, Banner N, Littler K

Abstract
Research during pregnancy is affected by multiple ethical challenges which have not received sufficient international attention and consideration from the bioethics, clinical, and policymaking communities working together. Unresolved ethical questions about research in pregnancy have significant detrimental impacts on maternal and newborn health, in part because they inhibit an evidence base being developed on the efficacy and safety of medicines and health interventions for pregnant women. These problems are compounded in low- and middle-income country (LMIC) settings due to variability in regulatory provisions, the burden of maternal morbidity and mortality, and many social and cultural conventions that impact on pregnant women's ability to participate in research. Research in pregnancy was chosen as a topic for the 2016 Global Forum on Bioethics in Research (GFBR) meeting, and its timeliness was all the more apparent given the 2016 Zika outbreak, which has deeply affected the Latin American region. The meeting's emerging consensus themes and outputs epitomized the core aims of the GFBR-to give voice to LMIC perspectives as a priority in dialogue about global health research ethics and to promote collaboration. In this instance, the GFBR meeting catalyzed a strong, unified drive to push researchers and policymakers to include pregnant women in research by default: given the complex nature of the topic, this is a significant achievement in addressing an important question of social justice.

PMID: 29297364 [PubMed - indexed for MEDLINE]

Ethics, regulation, and beyond: the landscape of research with pregnant women.

Reprod Health. 2017 Dec 14;14(Suppl 3):173

Authors: Saenz C, Cheah PY, van der Graaf R, Henry LM, Mastroianni AC

Abstract
Scarce research with pregnant women has led to a dearth of evidence to guide medical decisions about safe and effective treatment and preventive interventions for pregnant women and their potential offspring. In this paper, we highlight three aspects of the landscape in which pregnant women are included or, more frequently, excluded from research: international ethics guidance, regional and national regulatory frameworks, and prevailing practices. Our paper suggests that, in some cases, regulatory frameworks can be more restrictive than international ethics guidance, and that even when regulations permit research with pregnant women, practical challenges-as well as the prevailing practices of stakeholders, such as ethics review committees and investigators-may lead to the generalized exclusion of pregnant women from research.

PMID: 29297343 [PubMed - indexed for MEDLINE]