Inclusion of pregnant and breastfeeding women in nonobstetrical randomized controlled trials.

BACKGROUND: There is an urgent need to prioritize and expedite the inclusion of pregnant and breastfeeding women in research. Characterizing trials that have successfully included these populations could inform the design and execution of future studies. In addition, up-to-date data on their inclusion in clinical research could assist in setting benchmarks, establishing targets, and monitoring progress toward more equitable inclusion. OBJECTIVE: This study aimed to characterize the eligibility and enrollment of pregnant and breastfeeding women in randomized controlled trials evaluating interventions for nonobstetrical conditions experienced by, but not limited to, these populations. STUDY DESIGN: We developed a literature search in collaboration with an information specialist. We included randomized controlled trials published between 2017 and 2019 in the 5 highest-impact general medicine journals and the 3 highest-impact specialty journals in cardiovascular disease, critical care, general infectious diseases, HIV, and psychiatry. We included randomized controlled trials that evaluated screening, diagnosis, prevention, or treatment of nonobstetrical medical conditions. We excluded randomized controlled trials exclusively focused on males, pediatrics, geriatrics, oncology, or postmenopausal women, and publications reporting subgroup, pooled, or follow-up analyses of previously published randomized controlled trials. We screened titles and abstracts independently and in duplicate, with discrepancies resolved by a third reviewer. We entered data into a standardized electronic case report form. We reviewed study protocols, appendices, and trial registries for additional data. RESULTS: Of the 1333 randomized controlled trials, pregnant and breastfeeding women were eligible for 13 (1.0%) and 6 (0.5%), respectively. Pregnancy and breastfeeding eligibility criteria were not addressed in 383 of 1333 (28.7%) and 710 of 1333 (53.3%) randomized controlled trials, respectively. In total, 102 of 937 (10.9%) and 33 of 617 (5.3%) randomized controlled trials that explicitly excluded pregnant and breastfeeding women documented the rationale. Most studies excluding pregnant women (542/937; 57.8%) required at least 1 method of contraception and/or pregnancy testing as part of trial participation for women with reproductive capacity. Among the 13 randomized controlled trials that allowed inclusion of pregnant women, 3 restricted eligibility to specific trimesters. Two randomized controlled trials enrolled pregnant women after the first year of the study following interim review of safety results in nonpregnant participants. Four randomized controlled trials reported the number of pregnant women enrolled, which ranged from 0.7% to 3.4% of the study population. None of the studies reported on pregnancy or perinatal outcomes. Compared with randomized controlled trials that excluded pregnant women, those including them more commonly had an infectious disease focus (12/13 [92.3%] vs 270/937 [28.8%]; p<.0001), including HIV (5/13 [38.5%] vs 96/937 [10.2%]; p=.0079), enrolled participants in sub-Saharan Africa (5/13 [38.5%] vs 111/937 [11.8%]; p=.0143), and had exclusively nonindustry sponsorship (13/13 [100%] vs 559/937 [59.7%]; p=.0025); inclusion varied by study phase, randomization level, and intervention type. CONCLUSION: This study illustrates a major inequity in research involving pregnant and breastfeeding women. As new health challenges arise, including novel pandemics, and the research community mobilizes to develop therapies and innovate in patient care, it is crucial that pregnant and breastfeeding women not be left behind. Greater regulatory support, in the form of explicit requirements and incentives, will be needed to ensure these populations are integrated into the research agenda.

The quality of cardiac rehabilitation in Canada: a report of the Canadian Cardiac Rehab Registry.

Cardiac rehabilitation (CR) significantly reduces morbidity and mortality compared with usual care. CR quality indicators (QIs) have recently been established in Canada. This article presents an assessment of real-world CR program achievement of process and outcome QIs in Canada, using the Canadian Cardiac Rehab Registry (CCRR). The CR QIs were developed through the Canadian Cardiovascular Society's Best Practice Methodology. After reconciling the QI with CCRR definitions, it was identified that 14 (46.7%) of the 30 QIs could be assessed through the CCRR. There were 5447 patient records from 11 CR programs in the CCRR. Wait times exceeded the 30-day QI target, at a median of 84 days from referral to enrollment. Assessment of QIs of blood pressure (90%) and adiposity (85%) were high, however assessment of QIs for lipids (41%), blood glucose among patients with diabetes (23%), and depression overall (13%) were low. A majority of the participants (68%) achieved the half metabolic equivalent increase in the exercise capacity QI from CR program entry to exit. Of smokers, only 61% were offered smoking cessation therapy. Thirty percent of participants were offered stress management. The CR program completion QI was met in 90% of patients. Areas for care and quality improvement have been identified for the CR community in Canada. Efforts to engage more CR programs assess a greater number of QIs, and to feed back the findings to participating programs quarterly are currently under way.