Critical decision window for DMCs.

<p>Critical decision window for DMCs.</p

Interviewee pseudonyms and the capacity in which they served on a DMC.

<p>Interviewee pseudonyms and the capacity in which they served on a DMC.</p

"You have to keep your nerve on a DMC." Challenges for Data Monitoring Committees in neonatal intensive care trials: Qualitative accounts from the BRACELET Study

<div><p>Background</p><p>Data Monitoring Committees (DMCs) are essential to the good conduct of many trials. Typically they comprise a small expert group which monitors safety, efficacy, progress and early outcome data as trials recruit. DMCs can recommend protocol revisions and early stopping of a trial. As DMC meetings usually consider unblinded interim data confidentially, their deliberations are seldom exposed to research scrutiny. Although there have been some case studies from trials from mixed specialties which offer insights into some of the common issues faced by DMCs, we have, however, little empirical information about the challenges faced within specific clinical settings.</p><p>Methods</p><p>In-depth interviews with participants in the BRACELET Study on death and bereavement in neonatal intensive care trials produced qualitative accounts of experiences and views of a subgroup of 18 DMC members. These interviews explored views of DMC members in relation to the clinical context of neonatal intensive care and the conduct of neonatal intensive care trials.</p><p>Results</p><p>Interviewees felt that an understanding of both the neonatal intensive care setting and population was crucial in a DMC. They considered the neonatal intensive care research population especially vulnerable, and that outcomes that included both death and severe disability raised particular challenges rarely faced in other settings. In exploring these key outcomes they were mindful of the need to meet high scientific standards and the needs of babies in the trials and their families. DMC members discussed particular difficulties around the composite outcome of death and severe disability, especially when mortality data were available long before data on longer term disability. While statistical stopping guidance is helpful, DMC members described decisions about stopping, revising or continuing a trial being informed by a wider set of considerations and discussions than a pre-set p value. These included potentially competing needs of current trial participants and future patients, and reflections on the nature of benefit and harm. Given their cognisance of the potential impact and consequences of the decisions made by DMCs in this setting of life, death, and disability, interviewees commonly used the imagery of bravery, and described DMCs either holding or losing their nerve.</p><p>Conclusions</p><p>DMCs for trials in other fields may also face difficult ethical trade-offs in monitoring composite outcomes. The experience from this sample of DMC members suggest that for neonatal intensive care trials there are some very specific challenges seldom faced elsewhere. The vulnerability of the population, and the different timescales for essential data becoming available to inform decisions, presented particular challenges. We suggest that it is important to consider the challenges raised in other settings to better understand the complex work of these committees and to prepare future generations of DMC members.</p></div

Case reporting and completeness of data collection.

<p>Case reporting and completeness of data collection.</p

Risk factors for placenta accreta/increta/percreta.

*<p>Percentage of individuals with complete data.</p>¥<p>Includes myomectomy, dilation & curettage, surgical termination of pregnancy, evacuation of retained products of conception & manual removal of placenta.</p>‡<p>Adjusted for all factors in the table apart from socio-economic group, previous caesarean uterine incision type(s), previous uterine perforation and interval between last caesarean section and last menstrual period. When adjusting for age, BMI and parity, these variables have been treated as a continuous linear term in the analysis.</p

Risk factors for uterine rupture in women with prior delivery by caesarean section.

a<p>Percentage of individuals with complete data.</p>b<p>Adjusted for all factors in the table apart from socio-economic group, previous uterine incision type(s), previous caesarean uterine closure type(s), previous uterine perforation, and twin pregnancy. When adjusting for age, body mass index, parity, and number of previous caesarean deliveries, these variables have been treated as a continuous linear term in the analysis.</p

Risk factors for uterine rupture in women with prior delivery by caesarean section.

a<p>Percentage of individuals with complete data.</p>b<p>Adjusted for woman's age as a continuous linear term, ethnicity, body mass index as a continuous linear term, parity as a continuous linear term, number of previous caesarean deliveries as a continuous linear term, previous uterine surgery, interval between last caesarean section and last menstrual period as a categorical term, placenta praevia, and macrosomia.</p>c<p>Labour either not induced or induced without prostaglandin.</p

Symptoms and signs noted prior to diagnosis of uterine rupture.

a<p>Percentage of individuals with complete data.</p>b<p>Includes shoulder tip pain, scar tenderness, maternal tachycardia, and blood in abdomen.</p

Risk of uterine rupture according to the interval between the last caesarean section and start of current pregnancy.

<p>Adjusted for woman's age as a continuous linear term, ethnicity, body mass index as a continuous linear term, parity as a continuous linear term, number of previous caesarean deliveries as a continuous linear term, previous uterine surgery, placenta praevia, macrosomia, and planned mode of delivery.</p