Dear Editor

The study by Stenson et al. serves an important purpose in quantifying the reactions and recall of parents regarding the informed consent for enrolling their newborn infants in randomized controlled trials soon after birth(1).

These results are not unexpected, given similar findings from previous research in this area(2, 3), but may have limited usefulness in understanding the reasons for the lack of parental recall, and for developing interventions to improve the memory of discussions regarding research consent.

For the most part, these studies have focused on the affective reactions (anxiety, satisfaction) of the parents approached for consent, rather than elements of the study design contained in the consent form. Also, some methodological weaknesses could be addressed by additional attempts to contact the non-responders, by conducting telephone interviews to obtain greater insight into the reasons for the parental opinions expressed, by detailed description of the process for obtaining consent, and perhaps by studying groups that were randomized to different therapeutic interventions in a blinded manner.

Complementary findings were noted in a similar study conducted at one site participating in the NEOPAIN Trial. Ballard and colleagues at University of Kentucky contacted the parents of ventilated preterm neonates (23-32 weeks gestation at birth) who had been randomized to masked study drug infusions containing either morphine or placebo solutions(4).

The process of obtaining consent was standardized, with attempts to obtain prenatal consent, at which time the consent form and a brief summary of the study protocol were given to the parents. Their willingness to participate was confirmed postnatally before enrollment of their infant.

If the mother delivered soon after admission, the consent process occurred postnatally, but usually involved more than a single contact with the parents. We firmly believe that informed consent “process” represents an ongoing dialogue between parents and the clinical staff rather than a single interview.

Ballard and colleagues developed a novel questionnaire designed to evaluate several different elements of the consent form. They tested the reliability of this questionnaire, made up to five attempts to contact parents, and interviewed them in person or on the phone. Open-ended questions were framed to examine parental understanding of the purpose of the study; its benefits and potential risks. Parents were asked to describe what the investigators wanted to do to their baby and whether they could withdraw their infant from the study at any time.

The response rate was similar (70%) to previous studies. 5 of 64 (7.8%) parents had no recall of the NEOPAIN study or of signing consent; those who remembered signing consent could accurately remember whether they signed consent before or after delivery (90%); 68% of these knew the purpose of the study; 95% of these could verbalize potential benefits but only 5% could recall the potential risks of the study.

A large number of parents (37.5%) did not recall their right to withdraw their infant from the study, and the time intervals from signing the consent form to completion of this questionnaire had no effect on their understanding of the study purpose (p=0.26), knowledge of its benefits (p=0.41) or risks (p=0.27), or the voluntary nature of the study (p=0.95).

Mothers were more likely than fathers to understand the purpose of the study (p=0.02) and seemed to know more about its potential benefits (p=0.07). The administration of magnesium sulfate appeared to have minimal effect on the mother’s recall of the study, despite its well-known effects on attention and memory(5). Most parents enrolled their infants in hopes of helping their baby and less than half of the parents expressed any specific fears about the study. All parents were willing to enroll their child again if given the opportunity, although only 2 of 64 (3%) parents met all the criteria used for defining the validity of informed consent.

Based on these results we propose that the informed consent process needs to: [a] include the mothers as much as possible, [b] form the basis of ongoing dialogue, [c] talk more about the potential risks of any new therapeutic intervention, [d] be less burdened by the complexity and excessive length of legalistic language in the consent form, [e] be complemented by a brief summary of the study protocol (preview or post hoc), and [f] be conducted in the presence of a witness, preferably some one trusted by the patient’s family (relative, pastor, neighbour, etc.).

How these recommendations are incorporated into routine research practices will be difficult and controversial. According to Benjamin Franklin, however, “the ills of controversy are temporary, but the benefits are permanent.”

References

(1). Stenson BJ, Becher JC, McIntosh N. Neonatal research: the parental perspective. Archives of Disease in Childhood: Fetal & Neonatal Edition 2004;89(4):F321-F324.

(2). Mason SA, Allmark PJ. Obtaining informed consent to neonatal randomised controlled trials: interviews with parents and clinicians in the Euricon study. The Lancet 2000;356(9247):2045-2051.

(3). Ellington M, Jr., O'Reilly D, Allred EN, McCormick MC, Wessel DL, Kourembanas S. Child health status, neurodevelopmental outcome, and parental satisfaction in a randomized, controlled trial of nitric oxide for persistent pulmonary hypertension of the newborn. Pediatrics 2001;107(6):1351-6.

(4). Ballard HO, Shook LA, Desai NS, Anand KJS. Neonatal research and the validity of informed consent obtained in the perinatal period. Journal of Perinatology. 2004;(In press).

(5). Ghia N, Spong CY, Starbuck VN, Scialli AR, Ghidini A. Magnesium sulfate therapy affects attention and working memory in patients undergoing preterm labor. American Journal of Obstetrics & Gynecology 2000;183(4):940-4.