Most of the parents surveyed (81%) believed their own child's participation in T1DCTs is important. Yet, less than 50% were significantly willing to enroll their children. Although parents described themselves as being more willing to enroll their children with diabetes, for the 18% who recalled being approached about enrollment, acceptance statistics were similar for both children with and without diabetes.
While most participating parents stated they received information about T1DCTs, the majority of parents did not recall being asked specifically to enroll a child in T1DCTs. It is possible that providers believed that they asked families, but that the phrasing was not understood as a specific offer to participate. These findings suggest that if we can reach the nearly 80% of parents who may not yet have been approached, patient enrollment in T1DCTs would increase.
A notable 36% of parents reported that the information they received about trials was not entirely straightforward, which had no correlation with parental education level. Perceived degree of ease required for understanding trial information correlated with WTEDC and WTEnDC, and it was a predictor for WTEnDC. Interestingly, a previous report of a screening study for T1D demonstrated that although a majority of mothers who enrolled their children were satisfied with the information they received about the study and regarded themselves as having understood the information, a significant proportion were either unsure or disagreed with several of the basic aims of the study 
. These findings highlights the importance of dedicating time to explain the process of trial participation, to answer questions, and to allay any misconcentions parents may have. It also suggests that development of specific adjunctive tools, such as scripts, may aid in communication and recruitment.
Although none of the sociodemographic data examined had a statistically significant correlation with willingness to enroll, financial concerns related to trial participation were of significance. A significant number of parents expressed worries of having to pay for research treatments and endorsed that lack or cost of transportation would influence enrollment decisions. Parents with lower income were more likely to endorse these concerns. These concerns may be particularly important in trials involving longer periods of time away from work and school such as trials with multi-day infusions. Therefore, when approaching parents about trial enrollment, it is worthwhile to discuss participation-related costs, perhaps even in situations where no direct costs are involved. Concerns about cost or lack of transportation also underscores the importance of coordinating research activity with regular doctor visits, and of offering any available assistance to minimize added financial and commitment burdens associated with trial participation.
Safety and comfort issues related to trial participation are of major concern for parents. Those who were more willing to enroll their children were less likely to be influenced by fear of side effects or to believe research may harm their children. Parents were less comfortable with trials involving more invasive, potentially painful protocols, or those that required tests and treatments that were not part of routine diabetes care. We found that a child's fear of receiving injections had an important influence over enrollment decisions for nearly 20% of parents. Injection fear in a child made parents significantly less comfortable with protocols that may be common aspects of T1DCTs such as blood draws, intravenous injections, vaccines, and blood transfusions. Nevertheless, intervention-specific fears may also contribute to discomfort with these protocols. Vaccines, for example, have generated considerable opposition among the public for complex reasons since their initial introduction 
Several studies have shown that parents generally have a poor awareness and understanding of pediatric randomized clinical trials 
. Importantly, the rationale for the random allocation of treatment and the use of placebo is generally poorly understood not only by parents, but also by adult patients, adult physicians, and pediatricians 
. The implication is that the presence of randomization and a placebo group, integral aspects of high quality research, are often barriers to participation 
. Results from our study agree with these reports. Only a minority of parents were comfortable with the possibility of their child being randomised to a placebo arm. Comfort with placebos had a strong positive correlation with and was predictive of willingness to enroll both a child with diabetes and an unaffected child in T1DCTs. Therefore, we need to address any existing misconceptions about placebo allocation when discussing trials with parents.
A previous study revealed that despite overall support for pediatric research, many parents are reluctant to involve their own children 
. Although risk-benefit considerations were an important aspect of decision-making regarding trial participation 
, Caldwell and workers found that many parents struggled with the responsibility of consent by proxy because of concerns about the unknown or unexpected future side effects 
. Likewise, we observed a disconnect between parents' overall belief in the importance of trial participation and actual willingness to enroll children in studies. In our study, we find that parents' decisions regarding trial enrollment are fundamentally driven by a desire to balance potential benefits for their children with risks of side effects or potential harm from trial participation. Nevertheless, some parents were uncomfortable with the responsibility surrounding consent by proxy, which negatively impacted willingness to enroll their children. Furthermore, our results showed that discomfort with consent by proxy was a strong predictor for willingness to enroll. With regard to parents' assessment of risk-benefit, one may also hypothesize that this evaluation may be skewed immediately after diagnosis. We did not administer the survey to parents at the time of diagnosis, but many respondent families were within the first year of diagnosis. We found no correlation between willingness to enroll and the time since diagnosis. Thus, if attitudes and trial acceptance are altered immediately post-diagnosis, this effect wanes rapidly. This possible renormalization of attitudes could relate to the extensive social network of established T1D families that supports newly diagnosed families.
Our results emphasize the importance of a healthcare provider's role in the recruitment process for T1DCTs. In previous studies, parents acknowledged seeking their pediatrician's advice regarding trial participation because they trust their opinion and medical knowledge 
. Tercyak and coworkers also found that provider behavior influences adolescent acceptance of randomized clinical trials for T1D 
. In our study, parents reported the majority of information they received about T1DCTs came from their pediatric diabetes physician. Similar to previous reports, we saw that most parents believe that doctors have the best interest of patients in mind when approaching them about trial enrollment. This belief was an important predictor of both WTEDC and WTEnDC, further highlighting the importance of the relationship between pediatricians and their patients' families in T1DCT enrollment.
Several limitations of the present study must be acknowledged. Our study population was relatively homogenous. Similar to the study reported by Caldwell et al. 
, respondents were largely white females. Likewise, we also determined that most pediatric TrialNet enrollees at our institution are White, and their consenting parents were most often mothers. Therefore, we seem to have captured the attitudes of parents with similar demographic characteristics as those who enroll their children in observational studies, but are reluctant to enter interventional trials. It is possible that mothers are the parents who most frequently bring their child to our diabetes clinic, and are thus more likely to be the ones available to fill out surveys and sign consent forms for trial enrollement. Nevertheless, fathers may influence decisions regarding a child's trial enrollment in ways that differ from that of mothers, making it important to ascertain their attitudes and to involve them in the educational and consent processes. It may also be the case that fathers and ethnic minorities are in fact just as likely to accompany their children to clinic, but are not asked as often to participate in studies. This is less likely given that the survey was made available to all parents and guardians who brought their children to our clinic. Another possibility is that fathers and ethnic minorities are less likely to be willing to participate. If fathers, minorities, or other non-responders differ in their attitudes towards T1DCTs compared to those who responded, there may be non-response bias effects. Our study was not powered to detect these differences. Although we have limited representation of responses from racial and ethnic minorities, we find it reassuring that recruitment rates for African Americans in our study (7%) are very similar to the prevalence of African American children with type 1 diabetes in the United States, according to the SEARCH for Diabetes in Youth Study (9.2%) 
. It should also be noted that our study population is reflective of the patient population served by our institution, which may not be universally applicable.
By undertanding parents' attitudes, we can improve T1DCT recruitment, both in the sense of attaining higher enrollment rates and of making trial participation a positive experience, thereby encouraging adherence to trial protocol and participation in future studies. Although baseline willingness to enroll is not high, opinion about T1DCTs may be improved by increasing education efforts. We have identified several key modifiable parental factors concerning T1DCTs: difficulty understanding information about T1DCTs, parental concerns regarding potential costs associated with participation, discomfort with placebo treatment, and fears of their child serving as “guinea pigs” for research. Additionally, communicating more clearly and openly with parents may help address any potential conflict with consent by proxy or emotional responses to their child's illness, which has the potential to positively impact T1DCT participation.