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Psychological Screening of Children for Participation in Nontherapeutic Invasive Research
Ann Marie McCarthy, PhD, RN, PNP;
Lynn C. Richman, PhD;
Robert P. Hoffman, MD;
Linda Rubenstein, PhD
Arch Pediatr Adolesc Med. 2001;155:1197-1203.
ABSTRACT
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Background The need for children to participate in research has raised concerns
about ethical issues surrounding their participation.
Objectives To describe a protocol of preresearch psychological screening and postresearch
outcomes and to present the results of the screening process for a nontherapeutic,
invasive research study.
Design and Setting Descriptive study carried out at The University of Iowa Hospitals and
Clinics, Iowa City.
Participants Twenty-eight children (mean age, 10.6 years) were screened, with 4 not
completing the research study and another 4 unavailable for psychological
follow-up.
Main Outcome Measures Prescreening interviews with parent and child and screening measures
of appropriate child cognitive abilities and behavior; postscreening parent
and child questionnaires.
Results Of the 4 children who did not complete the research study, 3 were identified
with increased anxiety during the screening and were advised to not participate
in the study. The primary motivator for participation was monetary reimbursement
(14 parents [82%]; 15 children [75%]), followed by altruistic reasons (10
parents [59%]; 4 children [20%]). Before participating, none of the children
reported concerns related to participating in the study. However, on follow-up,
9 (45%) of the children reported that they had had concerns before participating.
Follow-up assessment showed that parents underestimated their children's concerns
related to sexual development assessment and intravenous insertion.
Conclusions Children with increased anxiety may not be appropriate participants
in potentially anxiety-provoking research. Children's reports of concerns
may change from preparticipation to postparticipation, and discrepancies may
exist between parent and child reports of concerns with research participation.
Further research is needed to ensure children's safe participation in research.
INTRODUCTION
THERE IS A NEED for children to participate in research, as recognized
by the recent National Institutes of Health research guidelines that require
inclusion of children in studies, unless there are overriding reasons to exclude
them.1 It has also been established by the
US Department of Health and Human Services2
that children require additional protection, beyond adult guidelines, when
involved as subjects in research. According to federal guidelines,2 a child may participate in research if informed consent
(permission to participate) is obtained from the parent or legal guardian,
the child assents (agrees), and the research falls into one of the risk categories
established for research with children.1 Each
institutional review board (IRB) sets the age at which a child should provide
assent to participate; usually this is 7 years or older.3
A number of issues need to be clarified in following these government
mandates and additional protections for children. One issue is that of a child's
decision-making ability related to assent.4
For adults, elements of informed consent include the ability to understand,
show evidence of reasonable choice, and hypothesize possible reasons for withdrawal.5, 6 Chronological age does not necessarily
guarantee a related degree of cognitive ability or decision-making skills.
When child assent is considered,7, 8, 9, 10
developmental status, not just age, must be assessed. This is not, however,
just a matter of measuring a child's cognitive ability.4
There is also concern regarding the child's emotional state and the influence
of social desirability to participate.8 For
example, there is the dilemma of parents who volunteer and encourage their
children to participate in research, raising concerns of whether the the child
is giving informed assent or conforming to parental expectation.7, 9
While there has been controversy over child participation in research,6, 11, 12 there is developing
agreement by many researchers, ethicists, and IRBs that children should be
allowed to participate in research, including nontherapeutic research, where
there is no direct benefit to the child, if there is minimal risk or only
minor increase in minimal risk to the child. However, there are ethical concerns
related to the need to protect children participating in such research. As
more children are involved in research studies, recognized procedures for
identifying children who are appropriate for such research need to be developed.
The purpose of this article is to describe a psychological screening protocol,
developed at the request of a human subjects IRB, for prestudy screening of
children involved in a nontherapeutic, invasive research study and to present
results of the prestudy screening and follow-up data obtained on the children
and parents who participated.
SUBJECTS AND METHODS
This study was developed in response to a request by an IRB related
to a nontherapeutic, invasive research study involving children. The section
that follows presents a description of the proposed nontherapeutic research
study, the IRB's response, and the involvement of psychologists to assist
with enrollment and follow-up monitoring of subjects.
NONTHERAPEUTIC INVASIVE RESEARCH STUDY
The purpose of the research being reviewed by the IRB was to explore
longitudinal changes in peripheral and hepatic insulin sensitivity in prepubertal
and early pubertal children and to determine predictors for changes in insulin
resistance and growth velocity. This study will be referred to as the Insulin
Sensitivity Study.13 The subjects of the Insulin
Sensitivity Study, carried out by one of us (R.P.H.), were to be 2 groups
of healthy children, aged 8 to 13 years, one group classified as Tanner stage
1 for breast or genital development and the second group classified as Tanner
stage 2. Each child would be admitted overnight 4 times, during 18 months,
to the Clinical Research Center at the hospital. During each hospitalization,
the child would be examined to identify Tanner stage of pubertal development,
height, weight, and body fat. An intravenous line (IV) would be placed in
each arm to have blood drawn for measurement of growth hormone, glucose, and
other relevant variables, and for dextrose bolus. Subjects would receive $50
per hospital admission.
The IRB members questioned the impact on the children of overnight admissions
to the Clinical Research Center and the accompanying tests. However, they
believed it ikely that the study would yield important generalizable knowledge.
Therefore, in an effort to minimize this potential minimal risk to the children
in the proposed study, the IRB requested that pediatric psychologists (A.M.M.
and L.C.R.) advise the investigator about procedures for identifying subjects
appropriate for inclusion in the study and ensure that participants were followed
up to determine any possible after-study effects.
PSYCHOLOGICAL SCREENING PROTOCOL
We developed a brief psychological screening protocol, outlined in Table 1, to identify children who might
be at risk for psychological distress by being in the study. Little information
was available in the literature on screening children for involvement in nontherapeutic,
invasive research. Therefore, on the basis of our experience, we designed
a protocol that included interviewing the child and parent separately and
screening the child for age-appropriate cognitive abilities and behavioral
concerns. Instruments were included that are commonly used clinically and
in research. The protocol took approximately 45 minutes to complete. Separate
compensation for participation in the psychological screening sessions was
not provided.
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Table 1. Psychological Screening Protocol*
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The purpose of the interviews was to clarify both the child's and the
parents' understanding of what was involved in participating in the study.
The interviews were carried out on the day the families came to the medical
center to discuss involvement in the study. The medical researcher met with
the family; reviewed the study, including the psychological screening component;and
obtained parental consent and child assent. Then the psychologist interviewed
the parent and child separately. Each was asked to describe how he or she
learned about the study, the motivation for participating, the parent's plans
to spend the night during the child's hospitalizations, the child's experiences
with hospitalization and separation from family, child developmental or academic
concerns, and concerns the child or parent might have related to the study.
The protocol for the study was reviewed to clarify that the participants knew
what procedures would be carried out, that participation was voluntary, and
that they might drop out of the study at any time.
Cognitive ability and behavioral concerns were screened after the interviews.
To verify that the children had age-appropriate verbal intellectual ability
to understand the basic aspects of the research project, cognitive skills
were screened with the Wechsler Intelligence Scale for Children–III
subtests, similarities and information.14 Ability
to read the assent forms was confirmed by screening the children's reading
ability with the Wide Range Achievement Test–3 to ensure that each child
had reading skills at the third grade level or above.15
Once it was ascertained that the child showed adequate understanding, the
child was screened for possible internalizing behavior problems, specifically
increased anxiety and depression. The procedures required for the proposed
study were thought to be potentially stressful for highly anxious children.
The younger children (8-11 years) completed the State-Trait Anxiety Inventory
for Children (STAIC)16 and the Children's Depression
Inventory,17 and the older children (12-13
years) completed the Symptom Checklist-90-R.18
This information was supplemented by having parents complete the Pediatric
Behavior Scale19 to identify both internalizing
and externalizing problems. Before screening, we decided that if a child demonstrated
problems in understanding the study protocol, showed diminished cognitive
abilities, or scored greater than the 90th percentile on measures of anxiety,
depression, or parent-reported behavioral concerns, then the child would not
be considered an appropriate candidate to participate in the study. Two pediatric
psychologists (A.M.M. and L.C.R.) individually reviewed data on each child,
with the above criteria considered, and made recommendations to the family
and the principal investigator of the research study (R.P.H.).
After completion of the Insulin Sensitivity Study, each child and a
parent were contacted to complete a questionnaire describing their experiences.
Families were mailed 2 follow-up questionnaires, one to be completed by the
child who had been in the study and the other to be completed by a parent.
A follow-up reminder was mailed to families who had not returned the questionnaires
3 weeks after the first mailing. The follow-up questionnaires included questions
listed in Table 1. Likert questions
on a scale of 1 to 5 were included to measure comfort with assessment of sexual
development, IV insertions, blood draws, and staying overnight for each of
the 4 hospital stays.
STATISTICAL METHODS
All descriptive statistics were generated by means of SAS statistical
software.20 Because of the small sample size
in our data set and the descriptive nature of our report, most statistical
tests and measures of agreement were generated with StatXact4,21
a software package for analysis of small data sets. Cochran-Mantel-Haenszel
methods were used to assess stratified data with nominal and ordinal categories.20 Exact nonparametric methods included Wilcoxon rank
sum test for 2 independent samples, Fisher exact test for 2 independent samples,
Page test for related samples and ordered categorical data, and Kruskal-Wallis
methods for multiple independent samples and ordered categories.21
Magnitude of agreement was measured with Cohen  for data with nominal
categories and a weighted for data with ordered categories.22, 23
RESULTS
PARTICIPANTS
Twenty-eight children, from 24 families, were screened for participation
in the Insulin Sensitivity Study. There were 15 boys (54%) and 13 girls (46%),
with a mean age of 10.6 years (SD, 1.8 years; range, 8-14 years) and a mean
grade level of 5.2 (SD, 1.7; range, second to eighth). None of the children
had repeated a grade, although 2 were receiving resource room assistance in
school. All of the parents had at least a high school education, with 33%
of the fathers and 38% of the mothers having a college degree or higher. Only
2 fathers participated.
Of the 28 children screened, 24 participated in the Insulin Sensitivity
Study. Four children who were screened did not participate in the study, and
4 children who did participate were unavailable for follow-up of the psychological
screening. This left 20 children and their parents from 17 families who completed
the follow-up questionnaires.
PRESCREENING
Parent Interviews
The parents reported that they learned about the study primarily from
newspapers (14 parents [58%]) and a friend or family member (11 [46%]). The
2 reasons most frequently given for parents wanting their child to participate
in the research study were for the financial reward (13 parents [54%]) and
altruistic reasons (10 [42%]). Most parents (17 [71%]; missing data in 7 [29%])
believed that they and their children were prepared to participate in the
research and recognized the voluntary status of this research (23 parents
[96%]). Generally, parents planned to stay with their children during the
hospitalizations (17 [71%]).
Child Interviews
In separate interviews with the children, the children reported learning
about the study from their parents. All of the children stated that they understood
that participation in the study was voluntary, and none of the children reported
concerns about being in the study.
Cognitive Screening
All of the children were within normal ranges on cognitive and reading
testing. The mean standard score on the Wechsler Intelligence Scale for Children–III
information subtest was 11.5 (SD, 1.4), and on the similarities subtest, 11.6
(SD, 2.0) (average subtest scores are 10). The mean standard score on the
Wide Range Achievement Test–3 reading test was 99.9 (SD, 10.9) (average
score is 100).
Anxiety and Depression Screening
Of the 28 children, 20 were in the age range to complete the STAIC and
the Children's Depression Inventory. On the STAIC, the mean state score (current
level of anxiety) was 26.8 (SD, 4.5), with 18 children scoring below the mean
(less anxiety) and 2 children scoring more than 1 SD above the mean (more
anxiety). The 2 children who were more than 1 SD above the mean were among
the 4 children who did not complete the research study. The mean trait score
(general level of anxiety) was 30.8 (SD, 6.8), with 15 children scoring below
the mean, 1 scoring slightly above the mean, and 3 scoring more than 1 SD
above the mean (trait data missing on 1 child). The 3 children who were more
than 1 SD above the mean were children who did not complete the research study.
On the Children's Depression Inventory, the mean percentile score was
24.8 (SD, 26.3; range, 2-87). Of the 20 children, 18 were in the normal range
and 2 were borderline to above (more depression) the normal range (more than
+1 SD). The child with a borderline score was within the normal range on all
other measures, related some of her concerns on this measure to her dislike
of school, had a sibling participating in the study, and had successfully
participated in a similar research study. She successfully completed participation
in this study. The child with an elevated score also had elevated scores (+1
SD) on the STAIC and was among those who did not complete the study. Only
8 of the children were in the age range for the Symptom Checklist-90-R. All
8 children scored in the normal range.
Behavior
Parents completed a Pediatric Behavior Scale for each child. On this
instrument with 24 subscales, 13 of the 28 children were reported by their
parents to be at or above the 90th percentile on at least 1 subscale. However,
11 of these children had elevated scores on only 1 or 2 scales, and typically
these elevations were related to concerns with eating, clumsiness, arousal,
or school issues. All 11 children were in the normal range on the self-report
measures of anxiety and depression. Of the 2 remaining children, 1 child had
a diagnosis of attention-deficit/hyperactivity disorder, was treated with
methylphenidate hydrochloride, and had elevated scores on subscales related
to attention-deficit/hyperactivity disorder and school. He was in the normal
range on the self-report measure of anxiety and depression and successfully
participated in the research study. The final child had elevated scores on
scales related to anxiety, self-esteem, attention, and school; displayed increased
anxiety on self-report; voiced concerns about needles; and was one of the
children who did not complete the study. Interestingly, only 1 parent reported
increased child anxiety.
PRESCREENING: CHILDREN WHO PARTICIPATED VS THOSE WHO DID NOT
As stated earlier, of the 28 children screened for participation in
the Insulin Sensitivity Study, 24 actually participated and 4 did not. The
4 children who did not participate included 2 boys and 2 girls, aged 8 to
13 years with a mean age of 10.9 years (SD, 2.2 years) in grades 3, 4, 6,
and 8. These 4 children did not differ on cognitive measures from the 24 children
who did participate, but 3 of the 4 children had elevations on measures of
anxiety. Means, SDs, medians, and ranges for anxiety scores and statistically
significant differences are presented in Table 2.
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Table 2. Descriptive Statistics of State-Trait Anxiety Scores by Subgroups
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The researcher and parents of the children with elevated anxiety scores
were informed of the findings and cautioned regarding the child's participation
in the study. The parents of the first child with increased anxiety initially
decided to continue the child's participation in the Insulin Sensitivity Study.
However, during the first hospitalization, the child became ill when the IV
insertion was attempted and subsequently dropped from the study. When 2 other
children were noted to have elevations on anxiety, depression, and/or a fear
of needles the families were advised, with the support of the researcher,
to not participate in the study and did not. The fourth child, who was in
the normal range on all screening measures, dropped from the study because
of difficulty starting the IV during the first hospitalization.
FOLLOW-UP QUESTIONNAIRES
Twenty children (mean age, 10.8 years; SD, 1.6 years) and parents from
17 families completed the follow-up questionnaires. Three children who participated
in the research but who were unavailable for follow-up scored significantly
lower (less anxious) on the STAIC measure of anxiety than did those who completed
the study and 3 of the 4 who dropped out. Descriptive statistics for the anxiety
scores are presented in Table 2.
Where possible, follow-up data obtained on the 20 children and their
17 parents were compared (Table 3).
The primary motivation for participation in the study was financial reimbursement,
with 14 (82%) of the parents and 15 (75%) of the children reporting this as
a reason for participating. The second reason given was an interest in contributing
to medical knowledge; however, this was more of a factor for the parents (10
parents [59%]) than for the children (4 children [20%]). Another area of interest
was the concerns children reported related to participating in the study.
During the prestudy interview, none of the children reported concerns; however,
after participation in the study, 9 (45%) of the children reported concerns,
including worries about staying overnight, needles, physical assessment, side
effects, and overall safety.
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Table 3. Parent and Child Follow-up Responses
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Likert questions were included that asked the child and the parent to
rate their level of comfort, on a scale of 1(very comfortable) to 5 (not at
all comfortable) on 4 aspects of participation in the study for each of the
4 hospitalizations. Children rated their own comfort levels, while parents
rated their perceptions of their children's comfort levels. The 4 aspects
rated were Tanner stage assessment (assessment of sexual development carried
out by a physician of the subject's sex), IV insertion, blood draws, and staying
overnight. The median scores for the 4 aspects across the 4 hospitalizations
ranged from 1.0 to 3.0 for the children and from 1.0 to 2.0 for the parents,
indicating overall low levels of concern by both groups. Over time, levels
of comfort improved in all areas as reported by both parents and children.
The highest levels of concern for both groups were noted for Tanner staging
and IV insertion. The parents' perceptions were that the IV insertion was
the most difficult for their children. Although the children reported IV insertion
as a concern, they reported that assessment of sexual development was the
most concerning aspect of the study across all 4 hospitalizations. No differences
were noted in levels of concern between children who had a parent stay with
them during a hospitalization and children who did not.
Agreement between parents' and children's perceptions of comfort were
assessed via and weighted coefficients for magnitude of agreement
between parent and child pairs.22 Table 4 shows the proportions of parents
underestimating their child's discomfort for the 4 aspects of study participation
across the 4 hospitalizations. For example, parents tended to rate children
as being at 1 or 2 on the comfort scale, while the children's self ratings
were higher, 2 or 3, indicating more discomfort. For assessment of sexual
development, parents underestimated their child's concern for all 4 visits,
from 50% of the time at the first visit to 29% of the time at the last visit.
For assessment of IV insertion, parents tended to underestimate their child's
concerns for the first few visits, but for the last visit, 5 of 15 parents
overestimated their child's concern, 2 underestimated, and 8 agreed with their
child's assessment of their level of concern. Parents were less likely to
underestimate their child's concerns about blood draws and staying overnight,
with proportions of underestimation ranging from 6% to 25% across the 4 hospitalizations
for these 2 experiences. Except for 4 coeffecients that reflected
the documented paradox of high , low agreement, or low , high
agreement,24 coefficients for assessment
of sexual development and IV insertions were less than 0.60, indicating fair
to moderate agreement, while for blood draws and staying overnight they ranged
from 0.64 to 0.85, indicating more substantial agreement in these areas.23
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Table 4. Proportion of Parents Underestimating Child's Discomfort*
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Differences in children's perceptions of comfort based on their sex
were also assessed. There were no significant sex differences in children's
level of comfort responses across the 4 hospitalizations for overnight stays,
blood draws, and IV insertion (Page test, Kruskal-Wallis test, and Cochran-Mantel-Haenszel
methods). Although discomfort levels decreased for both sexes across all hospitalizations,
girls and boys rated their comfort levels differently for the Tanner assessment.
At visit 1, 5 boys and 1 girl reported discomfort levels of 4 or greater.
For the second and third hospitalizations, 6 boys indicated ratings of 3 or
greater but only 3 girls reported similar reactions. At the last visit, all
of the girls reported comfort levels of 1 or 2, but 6 of 11 boys reported
comfort levels of 3 or 4. At each visit, except the first, the distribution
of comfort responses was significantly different between boys and girls (Fisher
exact 2-tailed test, P<.05), with boys having
greater discomfort.
Before starting the Insulin Sensitivity Study, 17 (71%) of the parents
reported they planned to stay with their children during the hospitalizations
required for the study. On follow-up, parents were asked whether they stayed
during each of the hospitalizations. Of the 17 parents who responded to the
follow-up questionnaire, 14 had planned on staying with their child overnight,
but only 10 did stay during the first hospitalization. This number dropped
during subsequent hospitalizations, with only 4 parents in this group staying
overnight during the fourth hospitalization. Overall, across the 4 hospitalizations
for 20 children, a parent stayed with their child 57% of the time. This ranged
from a parent staying during 77% of the first hospitalizations to 42% by the
fourth hospitalizations.
None of the children or parents reported emotional or behavioral sequelae
after participation in the study that they attributed to being in the study.
All of the parents stated that they would allow their children to participate
in future research, and only 1 child reported not wanting to be in research
in the future "if there are IVs."
COMMENT
This study within a study was undertaken at the request of the IRB to
try to identify children potentially at risk from participating in nontherapeutic,
invasive research. The psychological screening process piloted indicated that
parents and children understood the voluntary nature of the study and the
procedures involved in participating. Children demonstrated normal aptitude
and achievement, supporting developmentally appropriate understanding of the
processes involved. However, behavioral screening suggests that children with
increased anxiety may be at risk in participating in this type of study. If
trait anxiety is already high, potentially anxiety-provoking experiences such
as hospitalization and invasive procedures may elevate state anxiety to a
detrimental level. Therefore, monitoring anxiety ensures not placing a child
who is already anxious in an anxiety-provoking situation needlessly. Although
only 1 child who showed an increase in anxiety began to participate in the
study and then dropped out, it is unknown what the fate of the other 2 children
with increased anxiety, who were advised not to participate in the study and
did not, might have been.
Financial reimbursement was the primary motivation for participation
in this study. Interestingly, parental report that financial reimbursement
was a reason for participation increased from 54% to 82% on follow-up questioning.
Contributing to medical knowledge was a low motivator for the children, but
a stronger motivator for the parents. Although money is typically used in
our society to pay for services, these results raise 2 questions. First, is
money too powerful a motivator? It is possible that children may be coerced
to be in a study by parents to obtain the financial reimbursement. Children
in lower socioeconomic groups may be particularly at risk for this form of
coercion. Practices of monetary reimbursement for children may need to be
reassessed. It may be that providing less money, providing the money before
participation, or providing nonmonetary rewards may be less coercive to families.
Second, are parents indirectly persuading their children to participate in
research because of the parent's interest in doing something for the greater
good (altruism by proxy)? While this may appear to be positive, it may not
be in the child's self-interest.
Two assumptions often made in pediatric health care are that children
are truthful when they provide information and that parents know their children
and, therefore, are able to accurately represent them. In this study, none
of the children reported concerns with being in the study before participation,
but after completion of the study, 45% reported that they had concerns before
participation. The children may not have felt comfortable with the investigators,
or, on the basis of their prior experience, may not have understood the extent
of participation. The discrepancies between parent and child report of concerns
with various aspects of the study suggest that parents may not be able to
accurately represent their child's feelings. Interestingly, the children,
particularly the boys, were more distressed by assessment of sexual development
than perceived by their parents. While parental right to provide consent for
their child is not questioned, the extent to which parents are able to accurately
recognize their child's concerns is questioned.
As noted earlier, it is generally accepted that children should be allowed
to participate in nontherapeutic research. The majority of the children in
this study appeared to successfully participate and voiced interest in participating
in similar research in the future. However, concerns regarding the process
of this involvement exist. This pilot study provides beginning information
on this participation. While children appear to understand the research process,
they may not be totally forthcoming in their concerns about participating.
However, the unspoken concerns of children do not necessarily interfere with
their positive participation in research. Researchers cannot assume that parents
will be accurate in their assessment of their children's concerns. While children
with increased anxiety may not be appropriate participants in potentially
anxiety-provoking research, exclusion of these children may result in a sample
selection bias that may be detrimental to some research projects. Clearly,
there needs to be further research on child participation in research.
AUTHOR INFORMATION
Accepted for publication August 2, 2001.
This study was supported by Genentech Foundation for Growth and Development,
Charlottesville, Va, and grant NIH RR000059 from the Clinical Research Center,
The University of Iowa, Iowa City.
From the College of Nursing (Drs McCarthy and Rubenstein) and Divisions
of Pediatric Psychology (Dr Richman) and Pediatric Endocrinology (Dr Hoffman),
Department of Pediatrics, College of Medicine, The University of Iowa, Iowa
City. Dr Hoffman is now with the Department of Pediatrics, Columbus Children's
Hospital, Columbus, Ohio.
Corresponding author and reprints: Ann Marie McCarthy, PhD, RN, PNP,
College of Nursing, Nursing Bldg, Room 430, 50 Newton Rd, The University of
Iowa, Iowa City, IA 52242 (e-mail: ann-mccarthy{at}uiowa.edu).
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