PEDIATRICS Vol. 118 No. 4 October 2006, pp. 1616-1622 (doi:10.1542/10.1542/peds.2006-0585)
ARTICLE |
Recruitment Bias in a Population-Based Study of Children With Cerebral Palsy
a School of Nursing and Midwifery, Queen's University Belfast, Belfast, Ireland
b Greenpark Healthcare Trust, Musgrave Park Hospital, Stockman's Lane, Belfast, Ireland
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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OBJECTIVE. The purpose of this analysis was to assess recruitment bias in a population-based study of locomotor ability in children with cerebral palsy.
METHOD. A population-based case register was used as a sampling frame and was considered a highly ascertained record of children with the condition. A twin track approach to recruitment for the Locomotor Study was adopted through: (1) a specialist orthopedic service and (2) a community pediatric network on behalf of the case register. The subjects included children with cerebral palsy aged 4 to 16 years in 2003, able to walk 
10 m, and a resident in Northern Ireland, as well as their parents.
RESULTS. The Orthopaedic Service identified clinically distinct children with cerebral palsy in terms of type, severity, age, and geographic residence. More families responded to an invitation, and more were ultimately recruited into the study via the Orthopaedic Service compared with a case register using community pediatric contacts. Overall, 37.8% of the eligible cerebral palsy population participated in the Locomotor Study, but there was no evidence of any systematic biases in demographic or key clinical characteristics when compared with nonparticipants. One follow-up reminder led to an increase in recruitment of 10%.
CONCLUSIONS. Care must be taken in the recruitment of children with cerebral palsy through clinic-based populations, although these routes may prove more successful in follow-up. Provided they are comprehensive, case registers have a valuable contribution to make to clinical research by providing a sampling frame including information on baseline characteristics of an affected population.
Key Words: recruitment • cerebral palsy • case register • bias
Abbreviations: NICPR—Northern Ireland Cerebral Palsy Register • GMFCS—Gross Motor Function Classification System • IQ—intelligence quotient • POS—Pediatric orthopedic service • CI—confidence interval
Cerebral palsy is a leading cause of significant physical disability in childhood1 and refers to a collection of conditions primarily affecting motor function and posture caused by damage to the developing brain.2 The clinical presentation of the cerebral palsies can change over time, although few studies have investigated the "natural" history of the condition and the progression of function abilities. One of the main challenges to undertaking this type of research is obtaining sufficiently large and representative samples of children to ensure the external validity of the findings. Here we report on the recruitment of children with cerebral palsy into a population-based study of locomotor ability (the Locomotor Study) and evaluate the extent to which those participating in the study were representative of those eligible to take part.
The way in which subjects are identified, approached, and respond to invitations to participate in research can be a major source of bias in epidemiologic and clinical studies3,4 and, therefore, important for researchers to evaluate. Systematic differences in the characteristics of those participating in research compared with those who do not have been reported and include clinical, social, and ethnic biases.3,5–8 Different factors may be responsible for potential subjects being "lost" to research, and strict ethical guidelines often prevent researchers from asking subjects directly about why they do not respond, refuse, or opt out of research. Despite these difficulties, the details of recruitment of clinical populations are either seldom or inadequately reported in the literature.9,10 This is a lost opportunity in terms of affording prospective researchers the benefits of experience in recruiting a particular population using specific recruitment strategies.
Researchers assessing potential bias in study samples usually assess participants' baseline characteristics against some other "benchmark," like the characteristics of others attending the clinic8 or data published in the literature.11 The conclusions drawn, however, are dependent on the completeness and integrity of the benchmark used. At the time of recruiting for the Locomotor Study, we had access to a geographically defined case register of children with cerebral palsy (the Northern Ireland Cerebral Palsy Register [NICPR]).
The NICPR is a confidential record of every child with cerebral palsy born in Northern Ireland since 1977 or resident in the area since 1992 (managed by J.P.). Completeness of the NICPR was judged partly by the high rate of multiple notification (>70% of cases) and by the absence of systematic biases by demographic variables and prevalence rates comparable to other reports from around the world.1,12,13 Furthermore, the majority of data collection was undertaken without a requirement for parental consent (with the approval of the local ethics committee and advisory committee to the NICPR), although the importance of keeping parents informed has always been recognized as good practice. This is similar to the way other disease registries operate in the United Kingdom (eg, cancer registries) but is currently under review by the Department of Health, Social Services and Public Safety Northern Ireland and is likely to lead to a requirement for consent in the near future. However, at the time of recruitment for the Locomotor Study the NICPR was not subject to consent bias, and this offered a unique opportunity to assess the extent to which the sample of children participating was representative of children with cerebral palsy.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Participation in the Locomotor Study involved each child being accompanied by a parent/guardian to attend a hospital-based gait analysis laboratory where a number of physical and psychosocial assessments were undertaken during the course of half a day.
Definitions
Cerebral palsy was defined according to the Surveillance of Cerebral Palsy in Europe Collaborative Group.12 Ambulant cerebral palsy was defined as the ability to walk 10 m, either independently or with the use of an aid (including use of stick(s), crutch(es), or a walking frame). Gross motor abilities were further defined using the Gross Motor Function Classification System (GMFCS).14 The GMFCS includes 5 levels of ability ranging from the most able (level I) to the least (level V). Cerebral palsy subtypes were defined according the Surveillance of Cerebral Palsy in Europe Collaborative Project classification scheme.12 Intellectual impairment was defined as moderate where the intelligence quotient ([IQ] or best clinical estimate) was < 70 50 and severe where the IQ was <50. Visual impairment was defined as moderate where visual acuity was 6/18–6/60 (better eye) and severe/profound where visual acuity was <6/60. Deprivation was defined using the Carstairs Index.15 Children were assigned to a deprivation quintile based on their electoral ward of residence ranging from quintile 1 (least deprived) to quintile 5 (most deprived). Early impairment cerebral palsy was defined as motor impairment secondary to damage sustained to the developing brain before the end of the neonatal period (ie, within the first 28 days of life after birth), and late impairment cerebral palsy was defined as damage known to have occurred sometime after the neonatal period but by the child's fifth birthday.
Sampling Frame
By June 2003, 784 children, alive and resident in Northern Ireland, had been notified to the NICPR. During initial searches, an additional 4 cases unknown previously to NICPR were added to the register and included in the overall sampling frame (n = 788; Table 1). Two of these children have subsequently been notified to NICPR via the normal notification procedure. At this time, 91.1% of children on NICPR had completed follow-up assessments, although 14.1% were completed for <5 years and were unconfirmed cases. These children were included in the sampling frame but were followed up more rigorously to ensure eligibility before being invited to take part.
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A twin track approach to follow-up and recruitment for the Locomotor Study was undertaken. This involved identifying which children with cerebral palsy were also known to the pediatric orthopedic service ([POS] a specialist orthopedic hospital in Greater Belfast) and those known uniquely to NICPR. Overall, 50.9% (401 of 788) of the potentially eligible population was known to both the POS and the NICPR, and 49.1% (387 of 788) was known uniquely to NICPR. Children known to POS were contacted through their child's orthopedic surgeon. Children known only to NICPR were followed up using a community-based network of professionals responsible for notifying the child to NICPR (usually the pediatrician or physiotherapist).
Inclusion Criteria
Children with a diagnosis of ambulant, early impairment cerebral palsy, born June 1, 1987, to June, 1, 1999, alive and resident in Northern Ireland by June 1, 2003, were potentially eligible to take part in the Locomotor Study. Information on ambulatory status and presumed timing of cerebral palsy was available from the NICPR: 20.5% of children were recorded as "no independent walking" with or without the use of aids, and 6.2% were known to have late impairment cerebral palsy. However, a double check involving chart review was undertaken on the eligibility of all of the cases.
Exclusions
Children who did not meet the inclusion criteria were excluded from the Locomotor Study on the basis of a consensus among the research team, the child's clinician or physiotherapist, and using published guidelines.12,16 On follow-up, 38.2% of children were excluded from the study for various reasons (Table 2).
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Eligible Population
Of the 487 families with eligible children, 481 were written to about the study in either October or March (Table 1). Six families were recruited directly while attending a clinical appointment just before the letters were sent out.
A total of 481 parents were sent a letter and information sheet about the study and were asked for permission to release their details to the research team. Parents were asked to complete a reply slip "opting in" and seeking more contact with the research team or "opting out," requesting not to be contacted about the study again. Just more than half (50.7%) responded to an initial invitation (see Table 1, stage 3). Parents who did not respond to this first contact were sent 1 follow-up postal reminder. Sixty-one (25.7%) of 237 nonresponders replied to 1 postal reminder (12.7% of the total contacted). Ten parents who remained "nonresponders" were coincidentally in contact with the POS in relation to a clinical appointment. During this contact, the families were reminded for a second time about the Locomotor Study, and all agreed to be contacted by the researchers and, ultimately, for their child to be assessed. These cases are subsequently referred to as "nonresponders but seen."
Availability of "Baseline" Data
Comparisons between groups are based on a number of key child characteristics. Data for the eligible population (n = 487) regarding age, gender, deprivation quintile of residence, and Health and Social Services Board of residence (of which there are 4) were available for 100% of potential subjects. Data on GMFCS (a computed version17) were available for 99.6%, cerebral palsy subtype for 99.0%, presence and severity of intellectual impairment for 99.0%, and visual impairment for 99.6%. The proportion of missing data did not vary significantly between recruitment tracks or for other subgroups in the analysis (P > .05).
Ethical Approval
The NICPR has the approval of the Local Ethics Committee of the Queen's University Belfast. The Locomotor Study had the permission of the Local Ethics Committee of the University of Ulster.
Statistical Analysis
Percentages were used with 
2 to test differences in proportions between groups. Where 2-by-2 tables are analyzed, the 2 statistic has been corrected for continuity using Yates correction. Statistical significance was set at the P < .05 level. Ninety-five percent confidence intervals (CIs) have been calculated for differences in proportion using a recommended method (Newcombe)17 for independent samples and are reported for statistically significant findings at the P < .05 level, as derived from the 2 test.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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The remaining analysis refers to the 487 children who were invited to take part.
Characteristics of Children Eligible for Follow-up via POS Versus NICPR
A total of 312 children identified through the POS and 175 through the NICPR were eligible to take part (Table 1, stage 2). Frequencies of the baseline characteristics for these subjects are given in Table 3. The characteristics of the children and families followed up by each recruitment track were compared (Table 3). Significant differences in the baseline characteristics of subjects between the 2 tracks were found in relation to age, area of residence, GMFCS level, cerebral palsy subtype, and the presence of intellectual impairment (P < .05). There were no differences in relation to deprivation of area of residence (P > .05).
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Characteristics of Respondents to First Contact Versus Nonrespondents
The overall response rate was 63.4% at the first contact stage (Table 1, stage 3). This rate varied by recruitment track with more families responding to POS compared with NICPR (14.3% difference in proportion; 95% CI: 5.3%–23.2%). More families contacted via POS responded to the first letter of invitation (9.7% difference; 95% CI: 0.4%–18.7%) and the postal reminder (13.9% difference; 95% CI: 2.6%–24.2%) compared with NICPR.
The child and family characteristics of those responding compared with nonresponders did not differ significantly on any of the key variables (P > .05). Similarly, there were no differences in the characteristics of responders versus nonresponders within each recruitment track, with the exception of age and board of residence, which varied significantly within the NICPR track (P > .05).
Characteristics of Those Agreeing to Contact Versus Those Declining
Of the respondents, 83.6% agreed to contact by the research team, and 16.4% declined after receiving more information about the study (Table 1, stage 4). The proportion of families agreeing to contact did not vary significantly by recruitment track (P > .05) but was slightly higher among NICPR families.
The child and family characteristics of those agreeing to contact by the study group were compared with those opting out at this stage. There were no significant differences in any of the baseline characteristics between these 2 groups and no significant differences in the characteristics of those agreeing to contact versus those declining contact within recruitment track (P > .05).
Characteristics of Those Consenting to the Study Versus Those Refusing
Of those agreeing to contact, 65.9% gave consent for their child to participate in the study, and 34.1% declined after receiving further information about the study (Table 1, stage 5). Almost the same proportion of families in both recruitment tracks consented to take part.
The child and family characteristics of those consenting to the study were compared with those refusing at this stage, and no significant differences were found (P > .05). Similarly, there were no significant differences in the characteristics of consenters and nonconsenters within each of the recruitment tracks (P > .05).
Characteristics of Participants in the Study Versus Those Eligible Nonparticipants
A total of 35.7% (174 of 487) eligible children were successfully recruited to the Locomotor Study (Table 1, stage 6), and the rate of participation did not vary significantly by recruitment track (P > .05). The proportion of children included in the study rose to 37.8% (184 of 487) when the 10 nonresponders but seen were added to the overall numbers: 41.3% of children from POS versus 31.4% from NICPR (9.9% difference in proportion; 95% CI: 0.9%–18.4%) participated in the study.
The child and family characteristics of the subjects assessed were compared with those eligible to take part but not assessed: both the characteristics of 174 subjects (minus the 10 nonresponders but seen) versus the remaining population and 184 subjects versus the remaining population were checked in the analyses. There were no significant differences between these 2 comparisons for all of the baseline variables reported (P > .05 respectively). Furthermore, there were no significant differences between these 2 comparisons within each of the recruitment tracks (P > .05, respectively).
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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This analysis suggests that identifying children with cerebral palsy through a specialist service, like orthopedics, for research purposes is likely to lead to incomplete and biased recruitment of children with the condition. It should be noted that the POS is an important source of notification to the NICPR, notifying 37% of all of the cerebral palsy cases.18 Using the NICPR for comparison, the POS tended to know of clinically and demographically different children with cerebral palsy. This pattern is likely to reflect appropriate referrals and a match between clinical services and those most likely to benefit from the service. However, for research purposes, a population-based sampling frame, like a case register, provided it is complete and unbiased in its ascertainment, offers considerable methodologic advantage in recruitment of a representative sample over clinic-based populations.
In terms of initial follow-up, the POS track proved more effective and had a higher response rate to the first invitation and subsequent postal reminder. Ultimately, the POS had better access to the potential study population through clinical contact, and this possibly contributed to a higher proportion of eligible children from POS participating in the study compared with the NICPR. It should be noted, however, that POS recruited an additional 10 children in a different manner from the remaining subjects. Families may have been more familiar with the POS and their child's orthopedic consultant than was apparent through a general community pediatric network contacting families on behalf of NICPR. It also possible that an invitation from an orthopedic surgeon to participate in orthopedic-related research may have had more relevance to parents and been positively influential in their decision-making about participating in the study.
Children followed up via NICPR were socially more complex where a diagnosis, parental acceptance, or family well-being was more uncertain. It is noteworthy that 16 families followed up via NICPR were never approached about the study at the request of community professionals (for the reasons give above), and this strand was more subject to "gatekeeping."10 Furthermore, the NICPR strand included more children subsequently found not to have cerebral palsy, because it tends to be more inclusive than exclusive in provisionally registering young children who can outgrow early signs of motor impairment.19 These children are subsequently removed from the register.
This study provides evidence that 1 reminder follow-up of families increases the response rate by >10% and is worth doing. Problems with ethical committees advising against follow-up have been reported, and failure to follow up with reminders could potentially weaken the scientific merit of the research.4 Moreover, 2 reminders was even more effective (although based on small numbers). Nonresponse is more likely to reflect patchy cooperation by professionals facilitating contact with families than families refusing or objecting to taking part.11 The NICPR track was more vulnerable to this than the POS track, which achieved a significantly higher response rate. It is possible that families who feel strongly about refusing are more likely to respond to an invitation provided they are given the opportunity to opt out. In this study, 28% (137 of 481) of families approached either refused contact with the research team or declined to take part in the study. Although this is much higher than rates reported for noncontact epidemiologic research in children with cerebral palsy (<2%),20 this study involved a battery of clinical assessments requiring considerable commitment by the child and parents. Despite this comparatively high refusal rate, this did not affect the integrity of this clinical project.
Our approach to recruitment enabled us to ascertain that we actually captured 38% of the total eligible population in a geographically defined area. Although this proportion is lower than we had hoped for, there was no evidence that the participants were biased on a number of key child and family characteristics, and this finding is similar to another report using an epidemiologic approach to identifying children with hemiplegia.11 Few research studies have been able to establish this in the same systematic way, and unlike other studies, we do not report systematic differences in the characteristics of children participating in research at various stages of recruitment. However, unlike many other analyses of bias, we started off with a highly ascertained record of every eligible child resident in a geographically defined area as a result of years of separate, funded data collection. In the United Kingdom, recent concerns about the requirements for consent for health surveillance and the compilation of disease registries21–23 means that it will become more difficult to conduct unbiased population-based research and, indeed, carry out the type of analysis reported in this article.
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CONCLUSIONS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONSREFERENCES |
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Care must be taken in the recruitment of research subjects to ensure that samples are adequately representative. This phase of a research project is time consuming and usually underreported in the literature. A recruitment rate of 38% could be devastating to an epidemiologic study of risk factors or trends in prevalence but not necessarily to clinical research provided that subjects are not biased by the clinical attribute under investigation. Researchers need to consider in advance how they will obtain a representative series of subjects more inclusive than clinic-based populations, the extent to which they will depend on other professionals to facilitate recruitment of those subjects, and how they will assess nonresponse and nonparticipant bias in their study population. Giving potential subjects the choice of opting out is at least one way of capturing data about refusal rates as opposing to "losing" subjects to nonresponse.
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ACKNOWLEDGMENTS |
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This study was supported by the Northern Ireland Research and Development Office for the financial support of the Locomotor Study (project grant RSG/1708/01) and the Department of Health, Social Services, and Public Safety Northern Ireland for funding the Northern Ireland Cerebral Palsy Register.
We thank the children and parents who have so willingly taken part in the Register and Locomotor Study. We also thank Dr Nan Hill, Consultant Pediatrician, South and East Belfast Trust and Clinical Advisor to Northern Ireland Cerebral Palsy Register, for her validation work on the register.
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FOOTNOTES |
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Accepted May 23, 2006.
Address correspondence to Jackie Parkes, BNurs, PhD, Queen's University Belfast, Room 1.36, Mulhouse Building, Grosvenor Rd, Belfast, BT12 6BJ Ireland. E-mail: j.parkes{at}qub.ac.uk
The authors have indicated they have no financial relationships relevant to this article to disclose.
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