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Evidence for Changing Guidelines for Routine Screening for Retinopathy of Prematurity
Shoo K. Lee, MBBS, FRCPC, PhD;
Charles Normand, BA, DPhil;
Douglas McMillan, MD, FRCPC;
Arne Ohlsson, MD, FRCPC, MSc;
Michael Vincer, MD, FRCPC;
Christopher Lyons, MBBS, FRCSC;
for the Canadian Neonatal Network
Arch Pediatr Adolesc Med. 2001;155:387-395.
ABSTRACT
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Context Existing guidelines recommended by the Canadian Pediatric Society (CPS)
and American Academy of Pediatrics (AAP) for routine screening for retinopathy
of prematurity (ROP) remain controversial.
Objective To determine whether current guidelines for routine screening for ROP
should be changed.
Design We examined data that were collected as part of a larger study of 14
neonatal intensive care units (NICUs) in Canada. We examined the effect of
strategies using different birth weight (BW) and gestational age (GA) criteria
for routine ROP screening, and performed a cost-effectiveness analysis.
Setting The 14 NICUs (except one) are regional tertiary level referral centres
serving geographic regions of Canada, and include approximately 60% of all
tertiary-level NICU beds in Canada.
Patients This large cohort included all 16 424 infants admitted to 14 Canadian
NICUs from January 8, 1996, to October 31, 1997.
Interventions None.
Main Outcome Measure Treatment for ROP.
Results The most cost-effective strategy was to routinely screen only infants
having a BW of 1200 g or less. This included all infants treated for ROP (except
1 outlier at 32 weeks GA and 1785 g BW), at a marginal cost per additional
person with improved vision of $513 081 for screening patients between
28 weeks GA and 1200 g BW, compared with $1 800 039 and $2 075 874
for using the current AAP and CPS guidelines, respectively (cryotherapy outcomes).
Results for laser therapy were similar, but costs were slightly lower. This
strategy reduced the number of infants screened under the current CPS guidelines
by 46%.
Conclusion Screening only infants having a BW of 1200 g or less is the most cost-effective
strategy for routine ROP screening.
INTRODUCTION
ROUTINE SCREENING of preterm infants for retinopathy of prematurity
(ROP) is now recommended in many countries. Guidelines published by the Canadian
Paediatric Society (CPS) in 19981 recommended
routine screening for ROP in all infants at or younger than 30 weeks gestational
age (GA) or with 1500 g or lower birth weight (BW). Meanwhile, in 1997, those
from the American Academy of Pediatrics (AAP)2
recommended routine screening for all infants younger than 28 weeks GA or
with lower than 1500 g BW, as well as those infants with a BW at or above
1500 g with an unstable clinical course felt to be at risk by the attending
physician. Previous authors3, 4, 5
have found treatment with either cryotherapy or laser therapy to be effective
in reducing the incidence of poor ophthalmic outcomes, and routine screening
and treatment for ROP to be cost-effective.6
However, since screening for ROP requires specialized skills and equipment,
has potentially harmful effects on the infant, and carries an associated cost,
the appropriateness of current criteria for routine screening has been recently
questioned.7, 8, 9
Hussain et al8 reported that the incidence
and severity of ROP have decreased significantly in the present era of surfactant
therapy, and that no infant born after 28 weeks GA or having a BW greater
than 1000 g required retinal surgery in a cohort of 2528 infants. Wright et
al9 similarly found no cases of threshold ROP
or stage 4 ROP10 among infants of a greater
than 1200 g BW in a cohort of 707 infants. Goble7
examined 1611 infants from 6 neonatal intensive care units (NICUs) in the
United Kingdom and found that limiting routine screening of ROP to infants
born before 29 weeks GA or with a BW at or below 1250 g did not reduce detection
of severe ROP ( stage 3 ROP)10 or detection
of those requiring treatment. However, since these studies involved small
sample sizes, larger and more definitive population-based evidence is needed.
The purpose of this study is to examine recent data from a large cohort of
Canadian infants to determine whether there is evidence to support changing
the present guidelines for routine screening for ROP.
PATIENTS AND METHODS
STUDY POPULATION
The study population comprised all 16 424 infants admitted to 14
NICUs in the Canadian Neonatal Network11, 12
during a 22-month period from January 8, 1996, to October 31, 1997. The 14
hospitals (except one) are regional tertiary-level referral centers and include
about 60% of all tertiary-level NICU beds in Canada (Table 1). Each NICU served a distinct geographic region and coordinated
infant transfer and care within the region. Infants moved out of their region
only for specific care that could not be provided by the regional hospital,
or if excess patient census prevented admission to the regional hospital.
In the latter event, patients were usually transferred back to the regional
hospital as soon as patient census permitted. There were 267 NICU beds total
(range, 2-45 beds) and 262 intermediate-level and continuing care beds (range,
0-45 beds) among the 14 NICUs. The mean number of annual admissions to a NICU
was 673 (range, 133-1129 admissions). Cryotherapy and laser therapy for ROP
were available in 8 hospitals. At the other 6 hospitals, infants were transferred
to other hospitals for treatment of ROP. The data were collected as part of
a larger study of practices and outcomes of NICUs12
across Canada, which had a population of nearly 30 million people13 and more than 357 000 births14
in 1996. The 14 NICUs in this study served a population of about 18 million
people.
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Table 1. Inclusion Criteria for Routine ROP Screening in 1996 and 2000*
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DATA ABSTRACTION
Trained research assistants prospectively abstracted patient information
from the mothers' and infants' medical records at each hospital on a daily
basis. Data were directly entered into laptop computers using a customized
data entry program with built-in error checking and a standard manual of operations
and definitions.15 Data were electronically
transmitted to the Canadian Neonatal Network Coordinating Center at the British
Columbia Research Institute for Children's and Women's Health, Vancouver,
British Columbia, for verification. Potential data errors were rechecked by
site research assistants. Data management was conducted by the Canadian Neonatal
Network Coordinating Center, in concert with a Steering Committee composed
of experienced researchers and neonatologists representing each of the 5 geographic
regions (British Columbia, Prairie Provinces, Ontario, Quebec, Maritime Provinces)
in Canada, and with site investigators representing each of the participating
hospitals. Patient information was collected until death or until discharge
from the NICU. For patients transferred to a community hospital prior to discharge
home, written recommendations for ROP screening accompanied the patients on
transfer, and ROP screenings were performed at the community hospitals. In
Canada, ROP treatment is only performed at tertiary-level referral hospitals.
All patients diagnosed with threshold ROP at community hospitals were transferred
to a regional tertiary-level hospital for treatment. To ensure inclusion of
patients referred from community hospitals for ROP treatment, we identified
all patients treated for ROP in regional tertiary-level hospitals (including
the NICU, pediatric intensive care unit, operating theater, and general pediatric
wards) located in the geographic regions included in the study during the
study period between 1996 and 1997 and for 1 year subsequently, and matched
them against subjects in our study.
PATIENT INFORMATION AND VARIABLE DEFINITIONS
Patient information included information on ROP (stage, zone, and treatment
given)10 and treatment for ROP. Institutional
criteria for routine screening for ROP in 1996 and 1999 were obtained from
each institution. Study variables were defined according to the Canadian Neonatal
Network SNAP Project Abstractor Manual.15 Gestational
age was defined as the best obstetric estimate based on early prenatal ultrasound,
obstetric examination, and obstetric history unless the postnatal pediatric
estimate of gestation differed from the obstetric estimate by more than 2
weeks. In that case, the pediatric estimate of GA based on the best estimate
of the attending neonatologist or the Ballard Score16
was used instead. Survival was defined as survival to discharge home from
the NICU or from another hospital to which the patient had been transferred.
Retinopathy of prematurity was defined according to the International Classification
for Retinopathy of Prematurity10 and the Reese
Classification17 of cicatrical disease.
OUTCOME DEFINITION
We chose treatment for ROP (ie, "threshold" disease) as the primary
outcome. The currently accepted indication for treatment is "threshold" disease
(ie, stage 3 ROP extending for longer than at least 5 contiguous clock hours
or at least 8 cumulative clock hours in zone I or zone II, with plus disease).
At this stage, the risk of blindness is around 50%, and treatment of threshold
disease using cryotherapy has been shown to reduce unfavorable outcome (visual
acuity worse than 20/200 OU) from 61.7% to 47.1% at 5 years of age.5 More recently, laser therapy has been reported to
improve visual outcomes by 10% to 50% when compared with cryotherapy.18, 19, 20, 21 Many
previous studies used severe ROP ( stage 3 ROP) as the end point.1, 3, 6 However, not all patients
with stage 3 disease require treatment, and evidence from the Multicenter
Trial of Cryotherapy for ROP5 suggests that
treatment for ROP that does not reach threshold may have the adverse effect
of reducing the prospect for normal vision. We also examined cost-effectiveness
of screening and treatment for ROP.
DATA ANALYSIS
We examined the implications of 3 different strategies for routine screening
for ROP using (1) GA criteria, (2) BW criteria, and (3) combined GA-BW criteria.
For each strategy, we chose a range of criteria to ensure inclusion of all
infants treated for ROP. Since the most mature and largest infant treated
for ROP in the study cohort was born at 32 weeks GA, with a 1785 g BW, we
examined GA criteria up to 32 weeks, BW criteria up to 1800 g, and combined
GA-BW criteria up to 32 weeks GA or 1800 g BW. We cross-tabulated the number
of infants who were screened, who had higher than stage 3 ROP, and who were
treated for ROP against the GA, BW, and combined GA-BW criteria (Table 2). We used the table to identify
the criterion that included all infants treated for ROP but screened the least
number of infants.
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Table 2. Implications Using Different Screening Criteria*
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ASSUMPTIONS FOR COST-EFFECTIVENESS ANALYSIS
Cost-effectiveness analysis was undertaken from the viewpoint of the
provincial payer. Canada has a tax-funded universal health insurance system
that pays physicians according to a set schedule of fees. Hospitals are given
a global budget. Patients do not pay out of pocket for health care. Therefore,
costs relevant to the health care system are the provincial payer reimbursement
schedule and the allocated hospital costs. Charges and other payments are
not available or relevant. Table 3
shows the cost inputs used in the calculations. Costs of screening were estimated
by applying the British Columbia provincial payer reimbursement schedule22 to screening guidelines published by Schalij-Delfosetel23 and recommended by the CPS.1
Under this guideline, screening was first performed at 32 weeks corrected
GA, and then at 2 weekly intervals until 40 weeks GA. A screening test fee
of $117.84 was paid for each eye examination. For infants screened and found
to have stage 3 or higher ROP, we assumed that screening was subsequently
conducted at weekly intervals until 40 weeks corrected GA or until treatment.
A consultation fee of $64.70 was paid when an infant was referred for ROP
treatment. A treatment fee of $464.72, which includes postsurgery examinations,
was paid for each eye treatment performed. Data from the Cryotherapy for Threshold
ROP Trial6 showed that 27.5% of eye treatments
were administered using general anesthesia, so we factored in an anesthesia
fee (a $64.01 consultation fee plus a $212.80 anesthesia fee) for 27.5% of
treatments. Costs of hospital treatment were estimated using hospital accounts
data based on the number of tests and treatments carried out. This included
an operating theater fee of $400 for each operation, one additional night
of NICU stay ($709.41) if the patient was readmitted for surgery, and a laser
therapy equipment depreciation charge of $617.74 per eye treated (based on
initial equipment cost of $80 000, straight-line amortization throughout
10 years, discount rate of 5%, zero salvage value, and one-third usage by
patients other than infants requiring treatment for ROP, which is the norm
at the Children's and Women's Health Centre of British Columbia). For readmitted
infants, the cost of transfer by air and by land were obtained from the British
Columbia Ambulance Service (S.K.L., unpublished data, 1996). For infants receiving
treatment before being discharged from the hospital providing the intensive
care, we assumed that no additional hospital stay was incurred. Costs to hospitals
that may have delayed transfer to less costly level I or level II nurseries
because of ROP screening were not included. Costs to parents were not considered.
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Table 3. Cost Inputs and Cost Calculations*
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The estimates of outcome in terms of poor ophthalmic outcomes avoided
were obtained from recent data on efficacy of treatment published by the Multicenter
Trial of Cryotherapy for ROP5 and from review
of recent publications comparing laser treatment with cryotherapy, which suggested
that laser treatment may improve visual outcomes by 10% to 50% compared with
cryotherapy.18, 19, 20, 21
We assumed that symmetric eye disease occurred in 82.5% of patients, as reported
by Palmer et al,24 and retreatment was required
in 6.4%.6
For each of the 3 screening strategies (GA, BW, and combined GA-BW)
considered, we derived a total cost of screening and treatment using each
criteria (Table 3). Using data
from the Multicenter Trial of Cryotherapy for ROP,5
which showed a reduction in unfavourable visual acuity outcomes from 61% to
47%, we estimated the number of persons with improved vision as a result of
surgery, and the average cost per person with improved vision. We assumed
that laser treatment would improve cryotherapy outcomes by between 10% and
50%, and we estimated costs associated with these outcomes. With progressive
moves from one screening criterion to the next screening criterion (eg, moving
from screening only infants at  26 weeks GA to screening all infants 27
weeks GA, and so on), we also estimated the number of additional persons with
improved vision and the marginal cost per additional person with improved
vision (MC/APIV).
Sensitivity analysis was conducted using 2 scenarios: (1) all eligible
infants were screened, additional cases of stage 3 or higher ROP and treatment
for ROP were detected in the same proportions by GA and BW, as infants who
received screening in the study cohort; (2) infants with a 1200 g or lower
BW were screened as per Scholij-Delfosetel's criteria,23
plus infants between 1200 g and 1800 g BW were screened once only at 37 weeks
gestation. This is a low-cost strategy designed to capture the outlier (largest
treated infant in the cohort).
RESULTS
In 1996, 13 different criteria were used by the 14 hospitals in the
study (Table 1). In 2000, only
4 hospitals had adopted the CPS guidelines1
published in 1998. Of the 16 424 infants in the study, 2077 were screened
in the NICU prior to discharge or transfer. Under the CPS guidelines,1 3408 live-born infants would have been eligible for
screening, but only 1939 of these infants were screened prior to discharge
or transfer from the NICU. Of the remaining 1469 infants, 386 died in the
NICU, 409 were discharged home without screening, and 674 were transferred
to another hospital prior to discharge home. Table 2 presents the results of screening and treatment given, stratified
by GA, BW, and a combination of GA-BW. One treated infant, who was born at
32 weeks and 1785 g, was an outlier who would not have been eligible for screening
under existing CPS1 and AAP2
guidelines. However, screening was requested by the attending neonatologist
for this infant because of an extremely difficult clinical course with a prolonged
period of exposure to high oxygen concentrations. Since this infant had risk
factors that were different from the usual for ROP, we analyzed the data both
excluding and including this infant.
Table 2 presents the most
efficient screening strategy to include all infants treated for ROP (excluding
the outlier infant): to screen only infants with a BW of 1200 g or lower.
This requires the screening of 1631 eligible infants in the study cohort.
The CPS1 and AAP2
recommendations would have required the screening of 3022 and 2733 eligible
infants respectively, without additional benefit. If the outlier infant was
included in the analysis, the most efficient screening strategy to include
all infants treated for ROP is to screen only infants with a 1800 g or lower
BW (requires screening of 3980 eligible infants).
Table 4, Table 5, and Table 6
summarize the costs of using different screening criteria in the NICU, arranged
by ascending order of persons with improved vision. Screening criteria that
produce equivalent (or worse) outcomes at higher cost are considered "dominated"
and are excluded from the table or indicated as "dominated" in the table.
In cost-effectiveness analysis, the critical consideration is the additional
cost of a unit of improved outcome at the margin (MC/APIV). For instance,
as presented in Table 4, Table 5, and Table 6, for cryotherapy outcomes in the observed cohort, the MC/APIV
in shifting from screening infants born at 700 g or less BW to screening infants
born at 26 weeks or earlier is $53 354. Shifting from screening infants
born at 26 weeks or earlier to infants born at 27 weeks or earlier results
in a lower MC/APIV ($179 476) than shifting to screening infants born
with a 1 kg or lower BW (MC/APIV, $314 269). Therefore, screening infants
born at 27 weeks or earlier dominates screening infants born with a 1 kg or
lower BW.
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Table 4. Summary Costs of Progressive Screening and Treatment of Observed
Cohort in NICUs and Community Hospitals*
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Table 5. Sensitivity Analysis of All Eligible Infants Screened, With
Additional Stage 3+ and Treated Patients in Proportion to Screened Cohort*
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Table 6. Sensitivity Analysis of Infants Below Cutoff Criteria Who
Were Screened as per Regular Schedule and Infants Between Cutoff Criteria
and 1800 g Who Were Screened Only Once*
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A clear pattern emerges from Table
4, Table 5, and Table 6. If the outlier infant is excluded,
the strategy to screen only infants with a 1200 g or lower BW dominates all
other strategies capable of capturing all infants treated for ROP. No additional
benefit is derived from screening infants with a greater than 1200 g BW. It
is possible to achieve the same outcome using a combined GA of 28 weeks or
less and a BW of 1200 g or less as the screening criteria, but this provides
no improvement in either detection or cost-effectiveness (the MC/APIV for
shifting from screening infants with a 28-week GA to a combined GA 28
wk/BW 1200 g screening criteria is $789 521, compared with $513 081
for shifting to the BW 1200 g criterion). The AAP2
and CPS1 guidelines provide no additional benefit
as compared with the criterion we used (BW 1200 g), and cost significantly
more (MC/APIV, $1 800 039 for AAP criteria and $2 075 874
for CPS criteria). Finally, moving to a criterion of a BW of 1800 g or less,
from a BW of 1200 g or less, captures the outlier infant, but at a MC/APIV
of $3 407 425.
The results are similar for laser therapy, but the costs are lower using
the assumptions that laser therapy results in a 10% to 50% improvement in
visual outcomes compared with cryotherapy. The criterion using a BW of 1200
g or less dominates all other screening strategies. Moving from screening
infants with a GA of 28 weeks or less GA to screening infants with a 1200
g or lower BW results in a MC/APIV that ranges from $214 028 (50% improvement
in visual outcomes) to $416 166 (10% improvement in visual outcomes).
The cost is significantly higher for the AAP criteria (equivalent MC/APIV
range, $750 874-$1 460 032) and the CPS criteria (equivalent
MC/APIV range, $865 936-$1 683 764), with no increase in benefit.
Shifting criteria (from 1200 g BW to 1800 g BW) captures the outlier
infant, but at a significantly higher cost (equivalent MC/APIV range, $1 421 383-$2 763 801).
Given the small numbers of cases in total, it is important not to interpret
the differences too broadly, but using a BW limit of 1200 g would achieve
the maximum health gain at the lowest cost. Most of the gain is achieved using
a much lower threshold, such as 26 weeks GA. Screening very preterm and low-birth-weight
infants provides benefits at modest costs. Moving to include all infants who
are likely to benefit achieves its gains at a much higher cost. The analysis
shows that there was no advantage in using screening criteria that combine
both GA and BW, since BW alone is more cost-effective.
SENSITIVITY ANALYSIS
The data from this study confirm that, at least for some infants, screening
and follow-up observation or treatment is likely to be cost-effective, and
that the policy issue is whom the program should cover. Since some infants
were not screened because of differences in screening criteria among NICUs,
it is worth looking at the sensitivity to the assumptions if the costs of
screening all eligible infants are included in the analysis. It is also worth
looking at the sensitivity to the assumptions if infants having a BW between
1200 g and 1800 g are screened only once at 37 weeks GA. This low-cost strategy
minimizes screening of larger infants with low risk of ROP, but permits inclusion
of the outlier infant.
ASSUME ALL ELIGIBLE INFANTS HAVE BEEN SCREENED
Additional stage 3 cases and treated cases among unscreened infants
occur in the same proportion as for screened infants. Our estimates of costs
from the observed study cohort underestimate the actual costs because screening
criteria of some hospitals excluded larger infants with low risk of ROP. A
more realistic estimate of the relative cost-effectiveness of different screening
strategies would assume that all eligible infants are screened, and that additional
cases of a stage 3 or greater ROP and treatment for ROP among unscreened infants
occurred in the same proportion as for screened infants of equivalent BW and
GA. The only exceptions are infants who may have moved out of the study regions
within 1 year of birth and thus escaped inclusion in the results. This scenario
does not change the relative cost-effectiveness of the different screening
strategies, but the MC/APIV of screening infants at 28 weeks GA and with 1200
g BW is $479 895 for cryotherapy (range, $200 185-$389 248
for laser therapy, corresponding with a 50%-10% improvement in visual outcomes).
Shifting to the AAP2 criteria (MC/APIV for
cryotherapy, $2 195 771; MC/APIV range for laser therapy, $915 950-$1 781 015)
or the CPS criteria (MC/APIV for cryotherapy, $2 663 120; MC/APIV
range for laser therapy, $1 110 902-$2 160 086) costs
significantly more with no additional benefit. Shifting from screening infants
born at a BW of 1200 g or lower, to screening infants born at a BW of 1800
g or lower would include the outlier infant, but at a MC/APIV of $7 083 998
for cryotherapy (range, $2 955 039-$5 745 909 for laser
therapy). This strategy dominates using a GA criterion of 32 weeks or lower
or a combined GA/BW criteria of 28 weeks GA and 1800 g BW (MC/APIV, $7 791 499
and $7 120 791, respectively, for cryotherapy, and slightly less
for laser therapy).
COST-SAVING MEASURE
As a cost-saving measure, a regular screening schedule for all infants
below cutoff criteria was produced; once-only screening at 37 weeks GA for
infants from cutoff criteria, to 1800 g BW. This strategy permits inclusion
of the outlier infant, but saves costs by minimizing the frequency of eye
examinations for low-risk infants between a cutoff criteria and 1800 g BW.
The dominant cutoff criterion is 1200 g BW for regular screening of infants.
The MC/APIV for shifting from a cutoff criterion of 28 week or lower GA to
1200 g or less BW is $354 441 for cryotherapy, and this cost ranges from
$147 852 to $287 491 for laser therapy. Adopting the AAP and CPS
criteria as cutoffs increases costs with no additional benefit. All other
strategies are dominated. For comparison, the MC/APIV for shifting from screening
only infants with 1200 g or lower BW (ie, no screening for infants >1200 g
BW) to this strategy (regular screening schedule for infants 1200 g BW,
plus once-only screening for infants with a BW of 1201 g to 1800 g) is $1 889 159
for cryotherapy, and ranges from $788 049 to $1 532 318 for
laser therapy.
COMMENT
Our findings are highly relevant because they are current, and they
are derived from almost 2 years of data from a large cohort of infants in
the Canadian Neonatal Network, representing about 60% of the NICU admission,
from a population of 30 million in Canada in 1996. We found significant variation
in criteria used by different Canadian hospitals for routine screening for
ROP (Table 1), even after publication
of national guidelines by the CPS1 in 1998.
Reasons given for this variation include limitation of resources, lack of
available qualified ophthalmologists, and disagreement with the current CPS
recommendations. Differences in screening criteria raise a number of contentious
issues, including medicolegal questions arising from noncompliance with nationally
accepted guidelines. Disagreement about appropriate criteria for routine screening
for ROP is not restricted to Canada. The AAP2
in the United States and Goble et al7 in the
United Kingdom have advocated different guidelines than those recommended
by the CPS in Canada. Clarification of appropriate screening criteria is urgently
needed, both for patient management and medicolegal reasons.
GUIDELINES BENEFITS
Guidelines serve to guide physicians in important or contentious issues,
and offer reassurance to physicians and to the public that individual physician
practices conform to accepted best practice. Guidelines are consensus statements
developed by groups of physicians and are based on expert opinion and review
of the existing literature. Consequently, the relevance and quality of guidelines
depend heavily on the quality of existing literature. The CPS guidelines on
routine screening for ROP were developed after an extensive review of the
literature.3 However, most of the studies reviewed
were of small sample size (the 7 population-based studies24, 25, 26, 27, 28, 29, 30, 31
ranged from n = 117 to n = 505), and only 1 study was Canadian in origin.24 Four of these studies24, 25, 26, 27, 28
were from a much earlier era (1984-1990) and may have limited applicability
to current practices and outcomes. Indeed, there is evidence that the incidence
of severe ROP has declined in recent years. Kennedy et al32
reported a 50% decrease in the incidence of severe ROP in the postsurfactant
era compared with the presurfactant era. More recently, Hussain et al,8 Wright et al,9 and
Goble et al7 have questioned whether we are
screening too many preterm infants because of declining incidence and severity
of ROP. Consequently, current information derived from large cohorts such
as the Canadian NICU Network11, 12
are highly informative.
An important consideration is whether screening criteria should include
all infants requiring treatment for ROP or whether outliers with exceptional
circumstances should be excluded. In the study cohort, the outlier-treated
infant clearly lies outside current screening criteria established by both
the CPS1 and AAP2
guidelines. Other authors7, 33
have reported similar cases of outlier infants requiring treatment for ROP.
Our data show that using a screening criteria that captures the outlier infant
(ie, screen all infants with a BW 1800 g) would increase the number of
eligible infants requiring screening by 144% (from 1631 to 3980 infants),
and result in a MC/APIV ranging from $1 421 383 to $7 083 998
for screening all eligible infants with BWs between 1200 g and 1800 g. Total
costs of screening and treatment would rise between 45% and 94% each year.
Consequently, the most cost-effective strategy is to routinely screen only
infants with a 1200 g or lower BW. Infants with a greater than 1200 g BW and
with an unstable clinical course should be screened at the discretion of the
attending physician.
Examination of the published literature lends support to this approach.
The CPS3 review of the literature found that
only 1 study (Fledelius28) reported surviving
infants with a higher than stage 3 ROP (3/287 infants or a 1% incidence) among
infants at 1500 g BW. Six other reports24, 25, 26, 27, 29, 30, 31
did not find any infants with stage 3 or higher ROP in infants having a 1500
g or higher BW. There were no cases of stage 3 or higher ROP, or blindness
among infants with a BW 1200 g or greater in 3 of the 5 studies (Darlow,27 n = 169; Barnekow and Stigmar,30
n = 132; Haugen and Markestad,31 n = 207).
Data from the remaining 2 studies (Ng et al26
and Holmstrom et al29) did not reveal whether
there were any cases of stage 3 or higher ROP, or blindness among infants
with a BW of 1200 g or higher. It is noteworthy that Fledelius'28
data were from an earlier period (1981-1988) than those of the other 6 studies
(1985-1993), and may reflect clinical practices from a different era. More
recently, Keith and Doyle33 reported 2 cases
(BW 1.29 kg/33-wk GA and BW 1.43 kg/32-wk GA) from Australia, and Goble et
al7 reported 1 case (BW 1.37 kg/29-wk GA) from
the UK of stage 3 or greater ROP among infants with a 1200 g or lower BW.
It was not possible to discern from the reports whether any of these infants
required treatment for ROP. Goble et al7 recommended
ROP screening for all infants with a BW 1250 g or lower or a GA 29 weeks or
earlier. Our results are in agreement with Goble's findings that it is possible
to screen fewer infants without a loss of detection of cases requiring treatment
for ROP, but we are at variance with Goble's findings in that we found that
the BW criteria dominated both the GA criteria and the combined GA-BW criteria.
As compared with the CPS guidelines, our findings show that a strategy
of screening all infants with a 1200 g or lower BW reduces the number of infants
requiring screening by 46% annually. This translates into savings on screening
costs to the provincial payer of more than $1 million annually in Canada.
In addition, 46% fewer infants will be exposed to the risks (including adverse
effects of mydiatrics, apnoea, tachycardia, hypoxia, aspiration, and need
for reintubation and mechanical ventilation) and discomfort associated with
the screening procedure itself.
An alternative strategy of routine screening for all infants with a
1200 g or lower BW, plus once-only screening (at 37 wk GA) for infants having
a BW between 1200 g and 1800 g, is a low-cost strategy that attempts to include
all potential outlier infants with a BW up to 1800 g. This strategy reduces
the cost of screening infants with a BW between 1200 g and 1800 g, but the
MC/APIV of shifting from screening only infants with a BW 1200 g or lower
to this strategy still ranges from $778 049 to $1 889 159.
We did not have data to infer whether this strategy is more or less effective
at including high-risk outlier infants in a reliable and timely manner than
simply relying on clinician judgement to selectively screen infants with a
greater than 1200 g BW who are at high risk because of unstable clinical course.
LIMITATIONS OF STUDY
A limitation of this study is the lack of complete screening information
on all infants with a 1800 g or lower BW. Therefore, we assumed (in the sensitivity
analysis) that the number of infants with stage 3 or higher ROP and treatment
cases among unscreened infants occurred in the same proportion as those among
screened cases for the same BW and GA groups. This did not alter the relative
cost-effectiveness of the different screening strategies. Another limitation
is that we did not include costs of delayed transfer to less costly level
I or level II nurseries. Some infants may have slightly fewer than the number
of eye examinations assumed because their retinas may mature earlier. However,
other infants may have slightly more than the number of eye examinations assumed
because they have progressive ROP. A few infants may have relocated away from
the study regions and escaped inclusion in our results. However, since our
study regions included about 60% of the Canadian population and the incidence
of treatment is low, the probability that an infant with threshold ROP escaped
inclusion in our data is low. We did not have data on the incidence of severe
ROP diagnosed at community hospitals, but this did not affect our analysis
since the end point was treatment for ROP and not severe ROP. Another limitation
is the lack of cost data from a societal perspective. We did not estimate
indirect costs, long-term costs, costs to the family, economic consequences
to society, and intangible costs arising from pain and discomfort associated
with the screening procedure, or parental anxiety provoked by screening. However,
our objective was to determine the most cost-effective strategy for routine
screening of ROP, and the perspective of the provincial payor is relevant
in this regard. Since the strategy of screening all infants having a 1200
g or lower BW dominates all other strategies; a cost-benefit analysis using
a societal perspective is likely to yield the same result. While these limitations
may affect our estimates of costs slightly, they neither change the relative
cost-effectiveness of the screening strategies nor alter the central findings
of this study.
CONCLUSIONS
It is important to continue to monitor the effects of screening on the
cases detected and on treatment provided. Since some diversity is likely to
continue, the advantages (if any) of more frequent screening or more inclusive
criteria can be monitored. However, on the basis of the best available evidence
on the comparative cost-effectiveness of different screening strategies, BW
seems to be a better criterion than GA. Routine screening is unlikely to be
justified for infants with a BW greater than 1200 g.
AUTHOR INFORMATION
Accepted for publication November 16, 2000.
This study was supported by grants 40503 and 00152 from the Medical
Research Council of Canada, Ottawa, Ontario. Additional funding was provided
by the British Columbia Children's Hospital Foundation Vancouver; the Calgary
Regional Health Authority, Calgary; Dalhousie University Neonatal-Perinatal
Research Fund; the Division of Neonatology, Children's Hospital of Eastern
Ontario, Ottawa; the Child Health Program, Health Care Corporation of St John's,
Newfoundland; the Division of Neonatology, The Hospital for Sick Children,
Toronto, Ontario; Lawson Research Institute, London, Ontario; Midland Walwyn
Capital Inc, Toronto; the Division of Neonatology, McMaster Health Sciences
Centre, Hamilton, Ontario; Mount Sinai Hospital, Toronto; North York General
Hospital Foundation, North York, Ontario; Saint Joseph's Health Centre, University
of Saskatchewan Neonatal Research Fund, London, Ontario; University of Western
Ontario, London; and the Women's College Hospital, Toronto.
Presented at the annual meeting of the Pediatric Academic Societies,
May1-4, 1999, San Francisco, Calif.
Members of the Canadian Neonatal Network
The following are members of the Canadian Neonatal
Network Shoo K. Lee, MBBS, FRCPC, PhD (Canadian Neonatal
Network, Canadian Neonatal Network Coordinating Centre, Vancouver);
Wayne Andrews, MD, FRCPC (Charles A. Janeway Child Health
Centre, St John's); Ranjit Baboolal, MBChB, FRCPC (North York Hospital, North York); Jill Boulton, MD, FRCPC (St Joseph's Health Centre, London; previously at Mt Sinai Hospital, Toronto); David Brabyn, MBChB, FRACP, FRCPC (Royal Columbian
Hospital, New Westminster, British Columbia); David S. C. Lee, MBBS,
FRCPC (St Joseph's Health Centre, London); Derek
Matthew, MRCS, FRCPC, SM (Victoria General Hospital, Victoria,
British Columbia); Douglas D. McMillan, MD, FRCPC (Foothill's Hospital, Calgary); Christine Newman, MD, FRCPC (Hospital for Sick Children, Toronto); Arne Ohlsson, MD, FRCPC, MSc (Mt Sinai Hospital, Toronto; formerly at Women's College Hospital,
Toronto); Abraham Peliowski, MD, FRCPC (Royal Alexandra
Hospital, Edmonton, Alberta); Margaret Pendray, MBBS, FRCPC (Children's & Women's Health Centre of British Columbia, Vancouver);
Sankaran Koravangattu, MBBS, FRCPC (Royal University Hospital,
Saskatoon, Saskatchewan); Barbara Schmidt, MD, FRCPC, MSc (McMaster Health Sciences Centre, Hamilton); Mary Seshia, MBChB, FRCP(Ed),
FRCPC (Health Sciences Centre, Winnipeg, Manitoba);
Anne Synnes, MDCM, FRCPC, MHSc (Children's and Women's Health
Centre of British Columbia, Vancouver; formerly at Montreal Children's Hospital,
Montreal, Quebec); Paul Thiessen, MD, FRCPC (Children's
& Women's Health Centre of British Columbia, Vancouver); Robin
Walker, MBBS, FRCPC (Children's Hospital of Eastern Ontario
and Ottawa General Hospital, Ottawa); and Robin Whyte, MBBS, FRCPC (IWK-Grace Health Centre for Women, Children and Families, Halifax).
The following are members of the Canadian Neonatal Network Coordinating Centre,
Vancouver: Li-Yin Chien, MPH, ScD; Joanna Sale, MSc; Herbert Chan,
MSc; and Shawn Stewart, BA.
From the Department of Pediatrics, University of British Columbia,
and the Centre for Community Health and Health Evaluation Research,Vancouver,
British Columbia (Dr Lee); the London School of Hygiene and Tropical Medicine,
London, England (Dr Normand); the Department of Pediatrics, University of
Calgary, Alberta (Dr McMillan); the Department of Pediatrics, University of
Toronto, Ontario (Dr Ohlsson); the Department of Pediatrics, Dalhousie University,
Halifax, Nova Scotia (Dr Vincer); and the Department of Ophthalmology, University
of British Columbia (Dr Lyons).
Corresponding author and reprints: Shoo K. Lee, MBBS, FRCPC, PhD,
Canadian Neonatal Network, Canadian Neonatal Network Coordinating Centre,
4480 Oak St, Room E-414, Vancouver, British Columbia, Canada V6H 3V4 (e-mail: shool{at}interchange.ubc.ca).
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