Discussion
This analysis of participation rates in late effect studies after
childhood cancer illustrates potential factors influencing participation
rates. We included 879 survivors of childhood cancer characterized by
universal access to tax-payed health care, low social inequality, access
to population-based cohorts and complete follow-up using highly valid
and complete registers by use of the civil registration number assigned
to all citizens. We applied a systematic search strategy and sought
additional information from the corresponding authors in case of missing
data.
All studies reported SPR or provided information sufficient to calculate
SPR. Three studies did not clarify study dropouts. Less than three
studies had missing data on age distribution. Study populations ranged
from 15-161 participants, and the outcome measures varied with diverse
clinical examinations such as exercise programs, endocrinologic or
audiologic evaluations, radiologic imaging and neurocognitive
examinations. SPR ranged from 27-100%. The two studies with complete
participation were rather small studies each including 15 patients.
Importantly, SPR varied between diagnostic groups being lowest when
inviting survivors of central nervous system tumors (73%; 95% CI
[0.63-0.81]) or hematologic malignancies (67%; 95% CI
[0.52-0.79]). A tendency towards a higher SPR in studies of solid
tumors compared to hematological malignancies may be due to a different
burden of late effects. Although survivors of solid tumors have an
increased risk of late effects [30, 31], a higher risk is reported
in survivors of hematologic malignancies [32, 33] or central nervous
system tumors [34]. Although the extent of cognitive impairments can
be different in the two patient groups, attention deficits and
impairments in executive functioning among survivors of pediatric acute
lymphoblastic leukemia and central nervous system tumors have been
identified [35, 36]. Executive functions are cognitive high-level
skills, controlling, organizing and planning neurocognitive activity
such as behavioral actions and social learning. Thus, pediatric cancer
survivors may be challenged to read an invitation letter and take the
initiative to reply, due to impaired planning and organizing skills;
this could lead to a lower participation rate.
Attendance in late effect clinics has been widely investigated [37,
38]. Nathan et al. [39] found increased rates of attendance
associated with female gender and higher socieoeconomic status. In our
cohorts, information on sex distribution in the invited participants was
not available, and therefore we could not estimate the sex distribution
in invited compared to the sex distribution of participants accepting to
be enrolled in the study. Further, as recruitment methods were
inconsistently reported, we were not able to investigate if contact by
telephone or letter influenced the participation rate. Harlan et al.
[7] described that extensive efforts were necessary to recruite
adolescents and young adults to complete a questionaire. In the future,
we need to consider more personalized recruitment strategies, as study
populations in late effect studies are heterogenous also regarding age.
We divided the examinations in the studies to be of either short (less
than three hours) or long (more than three hours) duration to evaluate
if a long examination was a potential barrier for participation. Studies
on solid tumors had small samples sizes and always a short duration of
clinical examination and either a long or missing follow-up time. This
might result in discrete changes in small sample sizes being possibly of
disproportionate importance. Five studies included hematologic cancers
with a long duration and long median follow-up time of more than ten
years. This implies that marginal analyses considering one factor at a
time may be explained or confounded by other factors. The five studies
of mixed tumors were quite heterogenous considering participants and
duration of clinical examinations resulting in a more imprecise pooled
estimate for this group.
We did not find any statistically significant differences in time since
diagnosis and duration of examination in our study. The majority of
participants were invited more than ten years after being diagnosed, and
we found that neither time since diagnosis nor the duration of the
examination were challenging in recruitment.
Underreporting of recruitment strategies also made it difficult for
Hudson et al.[40] to evaluate the impact of different recruitment
strategies. They encouraged transparency in the reporting of participant
identification, invitation and consent to enable researchers to
understand research implications, risk of bias and to whom results
apply [40]. This is additional information compared with the current
structured guidelines for observational studies [41].
Although it has been clear for more than four decades that lifelong
survivorship care is needed for most survivors, there is a great
variability in the provision of long-term follow-up programmes for
childhood cancer survivors across countries and thus still an urgent
need for improvement in long-term follow-up care of survivors [42,
43]. Even in the Nordic countries, where late effect clinics are more
widely distributed than in many other countries, a low participation
rate might lead to little or no follow-up of childhood cancer survivors
and thus the risk of an increased morbidity in childhood cancer
survivors.
We encourage future clinical late effect studies to describe the
recruitment procedure more thoroughly including sex distribution of the
invited patients, how patients were contacted and by whom. We believe
that this will lead to a better understanding of the factors influencing
participation rates and thus improved participation.