Discussion
In this paper, we described the methodology, participation rates, and data availability of the DCCSS LATER 2 study. With the clinical data collected in the LATER 2 study, we will be able to fill gaps in knowledge that have been identified in the published recommendations of the International Guideline Harmonization Group (IGHG).7
The LATER 2 study collected extensive data on clinical outcomes and questionnaires for 2,519 childhood cancer survivors, 632 siblings and 580 parents. The data collection was finished in 2020. An important strength of our study is that we evaluated objective clinical outcomes by diagnostic tests using blood and urine samples in combination with functional tests, and therefore do not rely solely on self-reported outcomes, which can be prone to recall bias. Another strength is that we used validated questionnaires for our outcomes. Furthermore, by including siblings for some outcomes, we will be able to compare prevalence of outcomes and with a control group. The availability of detailed information on childhood cancer diagnosis and treatment enables in-depth analyses on potential risk factors for clinical outcomes.
In the LATER 2 study there is a risk of participation bias, as we found some differences between participants and non-participants in sex, type of cancer, and as a result also in childhood cancer treatment. This might under- or overestimate the prevalence of health outcomes. The consequences of these differences may vary between outcome-specific sub-studies. Therefore, differences between the participants and non-participants will be tested for each sub-study to evaluate specific patterns of potential (participation) bias specific to the health outcomes evaluated per sub-study.
The collected clinical data will be a repository for future studies. After completion of the primary studies on the a priori-defined clinically relevant research questions, we will combine data from different sub-studies, e.g. metabolic syndrome and cardiac diseases and quality of life related to medical outcomes, to answer further questions, which may also include health outcomes ascertained using record linkage in the LATER 1 study (e.g. benign and malignant tumors). In the future, it will be also be possible to link clinical parameters measured during the LATER 2 study to health outcomes that occur later.
The current study is one of the largest clinical study among childhood cancer study and includes a large variety of clinical outcome data collected in all types of childhood cancer survivors. As far as we are aware, the St. Jude Lifetime Cohort study represents the only other endeavor of this scale covering the full spectrum of childhood cancer types in which the burden of clinical outcomes is ascertained during a clinical visit.8 Future collaboration will be important to improve knowledge on rare health outcomes.
In summary, in the LATER 2 study extensive information on various clinical and (psychosocial) health outcomes has been assessed during an outpatient clinic visit in a large group of childhood cancer survivors. The high-quality data will provide valuable insights into risks of and risk factors for clinical and (psychosocial) health outcomes and factors for early recognition of (psychosocial) health outcomes in long-term childhood cancer survivors. With this information, we will contribute to important gaps in knowledge and finally improve the quality of life and care for childhood cancer survivors.