At present, several innovative compounds are being tested in clinical trials in order to improve the treatment of Acute Lymphoblastic Leukemia (ALL). However, these trials measure different outcomes, thus questioning their comparability. In addition, the majority of clinical trials do not assess long-term side effects and their influence on the patients’ quality of life. A core outcome set (COS) may assist researchers in selecting outcomes for future trials, thereby promoting harmonization of ALL studies and improving clinical management of the disease.
Acute Lymphoblastic Leukemia (ALL) is a life-threatening disease if not treated immediately. The treatment of ALL has dramatically improved in the past few decades, largely due to improvements in protocol design, supportive care, and risk stratification. The five-year event-free survival currently is more than 80% for children and 30-70% adults largely depending on age. ALL treatment protocols are intensive, typically involving multiple chemotherapeutic drugs administered over several months or years. The drugs are toxic and may cause substantial long-term morbidity, particularly in pediatric patients. To improve the treatment of ALL, several novel compounds are currently being tested in clinical trials. Unfortunately, these trials are insufficiently comparable because they measure different outcomes. In addition, the majority of trials do not assess long-term side effects and their influence on patients’ quality of life. Defining a core outcome set may offer a solution to these problems.
A COS is a minimum set of outcomes to be collected in future clinical trials which, ideally, have been agreed upon by all stakeholders. The COS is intended as an international standard to evaluate ALL treatments in clinical trials and other research settings (e.g., registry and observational studies). Using a COS will improve the comparability of clinical trials, enhance the consistency of reporting, and reduce selective reporting bias. The COS can also be incorporated into clinical guidelines and be used to improve patient management. This project aims to identify a COS for ALL that will be accepted by all of HARMONY’s stakeholder groups.
The researchers will use the Delphi method to develop the COS. First, a preliminary list of about 60 outcomes was created, which is based on literature research and expert interviews. Next, a panel of stakeholders will be asked to rate the importance of each outcome on the basis of their personal experiences. Three iterative rounds are planned, using an online survey tool (COMET). After each round, the participants will receive an anonymized summary of the survey results per stakeholder group. This will allow them to revise their answers in the next round. It is expected that the group will converge towards a consensus COS after a number of iterations. The process will be stopped after pre-defined consensus criteria have been achieved. The final version of the COS will be aligned in a meeting with all participants.
Panel participants will be recruited from HARMONY Partners, including clinicians, patients, representatives from the pharmaceutical industry, and health authorities. The aim is to recruit equal participant numbers for all stakeholder groups wherever possible. This project is part of a series of Delphi studies for the seven hematological malignancies that are being studied by the HARMONY Alliance. In the future, a COS applicable to all seven hematological malignancies will be defined.
Download the Delphi ALL Study Protocol document to inspect the full outcome list in Annex 1 >