Is a New Protocol for Acute Lymphoblastic Leukemia Research or Standard Therapy?

In the United States, doctors generally develop new cancer chemotherapy for children by testing innovative chemotherapy protocols against existing protocols in prospective randomized trials. In the Netherlands, children with leukemia are treated by protocols that are agreed upon by the Dutch Childhood Oncology Group. Periodically, the Dutch Childhood Oncology Group revises its protocols. Sometimes, these revisions are categorized as research, sometimes as treatment. In this Ethics Rounds, we analyze whether enrollment in a new protocol ought to be considered research and, if so, we discuss the implications of that designation. Our discussion highlights the different ways different countries approach complex issues of research ethics.

This Ethics Rounds analyzes a case that illustrates the intertwinement of research and care in the evolution of pediatric oncology. To analyze the case, it is necessary to understand how pediatric oncology innovation is organized in the Netherlands. There, the treatment of acute lymphoblastic leukemia (ALL) in children is developed in a way that is somewhat different from that in the United States. The Dutch approach raises some interesting questions of research ethics.

In Dutch pediatric oncology, patients with ALL are treated by a nationally agreed-upon protocol. Periodically, pediatric oncologists meet to review their results and results from other countries. Based on this analysis, the protocol may be revised. They then treat all patients with the new protocol and carefully monitor outcomes in comparison with historical controls and with studies done in other countries. In various other European countries pediatric oncologists also adapt their treatments according to recent insights without necessarily considering them as research.1

In the United States, most children with cancer are treated on research protocols. These protocols evaluate new approaches to treatment. The new approaches become the standard treatment only if the results of the research show that they are better than existing treatments. In the Netherlands, new or innovative treatment approaches are not necessarily regarded as medical research. Often, innovative treatments are provided without a concurrent, randomly assigned comparison group.

This approach raises a number of questions about the ethics of innovation. Should treatment with a new but professionally endorsed protocol be considered research? If so, should it be reviewed by a research ethics committee (REC)? What sort of consent process is appropriate for this innovative treatment protocol?

With that in mind, we asked experts to analyze a case of innovative treatment in childhood ALL. Our experts include a group of Dutch oncologists and ethicists who are familiar with the system and an American oncologist and bioethicist whose research analyzes the informed consent process.