The German Institute for Quality and Efficiency in Health Care (IQWiG) has found recent clinical data on the use of stem cell transplantation to treat multiple myeloma—a rare and deadly form of cancer—to be inconclusive.
Background and 2012 Conclusion
Stem cell transplantation is a therapy used to treat certain cancers, immunodeficiencies and hematologic diseases. It has also been widely used to treat multiple myeloma. Patients undergoing stem cell transplantation are given high-dose chemotherapy before previously harvested stem cells are transfused into their system.
In 2012, at the request of the Federal Joint Committee (G-BA), IQWiG conducted a benefit assessment of stem cell transplantation therapy for multiple myeloma. The goal of the assessment was to determine the added benefit of therapies involving stem cell transplantation and to draw comparisons to drug treatments such as chemotherapy or immunomodulatory therapy. After reviewing the treatments, IQWiG determined that nine comparisons between therapies were possible.
The assessment took into consideration 16 previous studies involving patients with multiple myeloma to determine several patient-relevant outcomes, including survival time, disease-related adverse events, infections and health-related quality of life.
Of the nine possible comparisons IQWiG sought to make, data from the studies only allowed for five comparisons to be drawn. IQWiG also found that none of the studies looked at health-related quality of life.
One of the major issues IQWiG encountered in its review is the fact that many of the studies it examined were never fully published, making it difficult to draw conclusions from their results. The reviewers also found high risk for bias in many of the studies, and noted that the outcomes of the various studies were mixed, with some pointing to statistically insignificant advantages for stem cell transplantation and others finding no advantage.
As a result, IQWiG found the use of stem cell transplantation should only be used "in the context of clinical studies," and urged researchers to examine quality of life in future studies.
Several years later, in light of recently published literature on stem cell transplantation for multiple myeloma, G-BA has commissioned IQWiG to revisit its previous assessment.
Unfortunately, IQWiG found the new studies did not demonstrate relevant differences between patient groups for any additional comparisons. One study, which compared therapy using donor stem cells and a reduced chemotherapy regime with therapy using the patients' own stem cells and myeloblative conditioning, did not present strong certainty in its results, leading IQWiG to determine that no advantage could be determined.
As a result, IQWiG says it will not stray from its earlier conclusions, citing "unresolved questions," and "gaps in knowledge" in the medical literature. As such, IQWiG still considers stem cell transplantation to be appropriate only in the context of clinical studies, and stresses that patients should be fully informed of the benefits and risks associated with the therapy.
Clinical Data Transparency
In conducting its follow-up assessment, IQWiG took issue with the fact that several large studies were not fully published, despite being complete for years.
"The fact that results of studies that are partly under German management and have been financed mostly by public funds are kept from the public is still unacceptable and contrary to all efforts for more transparency,” said Stefan Lange, deputy director at IQWiG. Lange goes on to note that there have been improvements in the publication of studies primarily funded by industry.
The issue of clinical trials data transparency has been discussed by regulators around the world, with the European Medicines Agency (EMA) and World Health Organization (WHO) taking strides to ensure that the results of clinical trials are published in a timely manner.