Cancer Experts Call for Major Research Changes

Increasingly strict regulatory controls governing clinical research pose a severe threat to the development of new cancer medicines for children, and may jeopardize recent improvements in survival, according to a special edition of Lancet Oncology.

The publication was designed to coincide with a meeting in Brussels, Belgium, on February 20, 2013 about how to enhance and optimize pediatric clinical research through the EU Clinical Trials Regulation. The event was hosted by Glenis Willmott, Member of the European Parliament (MEP) and EP Rapporteur of the European Union Clinical Trials Regulation proposal, and was organized in collaboration with the European Society for Pediatric Oncology (SIOP Europe).

"In high-income countries, we have nearly reached optimization of present anticancer treatments," said Kathy Pritchard-Jones, Professor from the Institute of Child Health, University College London, UK. "New regulatory approval and research strategies are urgently needed to speed the development of new, effective, and safer treatments for children with cancer if we are to continue to improve the cure rate, reduce toxicity compared to existing treatments, and minimize side effects in later life."

In recent years, clinical trials in children have been carried out largely to meet regulatory requirements, and have been driven by the pharmaceutical industry rather than pediatric oncology experts who understand the unmet clinical needs of children and young people with cancer, according to the Lancet Oncology authors. The trend for industry to drive the development of clinical research plans contrasts with the need for broad research and development partnerships that can deal with complex biology and drug development, they noted.

"Fostering open collaborations with many groups from industry, regulatory bodies, academia, governments, and patient advocacy will be crucial to speeding up drug development," said co-author Gilles Vassal, a Professor at Institut Gustave Roussy, Paris-Sud University, France. "The key is precompetitive collaboration that benefits all stakeholders, ensuring broad access to the results."

Although more children and young people in high-income countries are surviving cancer than ever before, cancer remains the leading cause of death from disease in children aged one to 15, and more than 5,000 children still lose their lives to cancer every year in these regions. Increased participation in international, collaborative clinical trials has helped to raise survival from 30% to 80% over the last 50 years.

"But an increasingly complex and strict regulatory environment for clinical research and data sharing is limiting children's access to early-phase clinical trials and delaying the development of new drugs," explained Richard Sullivan, Professor of Cancer Policy and Global Health at King's College London. "For example, the implementation of the EU Clinical Trials Directive, in 2004, has almost quadrupled costs, led to substantial delays, and even the discontinuation of trials."

Other factors leading to longer clinical development include the complex nature of the biology underlying childhood cancers, the difficulty of identifying targets suitable for drug treatment, a lack of long-term sustainable funding for research and development, particularly outside the United States, and little economic incentive for pharmaceutical companies to develop anticancer drugs adapted for children, the authors noted.

To fast-track the most relevant and new medicines for childhood cancers will require a renewed focus on the potential role of adult cancer drugs in children, as well as methods and clinical trial design that aim to more rapidly predict the optimal (i.e., effective and safe) dose.

"New biology-driven approaches are needed, but this will only be achieved through increased international cooperation in clinical trials and sharing of research tissue samples and data," commented Pritchard-Jones. "This is necessary as these diseases are already rare, and dividing patients into increasingly smaller biological subgroups might amount to just a handful of trial participants a year in each country."

The introduction of less toxic and more targeted drugs necessitates a partnership between clinical and translational researchers, the pharmaceutical industry, drug regulators, and patients and their families, she said. More needs to be done to address the long-term consequences of cancer treatment. Estimates suggest that one in 1,000 adults in high-income countries are survivors of childhood cancer, and 40% of these survivors experience adverse effects throughout life.

"These are serious issues that can have a real impact on a person's quality of life," stated Sullivan, "It is essential that academic programs and trial investigators ensure better follow-up of survivors to appropriately address the complications childhood cancer survivors may experience in later life."

"If policy makers continue to fail to pay attention to this issue then in 10 years...the infrastructure will not be in place to deal with what will have become the most common disease-related cause of death in childhood," the authors stated.

—Philip Ward