Only 2 percent of pediatric trials reported using independent safety monitoring committees that can help lead to the early detection of adverse drug reactions, according to a major review published in the journalActa Paediatrica. Child health researchers from The University of Nottingham carried out a detailed analysis of 739 international trials published between 1996 and 2002, to determine safety measures were in place to monitor levels of adverse drug reactions. While 74 per cent of the trials described how safety monitoring was performed during the study, only 2 percent, or 13 studies out of 739, had independent safety monitoring committees. Here is the study. And here are some tables.
"We were very surprised by the low level of trials that had independent safety monitoring committees and are urging pharmaceutical companies to include these in all future trials involving children," says Helen Sammons, the lead author and an associate professor of child health in the University's Academic Division of Child Health, in a statement. “It is essential that drugs are developed for use in children and clinical trials need to continue. They are vital because they increase the chance of picking up adverse reactions before drugs are introduced into general clinical practice.”
The findings included...
- Seven of 10 trials reported adverse events and a fifth reported a serious adverse event, ie. an untoward medical occurrence, not necessarily related to a drug; - Adverse reactions were reported in just under 37 percent of trials, with 11 percent reporting moderate or severe adverse reactions; - Six clinical trials, which had safety monitoring committees, were terminated early because of significant drug toxicity; - Deaths were reported in 11 percent of the trials, but the majority were thought to be unrelated to the drug use; - Death rates were highest in trials involving newborn babies, with 56 percent of the 99 trials included reporting a death; - Other major specialities in which deaths were reported included infectious diseases, neurology, respiratory and kidney problems. Only papers published in English on the Medline database during the seven-year study period were included and the authors excluded studies that covered HIV and cancer because of high deaths rates from the actual diseases. Just over half of the studies compared a drug with a placebo another 35 percent involved a new med. A smaller percentage, 26 percent, involved a direct comparison between two established drugs. Some of the trials included adults as well as children.
Studies reporting severe drug toxicity problems came from a wide range of countries, including Argentina, Belgium, Canada, Chile, China, France, India, Israel, Italy, Japan, Netherlands, South Africa, Sweden, Taiwan, Thailand, Turkey, UK and the USA. Adverse drug reactions included bleeding, high blood pressure, seizures, psychosis, suicide, acute renal failure and death.
The researchers stress that clinical drug trials in children are essential for the development of medicines and to provide evidence of the best treatments for specific conditions. But they feel that greater safety measures and awareness of the risk is essential.
“We need to test drugs on children as the only other options are to use unlicensed drugs or prescribe drugs that have been licensed for adults off-label - outside the terms of their licence,” says Sammons. "But we feel that the small number of studies that reported having safety monitoring committees was unacceptable. It is invaluable to have an independent monitor who can swiftly question any adverse drug reactions or differences in illness and death rates between groups taking part in the clinical trials.
“Parents also need to be made aware of the risks of adverse drug reactions when a child takes any medicine so that they can make informed decisions that balance those risks against the possible benefits the drug may provide their child. In a drug trial this should include information on the mechanisms that will be used during the clinical trial to safeguard the children taking part.”
Sammons points out that the number of pediatric trials is likely to rise in the European Union, following new legislation that provides drugmakers with a valuable financial incentive – a six-month extension to their exclusive manufacturing license for a drug if children are included in the clinical trials. Similar legislation has been in place in the US for over five years and has led to an increase in drug trials that include children.
“There is general agreement by paediatric health professionals, regulatory authorities and the pharmaceutical industry, as well as politicians and parents, that drug trials are essential in order to improve drug therapies," she says. "We are calling for all paediatric drug trials to include independent safety monitoring committees to ensure that this vital work is carried out in a way that minimises risks, and maximises benefits, for the children taking part.”
UPDATE: Sammons writes us to say: "We did not analyze the funding body in my analysis of the trials. It was not available in many papers...We did not look at the data for the drugs within the adult population so are unable to comment on trials in the adult population or there comparison with children. There is no evidence looking at safety monitoring committees and providing comparison for their impact on safety related events. Our piece of work was an overview of the situation in paediatrics in terms of adverse events taking place and ADR's. We observed that the trials that were stopped due to severe ADR's had a high proportion of safety monitoring committees that made this decision."