The pediatric rheumatic diseases (PRD) are rare conditions associated with substantial morbidity, consequence on the quality of life, and monetary costs. Many studies of the impact and outcome of PRD have shown that this group of diseases is associated with greater morbidity and monetary cost than previously thought. For example, long term outcome studies of children with juvenile idiopathic arthritis (JIA) report that, after a mean follow-up of 15 years, the majority of the patients continue to experience some difficulties in daily living activities, and that moderate to severe pain is still present in 30% of the patients. There is also evidence of cumulative organ damage in patients with juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM).
Certainly childhood chronic illnesses with high levels of morbidity should be the target of intense research aimed at ameliorating and/or curing the disease. However, conducting clinical trials in PRD has proven difficult for a host of reasons.
Due to the rarity of the diseases the only possibility to gather a sufficient number of patients to obtain clinically and statistically valid results in a reasonable period of time, is to perform multi-centre studies on an international scale. The ethics of conducting any placebo-controlled trial, even in adults, has recently come under intense debate. Parents often refuse entry into studies because they are uncomfortable with the prospect of their child being assigned by chance to placebo. Securing funding for conducting clinical trials in PRD has always been difficult since the pharmaceutical industry has little interest in funding these trials due to the small potential market.
Drugs available for the treatment of PRD have been used in new dosages, new routes of administration, and new combinations. Unfortunately, data regarding the safety and effectiveness of these new treatment regimens tends to be from small, open, anecdotal, uncontrolled, non-randomized case series. Examples include the use of high dose MTX in recalcitrant JIA and of MTX usage in juvenile dermatomyositis. Many of these new approaches to management may represent improvements over existing standards, but without larger, systematic trials the data must remain suspect.
PRINTO foundation and goals
PRINTO is a non governmental international network founded by Alberto Martini and Nicolino Ruperto in 1996, and initially included 14 European countries, with the goal to foster, facilitate and co-ordinate the development, conduct, analysis, and reporting of multi-centres, international clinical trials and/or outcome standardisation studies in children with paediatric rheumatic diseases (PRD).
PRINTO was founded with the idea to perform clinical trials for the PRD with or without the support of pharmaceutical companies. In general, if a study is not supported by a pharmaceutical company the design is that of a randomized, actively controlled, and open label clinical trial. If the study is supported by a pharmaceutical company and is part of a clinical development program which aims for marketing an agent, more classic design are used.
PRINTO is composed of academic, clinical centres actively engaged in the research/clinical care of children with PRD. PRINTO actually groups the most esteemed paediatric rheumatology researchers worldwide.
PRINTO has four main vertical structures:
the Advisory Council that provide leadership and guidance for PRINTO research activities;
the International Coordinating Centre whose main task it to facilitate the flow of logistic and scientific details needed to design, launch and manage multi-centered, multi-national, collaborative studies;
the National Coordinating Centres (one per country) whose tasks are to facilitate the participation of the greatest number possible of individual centers, and to provide the translation of all the forms to be completed by the parents/patients; and finally
the Individual Clinical Centres that constitute the main support structure to obtain a critical mass of data for on-going and future research.