Introduction In order to assess the requirements of the European Medical Agency (EMA) for paediatric clinical trials in nephrology we assessed the decisions on Paediatric Investigation Plans (PIPs), which are required to get approval for new drugs. Paediatric nephrology comprises rare indications, but also frequent paediatric conditions. Clinical trials are needed in order to base therapy on ev-idence, but the relevant population can be very small in paediatric nephrology.
Methods All 20 decisions on PIPs published by the EMA on the EMA website under ‘uro-nephrology’ were includ-ed. Data are presented as proportions (categorical data) and median (range) (numerical data).
Results Full and partial waivers: 7 of the published decisions granted a full waiver (i.e., no paediatric studies required). For the remaining 13, a PIP was agreed. For 6 of those 13 PIPs, a partial waiver was granted for certain ages (0–6 months (2x), 0–5, 0–6, 0–8, 12–18 years.Agreed PIPs: The PIPs require the conduct of 0–3 (median 1) quality studies, 0–2 (median 0) non-clinical studies, and 1–6 (median 3) clinical studies. As there are ca. 9 paediatric dialysis subjects per million of all paediatric subjects, an estimate of the number of paediatric dialysis patients in EU is roughly ca. 400 patients. At least 4 PIPs require in-clusion of paediatric dialysis subjects, requiring 14 clinical studies, i.e., ca. 14 subjects are available for each of those studies. There are no concessions in powering the studies, and therefore, the required numbers will be much higher than the available number of subjects in EU.
Time for decision and time for completion of PIP: The time between start of the procedure and the decision of the PdCo/EMA was 103 days (35–468 days). The time between the date of decision of the PdCO/EMA and the date of the required completion of the PIP ranged from 0.03 years – 13.47 years (median 4.84 years).
Conclusion All partial waivers affected the lowest age groups. Although the youngest age groups need an eval-uation of new substances most urgently, the number of granted partial waivers indicates how difficult it is to con-duct clinical trials in this subpopulation. However, only 4 of the 13 agreed PIPs are concerned with frequent indi-cations, while 9 of those aim at rare indications. For those 9, a median of 3 clinical studies is required. It is unlikely that the required number of subjects can realistically be recruited. Further, the required studies make the timely conduct (median time 4.84 years) and completion at the same time as the studies in adults questionable. This could delay approval in adults. In summary, we show some im-balances: a) studies are most difficult in infants, but they need them most, b) the number of subjects required does not fit the indication epidemiology, c) timelinies for com-pleting paediatric studies are difficult to meet.
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