1029 Placebo vs comparator drugs in paediatric drug trials

Significant ethical considerations come into play when drug trialists engage in randomized controlled studies, particularly when the trials involve children. Overall in drug trials there has been a move from new drug vs. placebo to new drug vs. existing standard-of-care drug. This for a number of reasons, the most important of which is that if one is testing the drug on known patients who are responsive to a medication one does not want to withdraw the effective product and expose the subject to the potential consequences of the underlying medical condition. In favour of new drug vs. standard-of-care product is the need to know the incremental benefits of new drug in terms of cost benefit, cost effectiveness, cost utility and other health economic measures. However, when dealing with children there are additional considerations. For starters it is acknowledged that scientifically speaking, placebo-controlled randomized studies generate the most reliable data and with smaller sample sizes than if one is using comparator drugs (unless of course there is a massive difference in efficacy between the products being tested). Using a placebo also obviates the possibility of a minimally-effective or ineffective drug being tested against an equally ineffective chemical variant (which would result in a conclusion that there is no benefit in adopting the new product rather than rejecting both as ineffective). Ethicists also comment on the fact that in many cases, standard-of-care in paediatric practice is essentially ‘off-label’ because utilization is derived or inferred from adult studies, and actual studies have not been done in children. This also favours placebo control since the standard-of-care in such a case could not be used as a comparator. As stated above, placebo-controlled studies are likely to require smaller numbers, and here two issues come into play: 1) the trial would expose smaller numbers to risk (in both groups), and 2) by nature, the paediatric population is quite small and recruitment of minor subjects is often difficult. In reality it is often difficult to recruit subjects (adults or minors) into placebo-controlled studies because potential randomization into a placebo arm causes anxiety, as would the risk of washing out an effective drug during the pre-trial washout phase. Final decisions as to which way to go depend on careful consideration, taking clinical, ethical and legal issues into account.

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Eur J Pediatr 2010 DOI 10.1007/s00431-010-1268-6
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