†,‡Secondary reports of the same trial were excluded from the calculations. NHMRC, National Health and Medical Research Council; RCT, randomised controlled trial.
Letter to the Editor
Strategies to accelerate recruitment to NHMRC multi-centre clinical trials
Article first published online: 16 JAN 2013
© 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
Journal of Paediatrics and Child Health
Volume 49, Issue 1, pages E103–E105, January 2013
How to Cite
Tarnow-Mordi, W., Simes, J. and Cruz, M. (2013), Strategies to accelerate recruitment to NHMRC multi-centre clinical trials. Journal of Paediatrics and Child Health, 49: E103–E105. doi: 10.1111/jpc.12061
- Issue published online: 16 JAN 2013
- Article first published online: 16 JAN 2013
We estimated the average recruitment period in reports of multicentre randomised controlled trials (RCTs) funded by the National Health and Medical Research Council (NHMRC) in the New England Journal of Medicine between January 2001 and December 2011. The terms ‘trial’ and ‘Australia’ were entered into the New England Journal of Medicine Advance Search facility on its website (http://www.nejm.com), yielding 177 articles, from which 20 RCTs that were fully or co-funded by NHMRC were identified. The mean recruitment period for all 20 RCTs was 4 years 11 months (range 1 year 9 months to 9 years 10 months). However, the mean recruitment period was 18 months longer for the 11 RCTs with primary neonatal or paediatric outcomes than for the other nine adult trials (Table 1). These recruitment periods do not include the time needed for follow-up.
|Date||Authors/title||Patient group||Primary outcome||No. of patients||No. of sites||Recruitment period|
|2011||INIS Collaborative Group (NHMRC 301973). Treatment of neonatal sepsis with intravenous immunoglobulin. NEJM 365: 1201–11.||Newborn infants||Death or disability||3 493||113||6 years|
|2011||Stenson et al. Increased 36 week survival with high oxygen target in very preterm infants. NEJM 364: 1680–82.||Preterm infants||Death||2 316||36||5 years|
|2011||Cooper, et al. Decompressive craniectomy in diffuse brain injury. NEJM 364: 1493–502.||Adults||Death or disability||155||15||9 years 5 months|
|2010||Zoungas et al. Severe hypoglycemia and risks of vascular events and death. NEJM 363:1410–18.||Adults||Death or vascular events||11 140||215||1 year 9 months|
|2010||Cooper et al. A randomized, controlled trial of early vs. late initiation of dialysis. NEJM 363: 609–19.||Adults||Death||828||32||8 years 4 months|
|2009||Craig et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. NEJM 361: 1748–59.||Children||Urinary infection||576||–||8 years 4 months|
|2009||RENAL Replacement Therapy Study Investigators. Intensity of continuous renal replacement therapy in critically ill patients. NEJM 361: 1627–38.||Adults||Death||1 508||35||2 years 9 months|
|2009||NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. NEJM 360: 1283–97.||Adults||Death||6 104||43||4 years|
|2009||Buchbinder et al. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. NEJM 361: 557–68.||Adults||Pain||78||–||4 years 7 months|
|2008||Karunajeewa et al. A trial of combination antimalarial therapies in children from papua new guinea. NEJM 359: 2545–57.||Children||Treatment response||677||2||2 years 3 months|
|2008||Rowan et al. Metformin vs. insulin for the treatment of gestational diabetes. NEJM 358: 2003–15.||Women||Neonatal morbidity||751||10||4 years 2 months|
|2008||Morley et al. Nasal CPAP or intubation at birth for very preterm infants. NEJM 358: 700–8.||Preterm infants||Death or BPD||610||17||6 years 10 months|
|2007||Schmidt et al. Long term effects of Caffeine Therapy for Apnea of Prematurity. NEJM 357: 1893–1902.†||Preterm infants||Death or Disability||2 006||36||5 years|
|2007||Crowther et al. Outcomes at 2 years of age after repeat doses of antenatal corticosteroids. NEJM 357: 1179–89.||Infants||Disability free survival||1 047||23||6 years 2 months|
|2007||SAFE Study Investigators. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. NEJM 357: 874–84.‡||Adults||Death|
|2006||Schmidt et al. Caffeine therapy for apnea of prematurity. NEJM 354: 2112–21.†||Preterm infants||BPD|
|2006||Elkins et al. A Controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. NEJM 354: 229–40.||Adults||Lung function||164||15||2 years 4 months|
|2006||Rumbold et al. Vitamins C and E and the risks of pre-eclampsia and perinatal complications. NEJM 354: 1796–806.||Women||Pre-eclampsia, death or morbidity, SGA||1 877||7||3 years 1 month|
|2005||Crowther et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. NEJM 352: 2477–86.||Women||Infants: death, morbidity or prematurity||1 000||18||9 years 10 months|
|2004||SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. NEJM 350: 2247–56.‡||Adults||Death||6 997||15||1 years 8 months|
|2003||Askie et al. Oxygen-saturation targets and outcomes in extremely preterm infants. NEJM 349: 959–67.||Preterm infants||Growth and development||358||8||4 years|
|2003||Wing et al. A comparison of outcomes with angiotensin-converting–enzyme inhibitors and diuretics for hypertension in the elderly. NEJM 348: 583–92.||Adults||Cardiovascular events||6 083||–||3 years 3 months|
|Average recruitment period in RCTs in infants or children (n = 11)||5 years 6 months|
|Average recruitment period in RCTs in adults (n = 9)||4 years 0 month|
|Average recruitment period in all RCTs (n = 20)||4 years 11 months|
All these trials are likely to have significant impact on clinical practice, because they were reported in the world's most highly cited medical journal. They illustrate the need to invest considerable resources and time, often well beyond 5 years, to address important study questions, rather than curtailing recruitment, diminishing power and scientific validity.
What strategies might accelerate recruitment? Several trials in the table employed international collaboration to achieve samples of hundreds or thousands. Another strategy to accelerate recruitment, not yet widely employed in Australian trials nor exemplified in the Table, is to establish fully funded networks of local research coordinators, in sites with adequate volumes of patients.
Government-funded clinical networks, which include local site research nurses or coordinators to support clinical trials, have already been established to improve the co-ordination, speed and quality of randomised controlled cancer trials in Australia[2, 3] and of paediatric and neonatal trials in the United Kingdom. Similar investment merits consideration in other specialties in Australia, particularly in perinatal, neonatal and paediatric clinical trials, where life expectancy in survivors spans several decades.
A third strategy is to engage consumers and parents as full partners in all aspects of the design, conduct and implementation of trials. This may enhance their relevance to patients and accelerate recruitment and the implementation of their results.
- 1Cancer Australia. Support for clinical trials. Available from: http://%20www.canceraustralia.gov.au/research-and-funding/support-clinical-trials [accessed 20 January 2012].
- 3Medicines for Children Research Network (MCRN). Available from: http://www.ctuprod.liv.ac.uk/mcrnweb/index.php [accessed 20 January 2012].
- 4Evaluating therapeutic hypothermia: parental perspectives should be explicitly represented in future research. Arch. Pediatr. Adolesc. Med. 2012; 166: 578–579., , .