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Dear Editor,

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.

Table 1. Reports of NHMRC-funded multicentre randomised controlled trials in N Engl J Med, 2001–2011
DateAuthors/titlePatient groupPrimary outcomeNo. of patientsNo. of sitesRecruitment period
  1. †,‡Secondary reports of the same trial were excluded from the calculations. NHMRC, National Health and Medical Research Council; RCT, randomised controlled trial.

2011INIS Collaborative Group (NHMRC 301973). Treatment of neonatal sepsis with intravenous immunoglobulin. NEJM 365: 1201–11.Newborn infantsDeath or disability3 4931136 years
2011Stenson et al. Increased 36 week survival with high oxygen target in very preterm infants. NEJM 364: 1680–82.Preterm infantsDeath2 316365 years
2011Cooper, et al. Decompressive craniectomy in diffuse brain injury. NEJM 364: 1493–502.AdultsDeath or disability155159 years 5 months
2010Zoungas et al. Severe hypoglycemia and risks of vascular events and death. NEJM 363:1410–18.AdultsDeath or vascular events11 1402151 year 9 months
2010Cooper et al. A randomized, controlled trial of early vs. late initiation of dialysis. NEJM 363: 609–19.AdultsDeath828328 years 4 months
2009Craig et al. Antibiotic prophylaxis and recurrent urinary tract infection in children. NEJM 361: 1748–59.ChildrenUrinary infection5768 years 4 months
2009RENAL Replacement Therapy Study Investigators. Intensity of continuous renal replacement therapy in critically ill patients. NEJM 361: 1627–38.AdultsDeath1 508352 years 9 months
2009NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. NEJM 360: 1283–97.AdultsDeath6 104434 years
2009Buchbinder et al. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. NEJM 361: 557–68.AdultsPain784 years 7 months
2008Karunajeewa et al. A trial of combination antimalarial therapies in children from papua new guinea. NEJM 359: 2545–57.ChildrenTreatment response67722 years 3 months
2008Rowan et al. Metformin vs. insulin for the treatment of gestational diabetes. NEJM 358: 2003–15.WomenNeonatal morbidity751104 years 2 months
2008Morley et al. Nasal CPAP or intubation at birth for very preterm infants. NEJM 358: 700–8.Preterm infantsDeath or BPD610176 years 10 months
2007Schmidt et al. Long term effects of Caffeine Therapy for Apnea of Prematurity. NEJM 357: 1893–1902.Preterm infantsDeath or Disability2 006365 years
2007Crowther et al. Outcomes at 2 years of age after repeat doses of antenatal corticosteroids. NEJM 357: 1179–89.InfantsDisability free survival1 047236 years 2 months
2007SAFE Study Investigators. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. NEJM 357: 874–84.AdultsDeath   
2006Schmidt et al. Caffeine therapy for apnea of prematurity. NEJM 354: 2112–21.Preterm infantsBPD   
2006Elkins et al. A Controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. NEJM 354: 229–40.AdultsLung function164152 years 4 months
2006Rumbold et al. Vitamins C and E and the risks of pre-eclampsia and perinatal complications. NEJM 354: 1796–806.WomenPre-eclampsia, death or morbidity, SGA1 87773 years 1 month
2005Crowther et al. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. NEJM 352: 2477–86.WomenInfants: death, morbidity or prematurity1 000189 years 10 months
2004SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. NEJM 350: 2247–56.AdultsDeath6 997151 years 8 months
2003Askie et al. Oxygen-saturation targets and outcomes in extremely preterm infants. NEJM 349: 959–67.Preterm infantsGrowth and development35884 years
2003Wing et al. A comparison of outcomes with angiotensin-converting–enzyme inhibitors and diuretics for hypertension in the elderly. NEJM 348: 583–92.AdultsCardiovascular events6 0833 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.[1]

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.[4] 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.[4]

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