R J Stephens1, R E Langley2, P Mulvenna3, M Nankivell2, A Vail4, M K B Parmar2. 1. MRC Clinical Trials Unit, Aviation House, 125 Kingsway, London WC2B 6NH, United Kingdom. Electronic address: richardjamesstephens@gmail.com. 2. MRC Clinical Trials Unit, Aviation House, 125 Kingsway, London WC2B 6NH, United Kingdom. 3. Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne NE7 7DN, United Kingdom. 4. Centre for Biostatistics, University of Manchester, Clinical Sciences Building, Salford Royal NHS Foundation Trust, Stott Lane, Salford M6 8HD, United Kingdom.
Abstract
OBJECTIVES: Guidelines for the conduct of clinical trials emphasize the importance of keeping the interim results from the main endpoints confidential, in order to maintain the integrity of the trial and to safeguard patients' interests. However, is this essential in every situation? MATERIALS AND METHODS: We review the evidence for these guidelines and consider recent randomised trials that have released interim results, to assess their impact on the success of the trial. However, because the strength of opinion to keep interim results confidential is so strong, there are limited examples of such trials. RESULTS: In the QUARTZ trial (which is assessing the value of whole brain radiotherapy in patients with brain metastases from non-small cell lung cancer) the decision to release interim results was taken in response to threatened closure due to poor accrual, whereas in the GRIT trial (which compared two obstetric strategies for the delivery of growth retarded pre-term fetuses) the regular release of interim results was pre-planned. Nevertheless there are a number of common factors between these two trials. In particular, the trial treatments were already in wide use, with no reliable randomised evidence on which treatment should be used for which patients, and there was diverse clinical opinion, which meant that accrual was likely to be challenging. In a situation where a quarter to a third of trials do not accrue their required number of patients, the QUARTZ trial continues to accrue patients, and the GRIT trial successfully accrued its target of nearly 600 babies. CONCLUSIONS: This article therefore argues that there is a need to re-consider whether it is always essential to keep the interim results of randomized clinical trials confidential, and suggests some criteria that may help groups planning or running challenging trials decide whether releasing interim results would be a useful strategy.
OBJECTIVES: Guidelines for the conduct of clinical trials emphasize the importance of keeping the interim results from the main endpoints confidential, in order to maintain the integrity of the trial and to safeguard patients' interests. However, is this essential in every situation? MATERIALS AND METHODS: We review the evidence for these guidelines and consider recent randomised trials that have released interim results, to assess their impact on the success of the trial. However, because the strength of opinion to keep interim results confidential is so strong, there are limited examples of such trials. RESULTS: In the QUARTZ trial (which is assessing the value of whole brain radiotherapy in patients with brain metastases from non-small cell lung cancer) the decision to release interim results was taken in response to threatened closure due to poor accrual, whereas in the GRIT trial (which compared two obstetric strategies for the delivery of growth retarded pre-term fetuses) the regular release of interim results was pre-planned. Nevertheless there are a number of common factors between these two trials. In particular, the trial treatments were already in wide use, with no reliable randomised evidence on which treatment should be used for which patients, and there was diverse clinical opinion, which meant that accrual was likely to be challenging. In a situation where a quarter to a third of trials do not accrue their required number of patients, the QUARTZ trial continues to accrue patients, and the GRIT trial successfully accrued its target of nearly 600 babies. CONCLUSIONS: This article therefore argues that there is a need to re-consider whether it is always essential to keep the interim results of randomized clinical trials confidential, and suggests some criteria that may help groups planning or running challenging trials decide whether releasing interim results would be a useful strategy.
Authors: Avinash Gupta; Corran Roberts; Finn Tysoe; Matthew Goff; Jenny Nobes; James Lester; Ernie Marshall; Carie Corner; Virginia Wolstenholme; Charles Kelly; Adelyn Wise; Linda Collins; Sharon Love; Martha Woodward; Amanda Salisbury; Mark R Middleton Journal: Br J Cancer Date: 2016-10-06 Impact factor: 7.640