Explaining Randomisation to Potential Clinical Trial Participants Healthcare consumers helping to explain randomisation using the CORD pilot RCT as the example Gill Gyte, Sally Crowe & Dell Horey 4th International Clinical Trials Methodology Conference Liverpool, May 2017 I hope this presentation will be an illustration of how we can harness the skills of healthcare consumers to develop wording to explain randomisation to people invited to participate in clinical trials. I would like to thank Sally Crowe and Dell Horey for their amazing contribution to this work and their input to running the workshop.

Background Launch of CORD pilot trial - March 2013 Current clinical practice / CORD pilot RCT / oral assent / brief explanation Clinicians had difficulties explaining randomisation briefly to women, particularly in explaining why women could not choose their group allocation Developed a workshop for healthcare consumers at the Cochrane Colloquium in Quebec City 2013 ‘The wonders of randomisation – a workshop for consumers’ This story begins at the launch of CORD pilot trial - March 2013 This was a feasibility RCT looking at delayed cord clamping with stabilisation and resuscitation (if required) given at the mother’s side versus standard immediate cord clamping in babies born less that 32 weeks gestation. Many women in very preterm birth will give birth very quickly and so to include these women in the trial we sought and received permission from the ethics committee to use an ‘oral assent’ process of recruitment if birth was very imminent. This involved, information available antenatally and if the clinician thought labour was imminent and there was not time for full informed consent, then he/she would explain the trial briefly to the woman and invite her to participate. If she agreed then she was randomised and after the birth full informed consent would be requested. So it was important to be able to explain the trial briefly but with sufficient information to make consent valid. So, Lelia invited actors to play the part of women in very preterm labour being invited to participate in CORD pilot trial and clinicians were invited to act out inviting the woman into the trial. They were brilliant and one woman said she would agree to participate and wanted to be in the delayed clamping group. This caused problems - how to explain that she could not choose. Clinicians had difficulties explaining randomisation briefly and in language women could understand. This was especially true when the woman said she would join the trial and wanted delayed cord clamping. None of us could explain simply why she could not choose which group she would be in. Shared suggestion of a workshop for healthcare consumers at the Cochrane Colloquium in Quebec with Sally Crowe & Dell Horey “The wonders of randomisation – a workshop for consumers’

Workshop objectives For consumers to be able to describe the concept, process and outcomes of randomisation in clinical trials, and how to minimise bias through the methods chosen. For consumers to develop wording to explain randomisation to women invited to participate in the CORD pilot trial, in particular to cover why women cannot choose their group and why random allocation is critical. For consumers to be able to describe the concept, process and outcomes of randomisation in clinical trials, and how to minimise bias through the methods chosen. For consumers to develop wording to explain randomisation to women invited to participate in the CORD pilot trial, in particular to cover why women cannot choose and why random allocation is critical.

Workshop description This was an interactive workshop, using CASP methodology. Workshop members given magazine advert promoting purported clinical benefits and asked to design a study that would address the claims. Discussion progressed to the concept of randomisation, bias and how study design can minimise bias. In the second part of the workshop, participants, in small groups, developed statements describing randomisation to someone invited to participate in CORD pilot trial. These statements were discussed by all workshop participants and modifications suggested. This was an interactive workshop, using CASP methodology. An advert from a magazine (that claim benefits or clinical effects) is used and working in small groups, we ask participants to design a study that would address the claim made in the advert. Discussion progresses to the concept of randomisation and the biases that can be reduced through careful design in clinical trials. In the final part of the workshop, participants, in 3 small groups, developed statements describing randomisation to someone invited to participate in CORD. These statements were discussed by all workshop participants and modifications suggested.

Workshop participants 5 participants – 4 were consumers – 3 were mothers Workshop time cut to 1 hour, however all participants had been at a previous CASP workshop at a Cochrane Colloquium Discussed in detail the aspects of randomisation which minimise bias Participants only had about 10 minutes to develop their explanations of randomisation. There were three small groups which included the workshop facilitators. Clash with other workshops for consumers 5 participants – 4 were consumers – 3 were mothers. All participants had been at a previous workshop we had run where participants had an advert and had designed an RCT We discussed in detail the aspects of randomisation which minimise bias. Workshop time cut to 1 hour – so participants only had about 15 minutes to develop their explanations of randomisation. There were three small groups, two with 2 or 3 participants and the workshop facilitators created the third group.

What consumers thought Consumers disliked: “We do not know which form of care is better” – this caused anxiety They were happy with: “We are wanting to find out which form of care is better” The words ‘random’, ‘allocated randomly’ or ‘chance’ – it seemed wrong to leave the care they were to receive to chance “Letting the computer choose” Consumers disliked: “We do not know which form of care is better” – this caused anxiety They were happy with: “We are wanting to find out which form of care is better” The words ‘random’, ‘allocated randomly’ or ‘chance’ – it seemed wrong to leave the care they were to receive to chance They were happy with “Letting the computer choose”

Group 1 “Nobody knows the treatment until the event happens - not the patients or healthcare providers. The computer makes the choice, then it is a fair test between the two timings of cord clamping. Once you give consent the progress of your early birth will not influence your treatment. Either way we will care for you and your baby. ” “Nobody knows the treatment until the event happens - not the patients or healthcare providers. The computer makes the choice, then it is a fair test between the two timings of cord clamping. Once you give consent the progress of your early birth will not influence your treatment. Either way we will care for you and your baby. ”

Group 2 “The women in labour (who are coming in before 32 weeks) and are in this study must ‘take turns’  – the computer decides which Mom does it this way, and which Mom does it the other way. That way we will have similar groups of Moms doing each treatment – and the study results will be reliable.  Either way we will do our best to care for you and your baby.” “The women in labour (who are coming in before 32 weeks) and are in this study must ‘take turns’  – the computer decides which Mom does it this way, and which Mom does it the other way. That way we will have similar groups of Moms doing each treatment – and the study results will be reliable.  Either way we will do our best to care for you and your baby.”

Group 3 “We want to find out which way to clamp the cord is better for babies and mothers, so we are trying out different timings with similar groups of Mums and comparing the results. We want a good mix of Mums in both groups. We know that if we let people choose (either you or us) we don’t do it well. If the computer chooses, it works better and we end up with results we can trust. Either way we will do our best to care for you and your baby.” “We want to find out which way to clamp the cord is better for babies and mothers, so we are trying out different timings with similar groups of Mums and comparing the results. We want a good mix of Mums in both groups. We know that if we let people choose (either you or us) we don’t do it well. If the computer chooses, it works better and we end up with results we can trust. Either way we will do our best to care for you and your baby.”

Back to CORD meeting We don’t do it well – make statements positive Start off with best care Don’t use ‘patient’ or ‘end up’ “Either way we will care for you and your baby.” Ethics committees requirement for ‘Participants Information Leaflet (PIL)’. “Either way we will care for you and your baby.” We don’t do it well – make this positive Start off with best care Don’t use ‘patient’ or ‘end up’ There was general dislike of the ethics committee requirement for so much information in a ‘Participants Information Leaflet (PIL)’. Further research is needed to see if these requirements help or hinder recruitment to clinical trials.

Conclusions With a carefully thought through interactive workshop, healthcare consumers can contribute to developing wording to help explain randomisation to people being invited to participate in clinical trials. This work could be repeated and extended to other areas, to gather further ideas and suggested wording to explain randomisation to potential clinical trial participants. With a carefully thought through interactive workshop, healthcare consumers can contribute to developing wording to help explain randomisation to people being invited to participate in clinical trials. This could have wider use in clinical trials

Thank you