The following details are presented in accordance with the CONSORT reporting guidelines for randomised trials of non-pharmacologic treatment . The following Human Research Ethics Committees in Victoria, Australia have all approved this project: Austin Health, Bendigo Health, Ballarat Health, Royal Childrens Hospital, Melbourne Health and Southern Health.
Potential participants for this prospective, randomised controlled trial must:
be the first person in a family to be diagnosed, or have a child diagnosed, with a genetic condition about which the genetic information has implications for other family members and for which genetic testing or diagnosis based on clinical information is possible
be able to speak, read and write English
have at least one at-risk relative who resides in Victoria
be aged 18 years or over.
Potential participants are excluded if they:
have a cognitive disorder that affects their ability to give informed consent
have received a diagnosis during pregnancy
reside outside of Victoria.
Setting and locations
The trial is being conducted within genetic clinic settings at six tertiary public hospitals in Victoria. These sites were chosen on the basis of variation in client populations and types of genetic diagnoses likely to be made, as well as the presence of an experienced genetic counsellor on staff.
Genetic counsellors performing the intervention
The 10 genetic counsellors in the study routinely disclose new genetic information to probands as part of their clinical duties. Each genetic counsellor is either fully certified or has a minimum of two years clinical experience. All counsellors have undertaken specific training in delivering the genetic counselling intervention and have access to an intervention protocol manual.
Development of the intervention was informed by a framework for complex interventions . This enabled the intervention to incorporate the patient-centred ethos and nondirective stance fundamental to genetic counselling practice with a process that is standardised and can be replicated. The intervention was designed to use genetic counselling strategies to address documented personal barriers to family communication. The Reciprocal Engagement Model  is the model of genetic counselling practice applied in the intervention, while evidence for barriers was taken from a systematic literature review .
The counselling framework for the intervention has three domains; the focus on each is determined by the participant’s needs over time. These are:
“Getting the picture” about the participant’s experiences of communication to date, including: which relatives have been informed and their responses; recognising and exploring the conscious and unconscious barriers to communication; supporting adjustment of the participant to their own genetic status.
Forming an intention to act. This includes maintaining or enhancing the participant’s capacity for communication; facilitating decision-making; and resolving ambivalence.
Planning to act. Here the participant intends to communicate, options are elicited, a plan developed and potential scenarios explored to prepare the participant.
The intervention was designed to be feasible to implement in clinical practice, as an adjunct to usual care .
To further emulate the ‘real world setting’ the intervention is delivered by the same genetic counsellor that each participant met at their visit to the genetics clinic.
Intervention phone calls are audiotaped and analysed to examine adherence to the intervention protocol. Such monitoring of the intervention fidelity ensures its delivery and receipt is as intended.
At the time of their initial genetic consultation all probands receive standard care concerning family communication from the genetic counsellor. This generally involves a discussion of possible implications for other family members and the offer of explanatory letters for the proband to pass on to at-risk relatives Probands are informed about the research study by the genetic counsellor at the end of this consultation. If they consent, their contact details are faxed to the research team for recruitment to proceed. A researcher then contacts potential participants by telephone to explain the project and the possibility that they may receive follow-up telephone calls (if in the intervention arm). Written informed consent is requested by mail and, once received, participants are randomised into the intervention or control group.
Participants who are randomised into the control group receive no further contact specific to family communication.
Participants in the intervention group receive standard care plus three intervention phone calls from a genetic counsellor delivered over the subsequent 12 months.
Primary – measurement of uptake of genetic services
The number of at-risk relatives is ascertained from three generation pedigrees collected by the genetic counsellors at the time of diagnosis for all participants and held in the family Genetics Files. Eighteen months after the proband attends the genetic clinic and is enrolled in the study, the family file is audited to determine the actual number of at-risk relatives who make contact with Victorian genetic clinics.
The total number of at-risk relatives who have contact with a genetics service divided by the total number of at-risk relatives gives a percent that can be compared between the two arms of the study. A person’s ‘at-risk status’ is based on genetic relatedness, taking into account the inheritance pattern for the condition involved. During the study there may be further clarification of the at-risk status. For example, a negative genetic test result for an autosomal recessive condition in one family member means that the mutation will not be further transmitted in that branch of the family. Therefore, the original estimate of the number of ‘at-risk’ relatives will be reduced accordingly. Relatives who live overseas or interstate are excluded from the analysis as we are unable to document their uptake of genetics services.
All data are managed in ACCESS database, 2007 version.
Secondary – follow-up telephone interview to assess participant experiences
At the 18 month exit point of the study, participants are telephoned to complete a structured survey assessing their experiences of family communication and participation in a RCT. This identifies differences in attitudes, awareness and suggestions for best practice between the two groups. This survey has been developed using a Delphi process involving the study team and both experienced and student genetic counsellors. It focuses on:
awareness of the importance of information for at-risk family members
experience of informing family members
which family members were informed and when
the barriers and facilitators to communication
professional support that is helpful and acceptable to families
other suggestions for practice.
In addition, the genetic counsellors who delivered the intervention will be interviewed in a focus group setting to reflect on their experience of participation.
A further sub-study to assess fidelity will examine the intervention phone calls to determine counsellors’ adherence to the intervention protocol.
We aim to detect a difference of at least 15% in contact with a genetic service (e.g. 20% of relatives in the control group, 35% in the intervention group). A sample size of 151 at-risk relatives per group has 80% power to detect this difference (with an alpha level of 0.05) if all the at-risk relatives were independent of each other; that is, if the clustering of at-risk relatives is ignored. Data from a preliminary study in Tasmania suggest that there is an average of seven at-risk relatives per proband. With a conservative estimate of five at-risk relatives per proband, a sample size of 151 at-risk relatives requires participation of 30 probands .
Since is it probable that responses of at-risk relatives of each proband are more similar to each other than to relatives of other probands, the clustering effect must be taken into account. The average degree of similarity to be expected between at-risk relatives of a given proband (the intraclass correlation (ICC) is unknown as there have been no similar studies. Data from community-based surveys in the UK have shown that many ICCs for households were in the range of 0.0 to 0.3 . Assuming an ICC of 0.25 and an average cluster size of 5, the Design Effect (DE) would be 2 (DE = 1+ (cluster size -1)*ICC). Thus, the required number of at-risk relatives in each group is 302 (=151*2) necessitating a sample size of 60 probands in each arm. Given our conservative assumption of five at-risk relatives per proband, this will detect a difference of at least 15%. In addition, with attrition rate of approximately 15% over the 18 month study period, there is a need to recruit an extra 10 probands for each arm (i.e. 70 probands per arm).
To allow for correlation between the likelihood of making contact with a genetics service of relatives of the same probands, the method of marginal logistic regression models fitted using Generalised Estimating Equations (GEEs) with information sandwich estimates of standard error will be used to estimate the odds ratios between the intervention and control arm for the primary outcome.
The randomisation sequence was constructed by the Clinical Epidemiology and Biostatistics Unit (CEBU) at the Murdoch Childrens Research Institute using Stata 11.0 (StataCorp, College Station, TX) statistical software. A statistician in CEBU, who is independent of the study investigators, retains the only copy of the randomisation sequence, Randomisation is stratified by genetic counsellor, allocation is 1:1 and random block sizes are used to ensure concealment of allocation. After a participant is enrolled in the study, the study co-ordinator contacts CEBU to obtain the treatment allocation for that participant.