Direct Information to At-risk Relatives

Summary

Participation Requirements

Description

This study is a multicenter open label, prospective randomized controlled superiority trial comparing an intervention of healthcare-assisted disclosure with standard care of family-mediated disclosure of hereditary cancer risk information in high-risk families in Sweden. SUBJECTS AND METHODS 600 pat...

This study is a multicenter open label, prospective randomized controlled superiority trial comparing an intervention of healthcare-assisted disclosure with standard care of family-mediated disclosure of hereditary cancer risk information in high-risk families in Sweden. SUBJECTS AND METHODS 600 patients/families will be enrolled and allocated in parallel to intervention or standard care. Patient data will be recorded in specialized case report forms (CRFs) designed according to best practice standards to minimize data errors. All subjects receive standard genetic counselling and information summarizing the results of their family investigation. They are informed about preventive measures when applicable, and are encouraged to inform their at-risk relatives (t=0). The intervention component is the addition of a healthcare-assisted disclosure procedure. Participants in the intervention arm will be offered the service of mailed letters directly to their at-risk relatives. If the participant approves the offer, letters will be sent to relatives who; have been identified by the participant and counsellor as a potential at-risk individual are eligible for surveillance or predictive testing and have not previously received written information about potential genetic cancer risk The direct letter will inform the at-risk relative that a cancer genetic investigation has been conducted in the family and the implications for him or her, and their blood relatives. To facilitate access to further information, contact details to the closest cancer genetics unit are included in the letter. The letters are sent with registered mail in neutral envelopes which means that recipients will have to show proof of identity to retrieve the letter from their local delivery service provider. METHODS FOR ASSESSMENT OF STUDY OUTCOMES For participants in both study arms, contact details of the at-risk relatives are identified in collaboration between health care provider and the participant. The health care provider records the name, approximate or exact year of birth and postal address of each at-risk relative for follow-up. At the time of follow-up (t=12 months) the research nurse will check whether the relatives, listed one year before, have contacted a Swedish cancer genetic unit. Primary outcome data is retrieved from the patient data registries at each clinic. The research nurse will also record additional data points from CRFs, enabling analysis of the other pre-specified outcome measures in the intervention arm. The outcome data are reported back to the national study secretariat as plain numbers without any personal details of the relatives. POWER CALCULATIONS AND ESTIMATION OF SAMPLE SIZE The participating study sites admit around 700 patients who meet the inclusion criteria each year. A modest assumption is that half of them will accept an invitation to enroll in the study. A statistical calculation estimate that 600 patients/families need to be included to generate a sufficiently large study population. The primary outcome measure (in total and for subgroups based on family diagnosis, gender and age) is the proportion of at-risk relatives per family who approach a cancer genetic unit for counselling within 12 months. If three out of four relatives contact a cancer genetic unit in one study arm (e.g. intervention) and two out of four does so in the other study arm (e.g. control/standard care) then the study have a power of >0.999 to discover a difference in effect between the two protocols. If instead one extra at-risk relative in every second family approaches a cancer genetic unit in one of the study arms, the power is 0.87. Regarding the diagnose-specific subgroup analysis it is expected that around 220 patients will be recruited in the two familial cancer diagnosis groups (power=0.97) and around 130 in the group with hereditary breast and ovarian cancer syndromes (power=0.85). In the smallest group with Lynch syndrome patients, only around expect 30 patients is expected to be included after 28 months at normal patient influx. Thus, this group will be too small, and power subsequently too low, to motivate subgroup specific analysis (power=0.30). Concerning the subgroup analyses for gender and age the study will have a power between 0.96 and 0.99 to discover differences between the intervention and the control groups, if three instead of two at-risk relatives approach a cancer genetic unit within a year. STATISTICAL ANALYSIS PLAN OF MAIN STUDY See attached document SAP, Table 1. INTERNAL PILOT As this protocol has never been tested in Swedish clinical practice an internal pilot phase is included in the outline of the project. Internal pilot point (IPP) is set to the time when 20 individuals in total (across the 3 pilot study sites) have been included in the study, allocated to study arms, and have been treated according to protocol. At IPP the pilot outcomes will be evaluated (see attached document SAP, Table 2). Continuation of the full-powered study will be determined by considering the progression criteria filled, the potentially necessary amendments, and the degree of which the amendments deviate from the original piloted study protocol.

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