PHAROSSafetyAbstract

SAFETY AND FEASABILITY OF THE PROSPECTIVE HUNTINGTON AT RISK OBSERVATIONAL STUDY:

A PRELIMINARY REPORT

Presenting Author: Elise P. Kayson, Rochester, NY, and the Huntington Study Group/PHAROS Investigators

Objective: The Prospective Huntington At Risk Observational Study (PHAROS) was developed to determine the safety, feasibility and design for future controlled therapeutic trials aimed at delaying the clinical onset of Huntington’s Disease (HD) in unaffected (presymptomatic) individuals.

Background: Relatively little is known about the approximately 97% of adults in the US who are at immediate risk to develop HD and who have chosen not to undergo presymptomatic predictive testing, yet are willing to participate in research. PHAROS is the first study to systematically, examine a cohort of adults at risk for HD in order to determine prospectively the clinical onset of the earliest clinical precursors of HD and the safety and feasibility of preventive therapeutic trials.

Design/Methods: PHAROS was initiated by the Huntington Study Group (HSG) in July 1999 with a target to enroll 1000 eligible research participants including unaffected adults, 30-55 years old, who: 1) have (had) a parent affected by HD, 2) have not undergone presymptomatic predictive DNA testing for the HD gene and wish to remain unaware of their gene status, but nonetheless, 3) consent to provide a coded blood sample for confidential (double-blinded) analysis of their DNA for the HD gene, and 4) undergo comprehensive clinical evaluations about every 9 months over a minimum 3-year period of observation. PHAROS investigators are asked to report relevant cohort events and adverse experiences within 3 days of their detection. Reports are reviewed and classified by the PHAROS Ethics and Steering Committees.

Results: As of November 2001, 673 eligible PHAROS research participants have been enrolled at 43 participating sites in the US and Canada and have been followed for a mean observation period of 1.24 [plus/minus] 0.73 (mean [plus/minus]sd)years. Fifty cohort events have been reported involving 43 (6.4%) research participants, including 9 (1.3%) who withdrew participation in PHAROS; 2 (0.3%) who died (1 accident, 1 stroke); 13 (1.9%) who were hospitalized for medical reasons (3 for routine childbirth); 12 (1.8%) who developed new-onset depression; 9 (1.3%) who required a new evaluation by a mental health professional; 2 (0.3%) who participated in another genetic research study and 1 (0.1%) who was administered a neuroleptic medication. No participant reported a breach of confidentiality in disclosure of HD gene status.

Conclusions: Thus far, the overall number of cohort events is in keeping with our expectations, including our projected 5% annual rate of participant withdrawal of consent for research involvement in PHAROS. The 1.4% annual incidence of new-onset depression is also consistent with the 1.6% annual incidence reported in a general medical population (J Fam Practice 49:68-72, 2000). Our preliminary experience indicates that PHAROS is a safe and feasible research undertaking, but continued care and vigilance are required to protect the welfare of this unique and potentially vulnerable research population.

Study supported by: The Huntington’s Disease Society of America, the Hereditary Disease Foundation and the Huntington Society of Canada.


H · S · G Huntington · Study · Group


SAFETY AND FEASABILITY OF THE PROSPECTIVE HUNTINGTON AT RISK OBSERVATIONAL STUDY: A PRELIMINARY REPORT Presenting Author: Elise P. Kayson, Rochester, NY, and the Huntington Study Group/PHAROS Investigators Objective: The Prospective Huntington At Risk Observational Study (PHAROS) was developed to determine the safety, feasibility and design for future controlled therapeutic trials aimed at delaying the clinical onset of Huntington’s Disease (HD) in unaffected (presymptomatic) individuals. Background: Relatively little is known about the approximately 97% of adults in the US who are at immediate risk to develop HD and who have chosen not to undergo presymptomatic predictive testing, yet are willing to participate in research. PHAROS is the first study to systematically, examine a cohort of adults at risk for HD in order to determine prospectively the clinical onset of the earliest clinical precursors of HD and the safety and feasibility of preventive therapeutic trials. Design/Methods: PHAROS was initiated by the Huntington Study Group (HSG) in July 1999 with a target to enroll 1000 eligible research participants including unaffected adults, 30-55 years old, who: 1) have (had) a parent affected by HD, 2) have not undergone presymptomatic predictive DNA testing for the HD gene and wish to remain unaware of their gene status, but nonetheless, 3) consent to provide a coded blood sample for confidential (double-blinded) analysis of their DNA for the HD gene, and 4) undergo comprehensive clinical evaluations about every 9 months over a minimum 3-year period of observation. PHAROS investigators are asked to report relevant cohort events and adverse experiences within 3 days of their detection. Reports are reviewed and classified by the PHAROS Ethics and Steering Committees. Results: As of November 2001, 673 eligible PHAROS research participants have been enrolled at 43 participating sites in the US and Canada and have been followed for a mean observation period of 1.24 [plus/minus] 0.73 (mean [plus/minus]sd)years. Fifty cohort events have been reported involving 43 (6.4%) research participants, including 9 (1.3%) who withdrew participation in PHAROS; 2 (0.3%) who died (1 accident, 1 stroke); 13 (1.9%) who were hospitalized for medical reasons (3 for routine childbirth); 12 (1.8%) who developed new-onset depression; 9 (1.3%) who required a new evaluation by a mental health professional; 2 (0.3%) who participated in another genetic research study and 1 (0.1%) who was administered a neuroleptic medication. No participant reported a breach of confidentiality in disclosure of HD gene status. Conclusions: Thus far, the overall number of cohort events is in keeping with our expectations, including our projected 5% annual rate of participant withdrawal of consent for research involvement in PHAROS. The 1.4% annual incidence of new-onset depression is also consistent with the 1.6% annual incidence reported in a general medical population (J Fam Practice 49:68-72, 2000). Our preliminary experience indicates that PHAROS is a safe and feasible research undertaking, but continued care and vigilance are required to protect the welfare of this unique and potentially vulnerable research population. Study supported by: The Huntington’s Disease Society of America, the Hereditary Disease Foundation and the Huntington Society of Canada. Neurology, Vol.58, Number 7, Suppl 3, 2002

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