HEPATOCELLULAR TRANSPLANTATION AND TARGETING GENETIC MARKERS TO HEPATIC CELLS 
technique had been previously investigated by Dr. Rosenberg and his colleagues and shown 
to induce responses to 38% of patients and complete responses in 10%. The initial 
approval for this protocol by the Recombinant DNA Advisory Committee carried the 
stipulation that "The patients selected will have a life expectancy of no more than 90 
days" (Recombinant DNA Advisory Committee, 1989). (In fact, suirvival of some patients 
has been considerably better with one patient having a complete remission to almost 2 
years.) The present protocol is not different in this regard from the ADA gene therapy 
protocol of Blaese et al which involves pediatric subjects with a good prognosis for 
long term survival. 
While the need for long-term follow-up is readily apparent, in practice it is 
frequently difficult to engage patients in long-term studies. In general, it is the 
experience of clinical investigators that the critical issue in obtaining long-term 
cooperation of study subjects is to establish a strong relationship between the patients 
and their families and various health care professionals including physicians, nurses, 
social workers, and psychologists. Several strategies will be employed as part of this 
protocol to establish long-term follow-up. These strategies will include: a) 
identifying individual physicians, nurses, social workers, and psychologists as primary 
contacts at TCH; b) identifying the GCRC and GCRC staff as the central focus of health 
care and clinical research; c) involving primary care physicians from the patient's 
community (often hundreds of miles from Houston) in the delivery of clinical follow- 
up; d) involving patients and their families in ongoing psychosocial counselling and 
evaluation (see below); e) emphasizing the importance of long-term follow-up to patients 
and their families during the process of informed consent and g) retaining the option 
to consult with child protective services if the withdrawal of a child from follow-up 
after HCT is performed is thought to endanger the well-being of the child. In addition, 
we will be proposing the creation of a "registry" for tracking patients following gene 
transfer trials in collaboration with Dr. W. French Anderson (NIH) , Susan Mize (Mize 
Information Enterprise Inc - currently director of the Register of Selected Inherited 
Metabolic Disorders), Dr. Baruch Brody (BCM) , and Dr. Claudia Kozinetz (BCM) . We feel 
that a formal registry is important to ensure that patients (particularly minors) are 
not lost to follow-up and that their health care providers receive updated information 
about recommended surveillance, diagnostic, or therapeutic interventions that may be 
indicated. 
A psychosocial protocol has been implemented which will provide for a longitudinal 
evaluation of patients treated with gene transfer. This study will address the ability 
of patients and families to participate in long-term follow-up and identify factors 
which will contribute to consistent follow-up (Ledley, Mikhail, and Schwartz, 
Psychosocial Issues in the Clinical Application of Somatic Gene Therapy, submitted). 
iii) It is a statutory principle of clinical research for the patient to have 
sufficient knowledge to make an informed decision about participating in clinical 
research and provide a meaningful informed consent (Surgeon General, 1966; Code of 
Federal Regulations, 1983; Andrews, 1987). Obtaining a meaningful informed consent, 
however, is difficult. It has been repeatedly demonstrated that patients retain only 
a fraction of the information provided by physicians. In some studies only three- 
Recombinant DNA Research, Volume 14 
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