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Clinical trail design consideration in neuroscience research with trophic factors
276
Abstracts The two major components of the development process were (1) systematic examination of protein, phosphorus and kilocalorie values of food item portions using the HVH-CWRU Nutrient Data Base system to establish medians and ranges by food groups and (2) the ongoing collaboration with clinical center dietitians to determine food groups, food items, portion sizes, and format. The Food Exchanges for Meal Planning is composed of 11 food groups and 500 foods, and a computer system for meal planning using exchanges has been developed for patient counseling. In this presentation, the evaluation of precision, patient acceptability, and use for patient counseling in Phase II are discussed. Q u a l i t y Control for Dietary Data Collection in a Large Epidemiologic S t u d y Joan Hilner, Robert Birch, Arline M c D o n a l d , Linda Van H o r n , Bette Caan, Charlotte Bragg, a n d Marty Slattery University of Alabama at Birmingham, Birmingham, Alabama (P48) In epidemiologic studies, the need for valid and reliable dietary information necessitates emphasis on quality control (QC). CARDIA developed an extensive dietary history with stringent QC measures. These included a standardized interview format, centralized training/certification, a precoded form/data entry screen, and monitoring of form completeness and interview conduct. In addition, automated editing at data entry and error processing before nutrient data computation were performed. For accuracy of recorded information, a review of 153 audiotaped interviews found only 1.3 errors per tape in recording data and 2.7 errors per tape in the conduct of the interview. For completeness, a review of 14.1% of all forms found a mean error rate of 1.0% (1.71 errors in 171 responses) and of over 70,000 data items only 267 (0.4%) were missing. Thus, the QC measures used yielded high-quality dietary interview data.
Spirometry Quality Control in the C A R D I A S t u d y M a r y T o w n s e n d a n d L y n n e W a g e n k n e c h t for the C A R D I A S t u d y G r o u p
Division of Respiratory Disease Studies, Clinical Investigations Branch, Morgantown, West Virginia (P49) Collecting valid spirometric measurements requires attention to detail. To assure this, a stringent quality control program was developed for CARDIA. First, a manual of pulmonary function testing and a training videotape were developed that covered equipment maintenance and calibration, performance of the test, and maximum use of a microprocessor. Second, a central training course was conducted that stressed effective coaching, maintenance and calibration, and recognition and correction of technical and procedural problems. Third, each technician submitted four spirograms and calibration checks for certification. Fourth, 10% of the spirogram samples were submitted monthly for review and comments. These were also hand-measured by an experienced coder so that performance of the microprocessors could be continuously monitored. Fifth, site visits were conducted several months after the training course to observe testing techniques and to discuss problems. As a result of this program, more than 97% of the sample contained usable data.
Clinical Trial Design Consideration in Neuroscience Research with Trophic Factors Denis J. Petro a n d Frank C. D o r s e y
FIDIA Pharmaceutical Corp., Washington, D.C. (P50) Clinical research with Nerve Growth Factors and other biologic substances with trophic effects will inevitably follow the explosive growth in preclinical research with these substances. Clinical studies have been completed using a putative trophic substance, purified brain gangliosides (Cronassial) in a variety of neurologic disorders, including ALS, peripheral neuropathies, and retinitis pigmentosa. Negative studies have previously been reported in ALS and some chronic neuropathies such as Friedreich's ataxia and Charcot-Marie-Tooth disease. Positive results were obtained in Diabetic Neuropathy, AMN-ALD, and R.P. Instrumental and laboratory measures that demonstrate sensitivity to trophic factor effects are presented. Specific study design considerations pertinent to the demonstration of biologic properties of trophic substances include selection of (1) appropriate study patients, (2) length of study, (3) method of drug administration, and (4) measures of efficacy.
Abstracts
277
After approximately 400 patient-years, experience in clinical trials using Cronassial, the results both positive and negative, provide direction to further research with neurologic agents with trophic effects.
A Computerized Approach to Individualized Dietary Assessment, Education, and Counseling S a n d r a N. P o w e r s , C . M . Barnes, J.A. M a t s u m o t o , D.J. R a i z m a n , D.A. K u r t z m a n , and MDRD Study Group Vanderbilt University, Nashville, Tennessee (P51) Modification of Diet in Renal Disease (MDRD) Study is a multicenter prospective clinical trial requiring patients to adhere to a diet controlled in multiple nutrients. As the success of this clinical trial is largely dependent on adherence to diet prescription, a computerized approach is essential to provide the intensive education and long-term counseling required for a diet-related clinical trial. Dietary intake is documented by diet diaries and 24-hour recalls. Patients are educated primarily through the use of exchange lists and menus. For diet record analysis and menu planning, each clinical center uses a database that contains foods common to the patient population and pertinent nutrients. A subsetted, personalized database is created for each patient that contains only the foods preferred by the patient and allows creation of individualized exchange lists. Recipes are easily calculated and added to the patient's subsetted database. A spreadsheet format permits on-screen viewing of selected nutrient columns and the running total as foods are entered by name. Printed reports are customized by selecting options for style, format, and nutrient columns. Counseling is enhanced by providing immediate feedback and using "what-if" type analysis. The software is considered patient-friendly, thus permitting the patient to become an active participant in menu planning and intake assessment.
The Collection of Follow-up Data and Finding the Hard to Find J.M. Boswick, C.B. M c C a n t s , L.G. A r o n s o n , R.M. Califf, E.J. Topol, a n d the T A M I Study Group Duke University Medical Center, Durham, North Carolina (P52) When multicenter trials of coronary disease are performed, long-term follow-up is crucial to understanding the impact of different therapies. However, funding for such follow-up is often limited. Efficiency is enhanced by collection of baseline information concerning next of kin, workplace, an unrelated contact person, and family physician. The TAMI coordinating center has instituted a cost-efficient, automated follow-up system that provides each clinical center a complete 1-year follow-up kit. When mailed questionnaires are not returned, each clinical center staff telephones the patient. If these attempts fail, contact is attempted by the coordinating center. The National Death Index is used for the remaining patients. The 99% one-year follow-up rate from the TAMI trial indicates a multicenter trial can adequately track its patients by cost-efficient means.
Remote Monitoring of Clinic Performance Laurie L. Fitch, C h r i s t i a n T. C a m p o s , Paul F. Clarkson, a n d the P O S C H G r o u p University of Minnesota, Minneapolis, Minnesota (P53) POSCH has developed an extensive series of computer-generated reports to enable the coordinating center to monitor individual clinic performance. Included in these reports are the number of follow-up visits completed, missed, and overdue, the percentage completion rates for various laboratory tests and procedures, the percentage of forms received without error, the timeliness of the forms received, and the days lapsed since each patient was last in contact with the study. Other areas reviewed are the number of data corrections outstanding and a list of outstanding data forms. Each clinic is given copies of these reports, and the reports are discussed via telephone when necessary. In addition, summaries of the reports are utilized by the Data Monitoring Committee in their evaluation of clinic performance and adherence to protocol. The use of remote clinic performance monitoring enables POSCH to minimize expensive site visits to the clinics while ensuring adherence to protocol.
Abstracts The two major components of the development process were (1) systematic examination of protein, phosphorus and kilocalorie values of food item portions using the HVH-CWRU Nutrient Data Base system to establish medians and ranges by food groups and (2) the ongoing collaboration with clinical center dietitians to determine food groups, food items, portion sizes, and format. The Food Exchanges for Meal Planning is composed of 11 food groups and 500 foods, and a computer system for meal planning using exchanges has been developed for patient counseling. In this presentation, the evaluation of precision, patient acceptability, and use for patient counseling in Phase II are discussed. Q u a l i t y Control for Dietary Data Collection in a Large Epidemiologic S t u d y Joan Hilner, Robert Birch, Arline M c D o n a l d , Linda Van H o r n , Bette Caan, Charlotte Bragg, a n d Marty Slattery University of Alabama at Birmingham, Birmingham, Alabama (P48) In epidemiologic studies, the need for valid and reliable dietary information necessitates emphasis on quality control (QC). CARDIA developed an extensive dietary history with stringent QC measures. These included a standardized interview format, centralized training/certification, a precoded form/data entry screen, and monitoring of form completeness and interview conduct. In addition, automated editing at data entry and error processing before nutrient data computation were performed. For accuracy of recorded information, a review of 153 audiotaped interviews found only 1.3 errors per tape in recording data and 2.7 errors per tape in the conduct of the interview. For completeness, a review of 14.1% of all forms found a mean error rate of 1.0% (1.71 errors in 171 responses) and of over 70,000 data items only 267 (0.4%) were missing. Thus, the QC measures used yielded high-quality dietary interview data.
Spirometry Quality Control in the C A R D I A S t u d y M a r y T o w n s e n d a n d L y n n e W a g e n k n e c h t for the C A R D I A S t u d y G r o u p
Division of Respiratory Disease Studies, Clinical Investigations Branch, Morgantown, West Virginia (P49) Collecting valid spirometric measurements requires attention to detail. To assure this, a stringent quality control program was developed for CARDIA. First, a manual of pulmonary function testing and a training videotape were developed that covered equipment maintenance and calibration, performance of the test, and maximum use of a microprocessor. Second, a central training course was conducted that stressed effective coaching, maintenance and calibration, and recognition and correction of technical and procedural problems. Third, each technician submitted four spirograms and calibration checks for certification. Fourth, 10% of the spirogram samples were submitted monthly for review and comments. These were also hand-measured by an experienced coder so that performance of the microprocessors could be continuously monitored. Fifth, site visits were conducted several months after the training course to observe testing techniques and to discuss problems. As a result of this program, more than 97% of the sample contained usable data.
Clinical Trial Design Consideration in Neuroscience Research with Trophic Factors Denis J. Petro a n d Frank C. D o r s e y
FIDIA Pharmaceutical Corp., Washington, D.C. (P50) Clinical research with Nerve Growth Factors and other biologic substances with trophic effects will inevitably follow the explosive growth in preclinical research with these substances. Clinical studies have been completed using a putative trophic substance, purified brain gangliosides (Cronassial) in a variety of neurologic disorders, including ALS, peripheral neuropathies, and retinitis pigmentosa. Negative studies have previously been reported in ALS and some chronic neuropathies such as Friedreich's ataxia and Charcot-Marie-Tooth disease. Positive results were obtained in Diabetic Neuropathy, AMN-ALD, and R.P. Instrumental and laboratory measures that demonstrate sensitivity to trophic factor effects are presented. Specific study design considerations pertinent to the demonstration of biologic properties of trophic substances include selection of (1) appropriate study patients, (2) length of study, (3) method of drug administration, and (4) measures of efficacy.
Abstracts
277
After approximately 400 patient-years, experience in clinical trials using Cronassial, the results both positive and negative, provide direction to further research with neurologic agents with trophic effects.
A Computerized Approach to Individualized Dietary Assessment, Education, and Counseling S a n d r a N. P o w e r s , C . M . Barnes, J.A. M a t s u m o t o , D.J. R a i z m a n , D.A. K u r t z m a n , and MDRD Study Group Vanderbilt University, Nashville, Tennessee (P51) Modification of Diet in Renal Disease (MDRD) Study is a multicenter prospective clinical trial requiring patients to adhere to a diet controlled in multiple nutrients. As the success of this clinical trial is largely dependent on adherence to diet prescription, a computerized approach is essential to provide the intensive education and long-term counseling required for a diet-related clinical trial. Dietary intake is documented by diet diaries and 24-hour recalls. Patients are educated primarily through the use of exchange lists and menus. For diet record analysis and menu planning, each clinical center uses a database that contains foods common to the patient population and pertinent nutrients. A subsetted, personalized database is created for each patient that contains only the foods preferred by the patient and allows creation of individualized exchange lists. Recipes are easily calculated and added to the patient's subsetted database. A spreadsheet format permits on-screen viewing of selected nutrient columns and the running total as foods are entered by name. Printed reports are customized by selecting options for style, format, and nutrient columns. Counseling is enhanced by providing immediate feedback and using "what-if" type analysis. The software is considered patient-friendly, thus permitting the patient to become an active participant in menu planning and intake assessment.
The Collection of Follow-up Data and Finding the Hard to Find J.M. Boswick, C.B. M c C a n t s , L.G. A r o n s o n , R.M. Califf, E.J. Topol, a n d the T A M I Study Group Duke University Medical Center, Durham, North Carolina (P52) When multicenter trials of coronary disease are performed, long-term follow-up is crucial to understanding the impact of different therapies. However, funding for such follow-up is often limited. Efficiency is enhanced by collection of baseline information concerning next of kin, workplace, an unrelated contact person, and family physician. The TAMI coordinating center has instituted a cost-efficient, automated follow-up system that provides each clinical center a complete 1-year follow-up kit. When mailed questionnaires are not returned, each clinical center staff telephones the patient. If these attempts fail, contact is attempted by the coordinating center. The National Death Index is used for the remaining patients. The 99% one-year follow-up rate from the TAMI trial indicates a multicenter trial can adequately track its patients by cost-efficient means.
Remote Monitoring of Clinic Performance Laurie L. Fitch, C h r i s t i a n T. C a m p o s , Paul F. Clarkson, a n d the P O S C H G r o u p University of Minnesota, Minneapolis, Minnesota (P53) POSCH has developed an extensive series of computer-generated reports to enable the coordinating center to monitor individual clinic performance. Included in these reports are the number of follow-up visits completed, missed, and overdue, the percentage completion rates for various laboratory tests and procedures, the percentage of forms received without error, the timeliness of the forms received, and the days lapsed since each patient was last in contact with the study. Other areas reviewed are the number of data corrections outstanding and a list of outstanding data forms. Each clinic is given copies of these reports, and the reports are discussed via telephone when necessary. In addition, summaries of the reports are utilized by the Data Monitoring Committee in their evaluation of clinic performance and adherence to protocol. The use of remote clinic performance monitoring enables POSCH to minimize expensive site visits to the clinics while ensuring adherence to protocol.