David Schaffer’s Commentary
Brief outline of my activities developing the BLIPS software system
Phase I – 1974-1977 The George Washington University, Washington DC
Thomas A. Ban, editor: ECDEU Manual on Documentation and Assessment Procedures for Clinical Trials in Neuropsychopharmacology. Second Edition (1983)
I served mainly as a programmer implementing the already-designed system, Biometric Laboratory Information System II (BLIPS II), where the "II" was meant to distinguish it from an earlier system (I). The main difference between I and II was that the set of psychiatric instruments (assessment forms) supported by BLIPS I was small (~6). BLIPS II expanded the basic set of instruments and also supported almost any new instrument that an investigator in the Early Clinical Drug Evaluation Unit (ECDEU) (Guy, 1976) network wanted to add.
The BLIPS II system supported a standard documentation for the data collected with each instrument in a clinical trial. The first step of the system's operation was the reading of the data sheets ("mark sense" optical scan paper forms), and the running of a battery of error detection algorithms, to insure data quality. Error reports were communicated back to each investigator as rapidly as possible, knowing that opportunities for retrieving missing/wrong data might be transient. Once a data set was declared ready-to-analyze, a standard set of algorithms was run including a complete listing of the raw data, summary statistics (means and variances), cross tabulations and finally Analysis of Variance (ANOVA) and a narrative summary.
My activities focused mainly on implementing the analysis scripts for all the supported instruments and troubleshooting any processing difficulties that arose in the day to day activities of the Lab.
The staff was about a dozen people including top management (e.g., Roland R. Bonato and William Guy), several statisticians (e.g., Kenneth Yang, Patricia A. Cleary), several data clerks responsible for processing the studies as rapidly as possible (investigators were always keen to have their results back ASAP so they could publish their findings), the software staff (Luis Aguilar and me), and the operators (Louis Napper) for the IBM system 360 computer that was devoted exclusively to BLIPS because of the sensitive nature of the data we processed. We used punch-card technology in those days. Remote cathode ray tube (CRT) terminals were not yet common and the personal computer lay in the future.
There were two main objectives for BLIPS: 1) to provide a rapid standard analysis of each clinical trial in the ECDEU network of investigators so that the investigators, FDA and NIMH could be assured of a standard view of emerging research into psychopharmacological compounds; and 2) to create a growing database that might support future research into larger questions than just the effect of one compound in one cohort. Such questions might involve investigating classes of compounds in a given disease cohort, or the investigation of the broad effects of a compound or class of compounds in multiple cohorts.
The decision was taken in 1977 by NIMH, the sole funding source for the Biometrics Lab, not to continue the project. At that point, I chose to follow Bill Guy to the Tennessee Neuropsychiatric Institute (TNI) in Nashville, TN, and continue my work with BLIPS.
Phase II – 1977-1980 Tennessee Neuropsychiatric Institute, Vanderbilt University, Nashville, TN
Here I assumed responsibility for what we called the Biometric Lab of TNI. Our group was responsible for the timely collection of all the assessments (data) from all the clinical research ongoing at TNI, (excluding a Pharmacology unit under Fridolin Sulser). I was also the "keeper of the blinds," so was on call 24-7 in case an adverse reaction to a study compound required breaking the blind.
I had brought the BLIPS II system with me and got it up and running on the University’s main computer, a Digital Equipment DEC-VAX machine. My first challenge was that the preprocessing software would not port successfully to the VAX and, besides, we didn’t use the "mark sense" forms. So, I rewrote the entire “preproc” adding a few new data quality checks in the process. During this time, Jerry Levine (our program manager at NIMH) was on sabbatical in Pisa, Italy, and struggling to get the BLIPS II system operating on their computers. The main stumbling block was also the “preproc.”
So, in Dec 1977, Levine supported my visit there. With the very capable assistance of a young programmer, Gabriele Massimetti, we were able to install my software and get the system running. Although Gabriele spoke no English and I spoke no Italian, with a combination of IBM Job Control Language, Fortran and arm-waving, we managed to work together. We were supported at the Clinica Psychiatria at the University of Pisa by Giovanni B. Cassano and Luciano Conti.
I continued development of TNI_BLIPS, adding more forms and some additional analyses to the standard package. These enhancements were responsible for a second visit to PISA in 1981 to share the software.
I had had high hopes for the TNI chapter in my life to provide opportunities for my engineering skills to be used for things like modeling mental functioning and malfunctioning. The teams there were diverse and the promise was great. However, after three years little research of the multidisciplinary sort developed; I realized that my plan was somewhat foolish. It was unrealistic to expect a productive academic research career without a PhD, so in the Fall of 1980 I left TNI to pursue my PhD in the Electrical and Biomedical Department at Vanderbilt.
September 21, 2017
H.E. LEHMANN, M. BERTHIAUME AND T.A. BAN, editors:
TRIMIPRAMINE: A NEW ANTI-DEPRESSANT
Montreal: Quebec Psychopharmacological Research Association; 1964 (105 pages).
Reviewed by Thomas A. Ban
INFORMATION ON CONTENTS: Trimipramine was synthesized, in 1956 by Jacob and Messer with the hope that it will combine the effect of imipramine on dysthymic mood and psychomotor inhibition with those of levomeprazine on states of anxiety and sleep disturbances. The synthesis resulted in trimipramine, a substance that differed pharmacologically from imipramine in that it reduced epinephrine-induced hypertension while increasing the hypertensive effect of norepinephrine. The psyhotropic properties of the substance were recognized and first evaluated in France, where the preclinical and clinical aspects of the drug were studied by Julou, Dutertre, Lambert, Sigwal, Vidal, Géraud, Millon and Pommé.
The material in this book is divided into two parts (Basic Science Session and Clinical Session), preceded by a Preface and followed by a Bibliography of publications on the drug. The Basic Science Session opens with Heinz E. Lehmann’s “Introduction”, in which he notes that the “issue of antipsychotic versus antidepressant pharmacotherapy has recently (1964) come under scrutiny” because there are psychotic non-depressed patients who improve when they receive antidepressant medication, and there is a certain proportion of depressed patients` who benefit from antipsychotic medication. He also expressed concerns about the lack of indicators for identifying those patients who will derive the greatest benefit from a particular psychoactive drug. Lehmann concludes his introduction as follows: “A more sophisticated diagnostic classification of our psychiatric patients has become an urgent requirement if we want to become closer to the ideal of good physicians who treat their patients as individuals and not statistical probabilities.” From the five papers that follow, in the first, the pharmacology of trimipramine is reviewed by Aurèle Beaulnes; in the second, the “Effects of trimipramine on capillary permeability alterations induced by dextran in the rat” are presented by L. Kato, B.Gozsy, M. Lemieux and A. St.Jean; in the third, the effects of the substance on the human electroencephalogram are discussed by Maurice Coulombe; in the fourth, the effects of trimipramine, levomepromazine and chlorpromazine on a battery of “psychophysical test performance” are compared by A. St.Jean, T.A. Ban and W. Noe; and in the fifth, the differential effects of trimipramine and chlorpromazine on spider web formation are described by G. Groh and M. Lemieux.
The Clinical Session opens with Pal Rajotte’s Introduction, in which he emphasizes the importance of establishing clearly the effectiveness of potential new antidepressants, in view of the experience that some of these drugs in clinical investigation had failed to fulfill expectations in terms of therapeutic effects. From the eight papers that follow, in two, one conducted by R. Legault and the other by R. Côté, the effects of trimipramine are described in 81 and 19 patient with anxiety and depression, respectively; and in another two, one conducted by Y Rouleau, and the other conducted by I. Erutku, T.A. Ban and H.E. Lehmann, the effects of the substance are discussed in 100 and 20 newly admitted depressed patients, respectively. In one paper, findings in two studies, both conducted in geriatric patients by H.E. Lehmann, V.A. Kral, T.A. Ban, H. Ast, C. Barriga and A Lidsky, are presented. From these two studies in one, the substance was used as add on medication in 10 patients, whereas in the other, a placebo-controlled study, the substance was used in 12 patients as sole medication. Finally, in two studies, one conducted by A. Scarlatesco, W. Jacob and L. Kelen in 129 patients, and the other by W Jacob in 102 patients, the effects of the substance were described in general practice.
The book concludes with a chapter by Thomas A. Ban on “Trimipramine in psychiatry,“ in which the history of trimipramine is briefly reviewed and the findings presented in the Basic and Clinical Sessions in this volume are integrated with the published literature.
EDITOR’S STATEMENT: Trimipramine: A New Anti-Depressant is based on the proceedings of the first North American Colloquium on Trimipramine, organized by the Quebec Psychopharmacological Research Association (QPRA) at St. Jean–de-Dieu Hospital, in Montreal-Gamelin, Quebec, Canada, on May 28, 1964. This was the second meeting of the QPRA. The first, held in January 1964, attempted to place a new group of drugs with anti-psychotic properties, the butyrophenones, in the proper place in the therapeutic arsenal of psychiatry. The goal of the second meeting was to introduce trimipramine, a substance already in clinical use in the treatment of depression in Europe at the time, in North America.
Thomas A. Ban
June 26, 2014