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Background and Methods In 1987 we began a multicenter controlled clinical trial of deprenyl (a monoamine oxidase inhibitor) and tocopherol (a component of vitamin E that traps free radicals) in the treatment of early Parkinson's disease. We randomly assigned 800 patients to one of four treatments: placebo, active tocopherol and deprenyl placebo, active deprenyl and tocopherol placebo, or both active drugs. The primary end point was the onset of disability prompting the clinical decision to begin administering levodopa. An interim analysis showed that deprenyl was beneficial . We report the results of tocopherol treatment after a mean (±SD) follow-up of 14 ±6 months, as well as the follow-up results for deprenyl.
Results There was no beneficial effect of tocopherol or any interaction between tocopherol and deprenyl. The beneficial effects of deprenyl, which occurred largely during the first 12 months of treatment, remained strong and significantly delayed the onset of disability requiring levodopa therapy (hazard ratio, 0.50; 95 percent confidence interval, 0.41 to 0.62; P<0.001). The difference in the estimated median time to the end point was about nine months. The ratings for Parkinson's disease improved during the first three months of deprenyl treatment; the motor performance of deprenyl-treated patients worsened after the treatments were withdrawn.
Conclusions Deprenyl (10 mg per day) but not tocopherol (2000 IU per day) delays the onset of disability associated with early, otherwise untreated Parkin-son's disease. The action of deprenyl that accounts for its beneficial effects remains unclear.
-Tocopherol, a biologically active component of vitamin E, attenuates the effects of lipid peroxidation by trapping free radicals4,5. The multicenter controlled clinical trial Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) was carried out to determine whether long-term therapy with deprenyl or tocopherol would extend the length of time before advancing disability requires the initiation of levodopa therapy in patients with early, untreated Parkinson's disease1. An interim analysis of this trial, prompted by independent monitoring and based on the observation of 800 patients for a mean (±SD) of 12 ±5 months, indicated that deprenyl reduced the risk of disability requiring levodopa therapy by approximately 50 percent6. However, it was unclear whether the effects of deprenyl would be sustained or whether deprenyl resulted in short-term amelioration of clinical features (symptomatic effect), a slowing of underlying nigral degeneration (protective effect), or both mechanisms. This report extends the analysis of the DATATOP clinical trial to include 14 ±6 months of observation and a modification of the protocol based on the interim analysis, and addresses the independent and interactive effects of tocopherol and deprenyl.
Methods
The methods used in the DATATOP trial, including a description of the design, organization, recruitment of subjects, data acquisition and management, statistical methods, and interim results, have been reported in detail elsewhere1,6 and are summarized below.
Enrollment and Follow-up
Eight hundred untreated patients who had had Parkinson's disease (stage I or II) for less than five years and who met other eligibility criteria1 were enrolled between September 3, 1987, and November 15, 1988. They were randomly assigned according to a two-by-two factorial design7 to one of four treatment groups: tocopherol placebo and deprenyl placebo; tocopherol (2000 IU per day) and deprenyl placebo; deprenyl (10 mg per day) and tocopherol placebo; and deprenyl (10 mg per day) and tocopherol (2000 IU per day). The process of randomization was designed to ensure that each investigator had an approximate numerical balance of subjects in the four groups6. The subjects took 1000-IU capsules of racemic dl--tocopherol or identical-appearing placebo capsules (Hoffmann-LaRoche, Nutley, N.J.) and 5-mg tablets of l-deprenyl or identical-appearing tablets of placebo (Somerset Pharmaceuticals, Tampa, Fla.) twice daily with morning and evening meals.
The subjects were reevaluated 1 month and 3 months after randomization and approximately every 3 months thereafter, for a planned maximum of 24 months of follow-up. At each visit, the subjects were evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS), including its motor, mental, and activities-of-daily-living components8. Evaluation with the Hamilton Depression Scale9 was carried out at base line, at one and three months, and at six-month intervals thereafter. The procedures for monitoring surveillance laboratory tests and compliance are described elsewhere1,6.
End Points
The primary end point of the trial occurred when, in the judgment of the enrolling investigator, a subject reached a level of functional disability sufficient to warrant the initiation of levodopa therapy1. Thereupon, the experimental treatments were withdrawn and investigators and subjects were kept unaware of the treatment assignments; the subjects underwent final evaluations approximately 30 days later.
Modification of the Protocol
An independent monitoring committee recommended (February 11, 1989) an interim analysis6 of the effect of deprenyl, which included follow-up data obtained through May 20, 1989, when investigators were first informed of the interim results. The subjects were first advised of the interim findings after their scheduled follow-up visits conducted between July 31, 1989, and December 19, 1989.
All actively participating subjects who had not reached the primary end point provided informed consent for the modification of the trial that followed the interim analysis. Under the revised protocol, additional follow-up evaluations of these subjects were performed approximately one and two months after experimental treatments were withdrawn by tapering the dosages over a one-week period. Treatment with deprenyl (10 mg per day) could be started during the two months after treatment was withdrawn if the investigator determined that features of Parkinson's disease had worsened sufficiently as a consequence of the withdrawal of experimental treatments. All subjects, coordinators, and investigators were kept unaware of the treatment assignments throughout this modified phase of the trial.
Statistical Analysis
In accordance with the intention-to-treat principle,10 statistical analyses included all 800 subjects who were randomly assigned to the four treatment groups. All P values were two-tailed. The primary analysis used methods for evaluating survival11 to account for the varying lengths of follow-up among subjects who reached the end point, those who withdrew from the trial before reaching the end point, and those still being followed who had not reached the end point. The cumulative probabilities of reaching the end point were estimated with the method of Kaplan and Meier12; data on subjects who withdrew from the study were censored as of their date of withdrawal. The end-point comparisons used Pearson's chi-square statistic,13 the stratified log-rank test,14 and Cox's proportional-hazards regression model,15 with the identity of the participating investigator entered as a stratification factor. The risk among subjects receiving an active treatment (deprenyl or tocopherol), relative to that among subjects not receiving that treatment, was expressed as a hazard ratio -- that is, the ratio of the risk per unit of time until the end point was reached among subjects assigned to active treatment to the corresponding risk among subjects not assigned to that treatment.
The differences among the four treatment groups with respect to adverse effects reported after base line were evaluated by chi-square statistics13. The rates of disease progression and the changes in the scores of the UPDRS and the Hamilton Depression Scale were evaluated by analysis of variance,13 with adjustment for investigator effects. Follow-up variables were analyzed to determine the main effects of deprenyl and tocopherol as well as interactions between these drugs.
Results
Comparability of Treatment Groups and Adverse Events
The four treatment groups did not differ significantly in the variables measured at base line, including age, sex, ratings on the UPDRS and Hamilton Depression Scale, any previous levodopa treatment, time from the onset of illness to randomization, level of education, and employment status.
The occurrence of adverse symptoms, other medical conditions, and abnormal laboratory results was generally infrequent and uniform among all treatment groups. Of the 63 symptoms of moderate or serious severity reported to have occurred at least once, regardless of any perceived relation to experimental treatments or Parkinson's disease, only nausea occurred disproportionately (in one subject taking placebo only, none taking tocopherol and placebo, two taking deprenyl and placebo, and six taking both drugs; nominal P = 0.045, deprenyl).
Of the 17 other medical conditions reported to have occurred at least once, regardless of any perceived relation to the experimental treatments or Parkinson's disease, only musculoskeletal injuries and cardiac arrhythmias occurred disproportionately (injuries in 5 subjects taking placebo only, 6 taking tocopherol and placebo, 18 taking deprenyl and placebo, and 11 taking both drugs; nominal P = 0.007, deprenyl; arrhythmias: 1 subject taking placebo, none taking tocopherol and placebo, 4 taking deprenyl and placebo, and 4 taking both drugs; nominal P = 0.045, deprenyl). The cardiac arrhythmias were not considered life-threatening and included increased premature ventricular contractions (one subject taking placebo only and one taking both drugs), supraventricular tachycardia (one taking deprenyl and placebo and one taking both drugs), and bradycardia with varying degrees of atrioventricular block (three taking deprenyl and placebo and two taking both drugs). No significant treatment-related changes in blood pressure or pulse recordings were found during the study.
Of the clinically important laboratory abnormalities found on the battery of 41 surveillance tests, only abnormal elevation of serum aminotransferase levels was found to be a significant treatment effect. Aspartate aminotransferase levels exceeding 36 U per liter in men and 34 U per liter in women occurred in 10 subjects taking placebo only, 3 taking tocopherol and placebo, 20 taking deprenyl and placebo, and 8 taking both drugs (P = 0.028, deprenyl; and P = 0.005, tocopherol); alanine aminotransferase levels exceeding 43 U per liter in men and 34 U per liter in women occurred in 10 subjects taking placebo only, 4 taking tocopherol and placebo, 24 taking deprenyl and placebo, and 7 taking both drugs (P = 0.016, deprenyl; and P = 0.001, tocopherol). Elevations of alanine aminotransferase levels exceeding 150 percent of base-line values on more than one follow-up visit were found in only two subjects (one taking deprenyl and placebo and one taking both drugs). Adverse events prompted emergency disclosure of the treatment assignments of two subjects (one taking deprenyl and placebo and one taking both drugs) in whom cancer developed and one subject taking both drugs who had hallucinations. No subjects died while participating in this phase of the study.
Compliance in taking experimental medications was excellent among all treatment groups. The overall compliance rate, as a percentage of the doses dispensed that were actually taken, ranged from 97.9 to 99.5 percent for both tocopherol and deprenyl. The results of urine testing for amphetamine and methamphetamine during the follow-up visits agreed well with the treatment assignments, ranging from 95 to 100 percent agreement among subjects not assigned to deprenyl and from 86 to 95 percent among those assigned to deprenyl. The distribution of serum tocopherol concentrations exceeding 2.0 mg per deciliter (46 µmol per liter) during the follow-up visits also matched the treatment assignments, ranging from 81 to 100 percent agreement among subjects not assigned to tocopherol and from 78 to 90 percent among those assigned to tocopherol.
End Points
Table 1 compares the status according to treatment group, as of the last evaluation during experimental treatments, of the 376 subjects who reached the primary end point, the 57 subjects who withdrew from the study before reaching the end point, and the 367 subjects who were still being followed and had not reached the end point.
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Kaplan-Meier plots (Figure 1) of the probability of reaching the end point of the study differed significantly between subjects assigned to deprenyl (with placebo or tocopherol) and those not assigned to deprenyl (those taking placebo alone or placebo and tocopherol) (hazard ratio, 0.50; 95 percent confidence interval, 0.41 to 0.62; P<0.001). The projected median lengths of time to reach the end point were 719 days for the subjects who were assigned to deprenyl and 454 days for the subjects who were not assigned to deprenyl, representing an approximate difference of almost 9 months.
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The 367 subjects who did not reach the end point were withdrawn from experimental treatments and evaluated approximately one and two months later. During the two months after treatment was withdrawn, 4 subjects (2 taking double placebo, 1 taking tocopherol and placebo, and 1 taking deprenyl and placebo) reached the primary end point, 1 taking both drugs left the trial, and 52 were judged by the investigator to have an increase in the severity of Parkinson's disease and were given deprenyl. There was no evidence of differences among the treatment groups in the rate of early deprenyl administration (12 of 72 subjects taking double placebo, 17 percent; 13 of 77 taking tocopherol and placebo, 17 percent; 19 of 110 taking deprenyl and placebo, 17 percent; and 8 of 108 taking both drugs, 7 percent; P = 0.12).
Secondary Response Variables
Table 2 shows the average rate of decline from base-line values for the UPDRS variables in all subjects completing at least a six-month evaluation, regardless of whether they reached the end point. There were no significant differences in the rate of change in secondary response variables between subjects assigned to tocopherol and those not assigned to tocopherol. The average rate of decline in all UPDRS variables was significantly slower in subjects taking deprenyl (with placebo or tocopherol) than in subjects not taking deprenyl (those taking placebo alone or tocopherol and placebo).
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Table 3 shows the changes in the ratings on the UPDRS and Hamilton Depression Scale from base line in all subjects who completed follow-up evaluations after one and three months. Significant changes during the first three months of treatment (the "wash-in" period) favoring the subjects taking deprenyl occurred in all UPDRS variables at one and three months. No significant short-term changes in UPDRS ratings were found that favored the subjects taking tocopherol.
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Among the subjects who did not reach the end point and who were withdrawn from experimental treatments in accordance with the modification of the trial protocol, slight worsening of the motor component of the UPDRS was found one month (P = 0.042) and two months (P<0.001) after the withdrawal of treatments in the subjects assigned to deprenyl as compared with the subjects not assigned to deprenyl (Table 3). The disproportionate worsening of motor performance was largely attributable to changes in scores for tremor and rigidity. There were no significant treatment-related effects due to withdrawal on the mental or activities-of-daily-living components of the UPDRS or on the Hamilton Depression Scale.
Discussion
Effects of Tocopherol on Primary and Secondary Response Variables
Our clinical trial revealed no evidence of any beneficial effect of -tocopherol (2000 IU per day) in either slowing functional decline or ameliorating the clinical features of Parkinson's disease. The failure of tocopherol to influence the progression of Parkinson's disease in this study does not preclude the potential effectiveness of other antioxidants. Treatment with tocopherol, which traps peroxyl radicals and interrupts the chain reaction of lipid peroxidation, may be less effective than interventions that prevent the formation of cytotoxic radicals and the initiation of lipid peroxidation5. It is also possible that inadequate amounts of tocopherol accumulated in the central nervous system in our subjects.
Effects of Deprenyl on Primary and Secondary Response Variables
Our previous findings of a substantial benefit of deprenyl in delaying the onset of disability associated with Parkinson's disease have been confirmed by the findings in this extended period of observation. The results translate into a delay of almost nine months in the development of disability requiring levodopa therapy. These benefits were associated with a slight improvement in motor performance after deprenyl treatment was begun and a slight worsening after it was withdrawn. The benefits of deprenyl with respect to the primary end point of disability were found in all subjects regardless of their base-line characteristics and are supported by a slowing of the rate of decline of the UPDRS scores (Table 2). The effect of deprenyl on all response variables was the same among patients who received tocopherol and those who did not.
Mechanisms of Deprenyl Effects
Our data support our previous findings that deprenyl is well tolerated and slows the functional decline of otherwise untreated subjects with early Parkinson's disease. The pattern of the survival curves comparing subjects who received deprenyl with those who did not receive it showed initial sharp divergence followed by approximately constant separation. Our extended observations, which included a two-month period without treatment, indicate that deprenyl produces a slight but sustained improvement in the clinical ratings of Parkinson's disease.
The improvement in the UPDRS scores after the initiation of deprenyl and the worsening of the UPDRS motor scores during the two months after withdrawal (Table 3) suggest that the observed benefit of deprenyl in delaying disability is partly related to a symptomatic amelioration of Parkinson's disease. On the other hand, the superior survival with respect to the primary end point even among deprenyl-treated subjects who initially had no improvement in total UPDRS scores (Figure 2) and the overall persisting benefit (as compared with base-line status) among deprenyl-treated subjects who did not reach the end point and who did not require deprenyl during the two months after withdrawal (Table 2) suggest a protective influence. There was no evidence that deprenyl had appreciable antidepressant effects during this extended period of observation.
Uncontrolled studies suggest that deprenyl may increase the life span of patients with advanced Parkinson's disease18,19 and retard the death of nigral neurons20. The design of our clinical trial was based on earlier studies indicating that deprenyl did not by itself lead to symptomatic improvement in patients with early Parkinson's disease21,22. The small but definite ameliorating influence of deprenyl that we observed on the motor ratings of Parkinson's disease hampers a clear-cut detection of potentially protective actions of this monoamine oxidase inhibitor.
Adverse Effects of Treatment
In keeping with our interim report,6 the adverse effects of tocopherol and deprenyl were infrequent and not serious. The rare occurrence of cardiac arrhythmias among deprenyl-treated subjects is unexplained, but this complication may be related to the monoaminergic effects of the parent compound and its active metabolites3. The infrequent occurrence of deprenyl-related elevations of serum aspartate aminotransferase and alanine aminotransferase levels has been reported previously6,23 and seems to reflect clinically unimportant effects on hepatic or muscle enzymes. Although adverse effects on mental status were rare among our otherwise untreated subjects, deprenyl is known to cause untoward mental changes in patients with Parkinson's disease who are treated concurrently with levodopa or other drugs that enhance dopaminergic activity3.
Therapeutic Recommendations
In contrast to the findings from an uncontrolled pilot study,24 our larger controlled study does not support the use of tocopherol at a dosage of 2000 IU per day in patients who have early Parkinson's disease. The use of deprenyl in a dose of 10 mg per day as monotherapy for early Parkinson's disease delays the development of disability requiring levodopa therapy. Therefore, deprenyl should be considered among the available therapeutic options for the initial treatment of early Parkinson's disease.
Comparison of Present Results with Earlier Results
The effects of deprenyl demonstrated by our present analysis remain strong, but they have been less dramatic over the extended period of observation than the effects we reported previously6. The evidence that deprenyl ameliorates some of the clinical features of Parkinson's disease is clearer in this analysis than in our previous report or in smaller controlled studies carried out by other investigators25,26,27,28. Our ability to detect small clinical effects is related to the large study sample, the extended period of observation, and the longer period of withdrawal from experimental treatments among subjects who had not reached the end point of disability. Previous studies have suggested that deprenyl has a protective effect,6,25,26,28 but this assertion has not yet been established.
Unresolved Issues and Future Investigations
Despite the lack of benefit of tocopherol in this trial, studies of other antioxidant agents in Parkinson's disease are still warranted. Examination of the effects of l-amphetamine metabolites of deprenyl29,30 and of shorter-acting inhibitors of monoamine oxidase type B, such as lazabemide,31 which are not metabolized to active compounds, may help clarify the action of deprenyl. Inhibitors of monoamine oxidase type A, the predominant intraneuronal form of this enzyme,32,33 may also be of interest. The lack of validated biologic markers for the progression of Parkinson's disease hampers attempts to define the action of interventions in the treatment of this disorder.
In the present trial, despite the subjective nature of the primary end point and the large number of investigators, we have consistently found a beneficial effect of deprenyl34. The changes observed in the UPDRS variables supported this finding. The lack of conclusive evidence of a neuroprotective effect of deprenyl justifies further placebo-controlled trials of other promising agents in patients with early Parkinson's disease.
Supported by a Public Health Service grant (NS24778) from the National Institute of Neurological Disorders and Stroke; by grants from the General Clinical Research Centers Program of the National Institutes of Health at Columbia University (RR00645), the University of Virginia (RR00847), the University of Pennsylvania (RR00040), the University of Iowa (RR00059), Ohio State University (RR00034), Massachusetts General Hospital (RR01066), the University of Rochester (RR00044), Brown University (RR02038), Oregon Health Sciences University (RR00334), Baylor College of Medicine (RR00350), the University of California, San Diego (RR00827), Johns Hopkins University (RR00035), the University of Michigan (RR00042), and Washington University (RR00036); the Parkinson's Disease Foundation at Columbia-Presbyterian Medical Center, New York; the National Parkinson Foundation, Miami; the Parkinson Foundation of Canada, Toronto; the United Parkinson Foundation, Chicago; the American Parkinson's Disease Association, New York; and the University of Rochester, Rochester, N.Y.
Source Information
The members of the Parkinson Study Group who conducted the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial and wrote this report are listed in the Appendix. The preparation of the manuscript was overseen by the DATATOP Steering Committee: Ira Shoulson, M.D. (principal investigator), University of Rochester, Rochester, N.Y.; Stanley Fahn, M.D. (co-principal investigator), Columbia-Presbyterian Medical Center, New York; David Oakes, Ph.D. (chief biostatistician), and Karl Kieburtz, M.D. (medical director), University of Rochester; Anthony Lang, M.D., Toronto Hospital, Toronto; J. William Langston, M.D., California Parkinson's Foundation, San Jose; Peter LeWitt, M.D., Sinai Hospital, Detroit; C. Warren Olanow, M.D., University of South Florida, Tampa; John B. Penney, M.D., University of Michigan, Ann Arbor; Caroline Tanner, M.D., Rush-Presbyterian-St. Luke's Medical Center, Chicago; and Alice Rudolph, Ph.D. (senior study coordinator), and Rita M. Pelusio, M.S.Ed. (program manager), University of Rochester.
Address reprint requests to Dr. Ira Shoulson, Box 673, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14642.
References
The following are participants in the DATATOP trial:
Participating Investigators -- W. Koller, University of Kansas, Kansas City; C.W. Olanow, University of South Florida, Tampa; R. Rodnitzky, University of Iowa, Iowa City; J.S. Fink and J.H. Growdon, Massachusetts General Hospital, Boston; G. Paulson, Ohio State University, Columbus; R. Kurlan, University of Rochester, Rochester, N.Y.; J.H. Friedman, Roger Williams General Hospital, Providence, R.I.; S. Gancher and J. Nutt, Oregon Health Sciences University, Portland; A.H. Rajput, University of Saskatchewan, Saskatoon; J.B. Bennett and G.F. Wooten, University of Virginia, Charlottesville; P. LeWitt, Sinai Hospital, Detroit; C. Goetz, C. Tanner, and K. Shannon, Rush-Presbyterian-St. Luke's Medical Center, Chicago; O. Suchowersky, University of Calgary, Calgary, Alta.; M.F. Brin and S.B. Bressman, Columbia-Presbyterian Medical Center, New York; W.J. Weiner and J. Sanchez-Ramos, University of Miami, Miami; J. Jankovic, Baylor College of Medicine, Houston; J.B. Penney, University of Michigan, Ann Arbor; A. Lang, Toronto Hospital, Toronto; M. Hoehn, St. Luke's Hospital, Denver; J. Tetrud, California Parkinson's Foundation, San Jose; J.D. Grimes, Ottawa Civic Hospital, Ottawa; R. Pfeiffer, University of Nebraska, Omaha; C. Shults and L. Thal, University of California, San Diego; S. Gauthier, Montreal General Hospital-McGill University, Montreal; L.I. Golbe, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick; J.S. Perlmutter, Washington University, St. Louis; H. Moses III and S.G. Reich, Johns Hopkins University, Baltimore; and H.I. Hurtig and M. Stern, Graduate Hospital and University of Pennsylvania, Philadelphia.
Site Coordinators -- R. Barter and B. Vetere-Overfield, Kansas City, Kans.; L. Gauger and T. Malapira, Tampa, Fla.; J. Dobson, Iowa City, Iowa; S. Atamian, M. Tennis, J.B. Cohen, G. Desclos, and E. Hoffman, Boston; L. Denio, S. Huber, T. Woike, K. Zoog, R. Mendell, and K. Dudte, Columbus, Ohio; J. Behr, I.F. Gardiner, Rochester, N.Y.; M. Lannon, Providence, R.I.; J. Carter and S. Northrup, Portland, Oreg.; B. Kanigan, Saskatoon, Sask.; M. Turk and E. Landow, Charlottesville, Va.; P. Schlick and K. Mistura, Detroit; V.S. Carroll and J.A. Thelen, Chicago; C. Demong, Calgary, Alta.; L. Winfield and C. Moskowitz, New York; A. Ingenito, C. Sheldon, and L. Cornelius, Miami; D. Heiberg and C. Dunne, Houston; J. Brady, Ann Arbor, Mich.; C. Kierans, L. Belle-Scantlebury, and J. Duff, Toronto; H. Weber, Denver; D. Savoini, P. Lewis, and S.J. Kutner, San Jose, Calif.; P. Gray, Ottawa; C. Glaeske and R. Hofman, Omaha, Neb.; M.M. Pay and D. Salmon, San Diego, Calif.; F. McFaul and D. Amyot, Montreal; M. Bergen, New Brunswick, N.J.; L. McGee-Minnich, St. Louis; P. O'Donnell, Baltimore; and S. Ferrise and K. Shallow, Philadelphia.
Coordination and Data Center -- University of Rochester Medical Center, Rochester, N.Y.: R.M. Pelusio (program manager); A. Rudolph (senior study coordinator); C. Miller (nurse clinician); M. Linsner, J. Connorton, J. Nusbaum, and C. Casaceli (analyst-programmers); C. Irvine, C. Orme, and G.J. Wixsom (information analysts); M. Schirazi, J. Sotack, and H. Randolph (data-control clerks); R. Nobel, D. Baker, D. LaDonna, M.E. Rothfuss, L. Doerr (deceased), L. Rumfola, and B. Kavanaugh (secretarial staff); and J. Wendel (CLINFO manager).
Biostatistics Center -- Department of Biostatistics, University of Rochester Medical Center, Rochester, N.Y.: C. Odoroff (deceased) and D. Oakes (chief biostatisticians); M. McDermott and S. Eberly (biostatisticians); S. Plumb (lead programmer); and A. Watts, L. Yorkey, A. Choi, and K. Gerwitz (analyst-programmers).
Pharmacy Center -- Strong Memorial Hospital, Rochester, N.Y.: P. Evans (chief pharmacist); and L. Dellapena and V. Singletary (pharmacy technicians).
Safety Monitoring Committee -- R. Herndon (chair, January 1, 1987, to June 30, 1988), Portland, Oreg.; P. Tariot (chair, July 1, 1988, to present), Rochester, N.Y.; and E. Bell, R.C. Griggs, and W.J. Hall, Rochester, N.Y.
Scientific Advisory Committee -- C.D. Marsden (chair), London; T.N. Chase, Bethesda, Md.; G. Cohen, J. Fleiss, and R. Mayeux, New York; L. Jacobs and A.J. Moss, Rochester, N.Y.; and E. Melamed, Tel Aviv, Israel.
Assay Standards Committee -- R. Roth (chair), New Haven, Conn.; M. Galloway, Detroit; I. Irwin, San Jose, Calif.; P. LeWitt, Detroit; and G. Vatassery, Minneapolis.
Neuropsychological Testing Committee -- P. Como (chair), Rochester, N.Y.; J. St. Cyr, Toronto; Y. Stern and J. Williams, New York; and R. Wilson, Chicago.
Monitoring Committee, National Institute of Neurological Disorders and Stroke -- E.M. Stadlan (chair), Bethesda, Md.; M. Alter, Philadelphia; K. Bergmann, New Hyde Park, N.Y.; J. Cedarbaum, White Plains, N.Y.; J. Ellenberg, Bethesda, Md.; and R. Kibler, Atlanta.
CSF Assay Center -- Lafayette Clinic, Wayne State University, Detroit: M.P. Galloway (director); M. Kaplan (deceased), R. Lodhi, M.J. Keegan, B. Matthews, and E.A. Novak.
Deprenyl Metabolites Assay Center -- Institute for Medical Research, San Jose, Calif.: I. Irwin (director).
Tocopherol Assay Center -- Our Lady of Mercy Medical Center, Bronx, N.Y.: E. Norkus (director).
Specimen Repository -- Department of Neurology, University of Rochester, Rochester, N.Y.: D. Flood (director), T. McNeill, N. Harary, and L. Koek.
Laboratory Surveillance Testing -- SciCor Laboratories, Indianapolis: R.L. Creveling (director).
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Related Letters:
Protective Effect or Symptomatic Effect of Deprenyl?
Kofman O. S., Shoulson I., The DATATOP Steering Committee on behalf of the Parkinson Study Group
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Full Text
N Engl J Med 1993;
328:1715, Jun 10, 1993.
Correspondence
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