International Journal of Psychiatry in Clinical Practice, 2007; 11(1): 81
LETTER TO THE EDITORS
Dear Editor, This letter refers to the paper by J.K. Rybakowski and M. Jarema (Long-term assessment of the efficacy and tolerability of risperidone in early schizophrenia: An international multicenter study, Int J Psych Clin Pract 2004; 8: 147 152). During the course of monitoring and audit of one of the sites conducting a trial with paliperidone ER in subjects with schizophrenia, serious violations of GCP were found. All ongoing trials were terminated at this site. In addition, a review of previous trials undertaken by this site, including RIS-INT-59, was conducted. Although there was no evidence of violations of GCP in the past at this site, in order to be prudent and cautious, Janssen-Cilag decided to reanalyse the primary efficacy endpoints, after excluding all subjects who participated at this centre. It was also decided that, in order to be transparent, the results of this reanalysis would be conveyed to relevant regulatory authorities and journals. Thus, the primary efficacy endpoints in the RISINT-59 study were reanalysed, this time excluding
all subjects (n 20 out of 205) enrolled at the site in question. Therefore, the study included 185 patients, 100 male (54%), and 85 female (46%), aged 1544 (mean 2697) years. Paranoid schizophrenia was diagnosed in 104 patients (57%) and schizophreniform disorder in 41 patients (22.5%). The results of this reanalysis are shown in Table 1a which should replace Table 1 of that paper. As shown in the table, based on the analysis with and without the site in question, it can be concluded that excluding the data of 20 subjects did not impact the results of the primary efficacy analysis and the conclusions of this study. There was no reanalysis or change of safety findings, as all subjects who participated in the trial were included, as reported in the journal article previously. Janusz K. Rybakowski1 and Marek Jarema2 For the Risperidone-INT-59 Study Group. 1 Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. 2 3rd Department of Psychiatry, Institute of Psychiatry and Neurology, Warsaw, Poland.
Table 1a. The value of PANSS scale before treatment and during last visit results after excluding 20 subjects.
N 185 Total Median value (25%, 75%) Positive symptoms Median value (25%, 75%) Negative symptoms Median value (25%, 75%) General psychopathology Median value (25%, 75%)
PANSS before treatment (baseline)
PANSS Last visit (endpoint)
P value (Wilcoxon test)
PANSS reduction
PANSS percentage reduction
94 (81, 108)
42 (33, 66)
B0.00001
44 (29, 61)
51 (32, 62)
155 (86%)
24 (19, 28)
9 (7, 14)
B0.00001
13 (8, 18)
58 (40, 70)
161 (89%)
24 (18, 30)
12 (8, 18)
B0.00001
10 (5, 16)
47 (24, 59)
141 (78%)
46 (40, 54)
22 (18, 35)
B0.00001
21 (13, 28)
49 (26, 60)
154 (85%)
ISSN 1365-1501 print/ISSN 1471-1788 online # 2007 Taylor & Francis DOI: 10.1080/13651500701267050
N and (%) of pts with reduction 20%
LETTER TO THE EDITORS
Dear Editor, This letter refers to the paper by J.K. Rybakowski and M. Jarema (Long-term assessment of the efficacy and tolerability of risperidone in early schizophrenia: An international multicenter study, Int J Psych Clin Pract 2004; 8: 147 152). During the course of monitoring and audit of one of the sites conducting a trial with paliperidone ER in subjects with schizophrenia, serious violations of GCP were found. All ongoing trials were terminated at this site. In addition, a review of previous trials undertaken by this site, including RIS-INT-59, was conducted. Although there was no evidence of violations of GCP in the past at this site, in order to be prudent and cautious, Janssen-Cilag decided to reanalyse the primary efficacy endpoints, after excluding all subjects who participated at this centre. It was also decided that, in order to be transparent, the results of this reanalysis would be conveyed to relevant regulatory authorities and journals. Thus, the primary efficacy endpoints in the RISINT-59 study were reanalysed, this time excluding
all subjects (n 20 out of 205) enrolled at the site in question. Therefore, the study included 185 patients, 100 male (54%), and 85 female (46%), aged 1544 (mean 2697) years. Paranoid schizophrenia was diagnosed in 104 patients (57%) and schizophreniform disorder in 41 patients (22.5%). The results of this reanalysis are shown in Table 1a which should replace Table 1 of that paper. As shown in the table, based on the analysis with and without the site in question, it can be concluded that excluding the data of 20 subjects did not impact the results of the primary efficacy analysis and the conclusions of this study. There was no reanalysis or change of safety findings, as all subjects who participated in the trial were included, as reported in the journal article previously. Janusz K. Rybakowski1 and Marek Jarema2 For the Risperidone-INT-59 Study Group. 1 Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. 2 3rd Department of Psychiatry, Institute of Psychiatry and Neurology, Warsaw, Poland.
Table 1a. The value of PANSS scale before treatment and during last visit results after excluding 20 subjects.
N 185 Total Median value (25%, 75%) Positive symptoms Median value (25%, 75%) Negative symptoms Median value (25%, 75%) General psychopathology Median value (25%, 75%)
PANSS before treatment (baseline)
PANSS Last visit (endpoint)
P value (Wilcoxon test)
PANSS reduction
PANSS percentage reduction
94 (81, 108)
42 (33, 66)
B0.00001
44 (29, 61)
51 (32, 62)
155 (86%)
24 (19, 28)
9 (7, 14)
B0.00001
13 (8, 18)
58 (40, 70)
161 (89%)
24 (18, 30)
12 (8, 18)
B0.00001
10 (5, 16)
47 (24, 59)
141 (78%)
46 (40, 54)
22 (18, 35)
B0.00001
21 (13, 28)
49 (26, 60)
154 (85%)
ISSN 1365-1501 print/ISSN 1471-1788 online # 2007 Taylor & Francis DOI: 10.1080/13651500701267050
N and (%) of pts with reduction 20%
