- Email: [email protected]
Auditing the quality of clozapine treatment in east Yorkshire
i8. Therapeutics: Treatment Trials
295
ine and ziprasidone, and no significant differences in clinical efficacy were found. Results of this head-to-head comparison should be interpreted with caution due to less than optimal dosing for olanzapine. Conclusions: In comparison to ziprasidone, olanzapine has a larger body of evidence supporting its efficacy, and a greater proportion of the findings for olanzapine have been published, allowing for greater scrutiny of the results. Olanzapine showed some evidence of superior efficacy compared to haloperidol for treatment of overall and negative symptoms of schizophrenia. Unlike olanzapine, it is uncertain whether ziprasidone has statistically comparable or superior efficacy compared to conventional antipsychotics. Firm conclusions regarding the comparison of the efficacy between olanzapine and ziprasidone require additional published clinical trials.
OLANZAPINE VERSUS PLACEBO TREATMENT OF THE SCHIZOPHRENIA PRODROME: ONE YEAR RESULTS T. H. M c G l a s h a n , * R. B. Zipursky, D. O. Perkins, J. A d d i n g t o n , S. W. W o o d s , T. J. Miller, S. Lindborg, E. M a r q u e z , K. H a w k i n s , R. E. H o f f m a n , M. Tohen, A. Breier
Psychiatry, Yale University, New Haven, CT, USA This is the first multi-site randomized, double-blind, placebo controlled trial to test the safety and efficacy of Olanzapine for the preonset phase of the prodrome to schizophrenia. Consenting patients meeting prodromal symptom and syndrome criteria receive drug or placebo at fixed-flexible doses for one year and no pills for a second year. Aims are to test whether drug delays or prevents psychosis onset (conversion), reduces prodromal symptoms, and produces minimal side effects. The last patient finished the first year, and one year results were unblinded. At baseline 60 treatment seeking patients met prodromal criteria by the Structured Interview for Prodromal Syndromes (mean age 17.7 years, 65% male, 67% Caucasian) and were randomly assigned to Olanzapine 5-15 mg or placebo po once daily. Efficacy for Conversion: Fifteen patients developed psychosis according to the study's Presence of Psychosis Scale, an overall rate of 25%. Of these, 10 patients were placebo and 5 were drug (ns). The majority (8 of 15) converted within the first month from baseline. This included all Olanzapine converters who, compared to the placebo converters, received lower prescribed study drug (7.7 mg vs. 10.5 mg, ns) and were less compliant in number of days taking drug (79% vs. 93%, ns). Safety: A mean change analysis found no differences between drug and placebo on vital signs (LOCF) or EPS (OC). Weight gain (in kg) from baseline to endpoint was higher for drug (8.0 vs. 0.3, p<.012). Symptoms: Severity of prodromal symptoms (Scale of Prodromal Symptoms), psychotic symptoms (PANSS), depression (MADRS), and mania (YMRS) were compared at 12 weeks, 6 months, and 1 year using mixed regressions. PANSS, MADRS, and YMRS symptom levels were minimal at baseline and changed little with time. Positive and total prodromal symptoms were reduced in severity from baseline in the Olanzapine arm for all three time points. Significance: At one year Olanzapine appears effective in treating prodromal symptoms and is associated with weight gain but not EPS. It reduces conversion to psychosis by 50%, a difference suggestive but not significant. Two year data are still blinded. Implications for future prodromal intervention studies include improving true positive prodromal identification, larger samples, and a higher initial dose of Olanzapine. Future research is needed before treatment recommendations can bemade.
ARIPIPRAZOLE FOR LONG-TERM MAINTENANCE TREATMENT OF SCHIZOPHRENIA R. D. M c Q u a d e , * M. Kujawa, A. R. Saha, G. G. Ingenito, M. W. Ali, X. Luo, D. G. Archibald, W. H. C a r s o n
Bristol-Myers Squibb, Lawrenceville, N J, USA The purpose of this study was to evaluate the maintenance of effect and long-term efficacy, safety, and tolerability of aripiprazole, a dopamine-serotonin system stabilizer, compared to haloperidol when administered for 52 weeks. A multicenter, double-blind study was conducted in 1,294 patients with acute relapse of chronic schizophrenia randomized to aripiprazole 30 mg/d (n=861) or haloperidol 10 mg/d (n=433). A one-time dose reduction was allowed to aripiprazole 20 mg/d and haloperidol 7 mg/d. Efficacy evaluations included PANSS and MADRS scores. A significantly greater proportion of patients treated with aripiprazole demonstrated response and remained on treatment at weeks 8, 26, and 52 compared to haloperidol (Week 52: 40% vs 27%, p<0.001). Aripiprazole produced statistically significant improvements in the PANSS Negative Subscale Score at weeks 26 and 52 (both p<0.03). Aripiprazole also demonstrated significant improvement from baseline in depressive symptoms as shown in the MADRS at weeks 8, 26, and 52, compared to haloperidol (all p<0.03). The discontinuation rate due to an adverse event was significantly lower in the aripiprazole group than in the haloperidol group (p<0.001). The overall incidence of EPS-related adverse events was significantly lower with aripiprazole than with haloperidol (p< 0.001). Both treatments resulted in comparable weight gain. There was no significant difference in QTc interval between both groups. Aripiprazole may represent the next-generation antipsychotic leading to increased adherence to treatment in schizophrenia due to significantly greater improvements in negative and depressive symptoms, and a superior safety and tolerability profile compared to haloperidol.
AUDITING THE QUALITY OF CLOZAPINE TREATMENT IN EAST YORKSHIRE A. M. Mortimer,* K. Carr, R Fee
Psychiatry, University of Hull, Hull, East Yorkshire, United Kingdom Effective use of clozapine was examined in a casenote audit of all patients (n = 63, 52 males and 13 females) in East Yorkshire (population 0.5 million). Most patients (49) had been on clozapine for over a year. Only half (33) had been supplied with information on clozapine, or had an opportunity to discuss treatment prior to commencement. Less than a third of patients (12-17) were monitored appropriately during the first 6 hours of therapy, and less than a third (19) of the patients' haematology records were stored properly. Most patients on doses associated with epilepsy i.e. 600mg daily or more, were not on anticonvulsants (7/10). Almost half (28/63) were comedicated with other psychotropic drugs, mostly antidepressants (19) and bendodiazepines (9). Most of these patients (21/28) were on a single extra psychotropic, 6 were on 2 extra psychotropics and 1 was on 3.8 patients were comedicated for no apparent reason with 3 on antidepressants, 3 on benzodiazepines, 2 on lithium, 1 on haloperidol, 1 on a beta blocker and 1 on sodium valproate. 6 patients were on 1 redundant medication, 1 on 2 and 1 on 3. Use of serum levels
International Congress on Schizophrenia Research 2003
296 to optimize treatment was poor, with 10/20 non-responding patients, 14/22 patients suffering side effects and 8/15 possibly non-compliant patients having their levels checked. However, most patients had a serum level on achieving their maintenance dose (36/44) and at 612 monthly intervals thereafter (33/41). All patients had reviews of their mental state on clozapine, mad nearly all (61/63) had side effects enquired about, but in a third (13/40) documented side effect concerns were not acted upon. Similarly nearly a third of concerns regarding unresolved mental state difficulties were not acted upon (29/93). However nearly all (57) patients were believed to be benefitting from ctozapine: of the remaining 6, 2 had not yet reached their final dosage. Despite significant room for improvement in the management of patients on clozapine, almost all (93%) were felt to be doing well on this drug. It is likely that a minority of eligible patients are currently receiving clozapine treatment: if concordance with the UK government's NICE guidance is to be achieved, there needs to be a considerable investment in resources to ensure that the benefits of clozapine treatment are maximized.
COST-EFFECTIVENESS OF OLANZAPINE COMPARED TO RISPERIDONE AND HALOPERIDOL IN THE TREATMENT OF PATIENTS WITH SCHIZOPHRENIA: RESULTS FROM A U.S. RANDOMIZED CONTROLLED TRIAL M. Namjoshi,* C. A. Young, L. H u a n g , E. Edgell, A. Breier
Lilly Resealvh Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Introduction: An objective of this study was to determine the costeffectiveness of olanzapine compared to risperidone and haloperidol in the treatment of patients with schizophrenia. Methods: Patients (n=364) with schizophrenia were randomized to treatment with olanzapine (5-20 rag/day), risperidone (2-10 mg/day), or haloperidol (2-19 rag/day) for 52 weeks. Clinical outcomes were assessed using the PANSS total score. Inpatient and outpatient resource use was assessed using a module developed for the study. Inpatient resource use included the number of hospital admissions and the length of hospital stay per admission. Outpatient resource use included visits to health care professionals, emergency room visits, partial care, and home health care. Local costs were assigned to the resources used, missing data were imputed, and medians were calculated as the measure of central tendency. Results: Of the patients with baseline and endpoint assessments, 137 patients were randomized to olanzapine, 126 to risperidone, and 82 to haloperidol. The median doses for the three cohorts were 13. l mg for olanzapine, 5.7mg for risperidone, and 8.2mg for haloperidol. There were no significant differences at baseline between the three treatment groups on the PANSS total score. Patients on olanzapine demonstrated a greater change on the PANSS total score compared to both risperidone (-ll.5 vs. -9.18, p=0.24) and haloperidol (-11.5 vs. -7.0, p=0.01) over 52 weeks of treatment. Median total health services costs for olanzapine patients were $1,014.50, while those for risperidone and haloperidol patients were $1,667.44 and $1,066.50 respectively. Conclusion: The results of this study indicate that olanzapine treatment is associated with better clinical outcomes that result in lower resource utilization and health services costs compared to risperidone and haloperidol, and is therefore a cost-effective treatment option for patients with schizophrenia.
18. Therapeutics: Treatment Trials EARLY INTERVENTION UTILISING GROUP PSYCHOLOGICAL THERAPY FOR AUDITORY HALLUCINATIONS : A PRELIMINARY EFFICACY TRIAL E. K. N e w t o n , * T. W y k e s , S. L a n d a u , R Smith, E M o n k s , S. Shergill, R. M e l h u i s h , M. Larkin
Department of Clinical Psychology, University College London, London, United Kingdom For a significant proportion of people who develop schizophrenia, onset occurs during adolescence. This group tends to suffer from a more chronic course of illness with less favourable outcomes than those whose onset occurs during adulthood. The experience of auditory hallucinations is the most common and distressing symptom experienced by people suffering from schizophrenia. It has been suggested that auditory hallucinations may be most frightening and difficult to cope with shortly after their onset. However, this may also be the period in which auditory hallucinations will be most responsive to psychological treatment. Recent efficacy studies of group psychological therapy for voices have found significant reductions in symptoms and distress, and increases in coping (Wykes et al., 1999). This study investigates the efficacy of group psychological therapy for young people (14 to 2l years, N=22) suffering from distressing auditory hallucinations and explores their experiences of receiving treatment. It uses a mixed-method approach. Changes in symptoms over a six-week waiting period, treatment and follow-up period were investigated using structured interview schedules and self-rating questionnaires. In addition, a sub-set of participants were interviewed using a semi-structured interview schedule to collect detailed verbal accounts of their experiences of the therapy. Significant reductions in the main outcome measure (PSYRATS auditory hallucinations rating scale) were found following treatment as well as significant changes on ancillary measures (e.g. coping and activity level). The qualitative data supported the quantitative findings; the benefits of the treatment group were clearly articulated by those who attended. These findings are consistent with the literature that suggest that psychological therapies should be an integral part of treatment for young people with psychosis.
MESIFOS: MEDICATION STRATEGIES IN FIRST ONSET SCHIZOPHRENIA EFFECTS OF SHORT VERSUS SUSTAINED ANTIPSYCHOTIC TREATMENT ON QUALITY OF LIFE AFTER FIRST EPISODE PSYCHOSIS: A RANDOMIZED TRIAL E N i e n h u i s , * A. W u n d e r i n k , D. W i e r s m a , R. J. v a n den B o s c h , R. B r u g g e m a n , G. Faber, J. van der Linde, E. Noorthoorn, C. J. Slooff, E V l a m i n c k , D. van der Werf, E de Wit
Dept of Psychiatry, University of Groningen, Groningen, Netherlands Treatment guidelines for first episode psychosis currently imply continuing antipsychotic treatment for at least one or two years after remission, depending on local consensus rules. Many patients however do not easily comply with sustained treatment. Subjective side effects of antipsychotic treatment recently gained interest as a major cause of nonadherence to treatment, in spite of better results of sustained treatment regarding the prevention of positive symptoms and
International Congress on Schizophrenia Research 2003
295
ine and ziprasidone, and no significant differences in clinical efficacy were found. Results of this head-to-head comparison should be interpreted with caution due to less than optimal dosing for olanzapine. Conclusions: In comparison to ziprasidone, olanzapine has a larger body of evidence supporting its efficacy, and a greater proportion of the findings for olanzapine have been published, allowing for greater scrutiny of the results. Olanzapine showed some evidence of superior efficacy compared to haloperidol for treatment of overall and negative symptoms of schizophrenia. Unlike olanzapine, it is uncertain whether ziprasidone has statistically comparable or superior efficacy compared to conventional antipsychotics. Firm conclusions regarding the comparison of the efficacy between olanzapine and ziprasidone require additional published clinical trials.
OLANZAPINE VERSUS PLACEBO TREATMENT OF THE SCHIZOPHRENIA PRODROME: ONE YEAR RESULTS T. H. M c G l a s h a n , * R. B. Zipursky, D. O. Perkins, J. A d d i n g t o n , S. W. W o o d s , T. J. Miller, S. Lindborg, E. M a r q u e z , K. H a w k i n s , R. E. H o f f m a n , M. Tohen, A. Breier
Psychiatry, Yale University, New Haven, CT, USA This is the first multi-site randomized, double-blind, placebo controlled trial to test the safety and efficacy of Olanzapine for the preonset phase of the prodrome to schizophrenia. Consenting patients meeting prodromal symptom and syndrome criteria receive drug or placebo at fixed-flexible doses for one year and no pills for a second year. Aims are to test whether drug delays or prevents psychosis onset (conversion), reduces prodromal symptoms, and produces minimal side effects. The last patient finished the first year, and one year results were unblinded. At baseline 60 treatment seeking patients met prodromal criteria by the Structured Interview for Prodromal Syndromes (mean age 17.7 years, 65% male, 67% Caucasian) and were randomly assigned to Olanzapine 5-15 mg or placebo po once daily. Efficacy for Conversion: Fifteen patients developed psychosis according to the study's Presence of Psychosis Scale, an overall rate of 25%. Of these, 10 patients were placebo and 5 were drug (ns). The majority (8 of 15) converted within the first month from baseline. This included all Olanzapine converters who, compared to the placebo converters, received lower prescribed study drug (7.7 mg vs. 10.5 mg, ns) and were less compliant in number of days taking drug (79% vs. 93%, ns). Safety: A mean change analysis found no differences between drug and placebo on vital signs (LOCF) or EPS (OC). Weight gain (in kg) from baseline to endpoint was higher for drug (8.0 vs. 0.3, p<.012). Symptoms: Severity of prodromal symptoms (Scale of Prodromal Symptoms), psychotic symptoms (PANSS), depression (MADRS), and mania (YMRS) were compared at 12 weeks, 6 months, and 1 year using mixed regressions. PANSS, MADRS, and YMRS symptom levels were minimal at baseline and changed little with time. Positive and total prodromal symptoms were reduced in severity from baseline in the Olanzapine arm for all three time points. Significance: At one year Olanzapine appears effective in treating prodromal symptoms and is associated with weight gain but not EPS. It reduces conversion to psychosis by 50%, a difference suggestive but not significant. Two year data are still blinded. Implications for future prodromal intervention studies include improving true positive prodromal identification, larger samples, and a higher initial dose of Olanzapine. Future research is needed before treatment recommendations can bemade.
ARIPIPRAZOLE FOR LONG-TERM MAINTENANCE TREATMENT OF SCHIZOPHRENIA R. D. M c Q u a d e , * M. Kujawa, A. R. Saha, G. G. Ingenito, M. W. Ali, X. Luo, D. G. Archibald, W. H. C a r s o n
Bristol-Myers Squibb, Lawrenceville, N J, USA The purpose of this study was to evaluate the maintenance of effect and long-term efficacy, safety, and tolerability of aripiprazole, a dopamine-serotonin system stabilizer, compared to haloperidol when administered for 52 weeks. A multicenter, double-blind study was conducted in 1,294 patients with acute relapse of chronic schizophrenia randomized to aripiprazole 30 mg/d (n=861) or haloperidol 10 mg/d (n=433). A one-time dose reduction was allowed to aripiprazole 20 mg/d and haloperidol 7 mg/d. Efficacy evaluations included PANSS and MADRS scores. A significantly greater proportion of patients treated with aripiprazole demonstrated response and remained on treatment at weeks 8, 26, and 52 compared to haloperidol (Week 52: 40% vs 27%, p<0.001). Aripiprazole produced statistically significant improvements in the PANSS Negative Subscale Score at weeks 26 and 52 (both p<0.03). Aripiprazole also demonstrated significant improvement from baseline in depressive symptoms as shown in the MADRS at weeks 8, 26, and 52, compared to haloperidol (all p<0.03). The discontinuation rate due to an adverse event was significantly lower in the aripiprazole group than in the haloperidol group (p<0.001). The overall incidence of EPS-related adverse events was significantly lower with aripiprazole than with haloperidol (p< 0.001). Both treatments resulted in comparable weight gain. There was no significant difference in QTc interval between both groups. Aripiprazole may represent the next-generation antipsychotic leading to increased adherence to treatment in schizophrenia due to significantly greater improvements in negative and depressive symptoms, and a superior safety and tolerability profile compared to haloperidol.
AUDITING THE QUALITY OF CLOZAPINE TREATMENT IN EAST YORKSHIRE A. M. Mortimer,* K. Carr, R Fee
Psychiatry, University of Hull, Hull, East Yorkshire, United Kingdom Effective use of clozapine was examined in a casenote audit of all patients (n = 63, 52 males and 13 females) in East Yorkshire (population 0.5 million). Most patients (49) had been on clozapine for over a year. Only half (33) had been supplied with information on clozapine, or had an opportunity to discuss treatment prior to commencement. Less than a third of patients (12-17) were monitored appropriately during the first 6 hours of therapy, and less than a third (19) of the patients' haematology records were stored properly. Most patients on doses associated with epilepsy i.e. 600mg daily or more, were not on anticonvulsants (7/10). Almost half (28/63) were comedicated with other psychotropic drugs, mostly antidepressants (19) and bendodiazepines (9). Most of these patients (21/28) were on a single extra psychotropic, 6 were on 2 extra psychotropics and 1 was on 3.8 patients were comedicated for no apparent reason with 3 on antidepressants, 3 on benzodiazepines, 2 on lithium, 1 on haloperidol, 1 on a beta blocker and 1 on sodium valproate. 6 patients were on 1 redundant medication, 1 on 2 and 1 on 3. Use of serum levels
International Congress on Schizophrenia Research 2003
296 to optimize treatment was poor, with 10/20 non-responding patients, 14/22 patients suffering side effects and 8/15 possibly non-compliant patients having their levels checked. However, most patients had a serum level on achieving their maintenance dose (36/44) and at 612 monthly intervals thereafter (33/41). All patients had reviews of their mental state on clozapine, mad nearly all (61/63) had side effects enquired about, but in a third (13/40) documented side effect concerns were not acted upon. Similarly nearly a third of concerns regarding unresolved mental state difficulties were not acted upon (29/93). However nearly all (57) patients were believed to be benefitting from ctozapine: of the remaining 6, 2 had not yet reached their final dosage. Despite significant room for improvement in the management of patients on clozapine, almost all (93%) were felt to be doing well on this drug. It is likely that a minority of eligible patients are currently receiving clozapine treatment: if concordance with the UK government's NICE guidance is to be achieved, there needs to be a considerable investment in resources to ensure that the benefits of clozapine treatment are maximized.
COST-EFFECTIVENESS OF OLANZAPINE COMPARED TO RISPERIDONE AND HALOPERIDOL IN THE TREATMENT OF PATIENTS WITH SCHIZOPHRENIA: RESULTS FROM A U.S. RANDOMIZED CONTROLLED TRIAL M. Namjoshi,* C. A. Young, L. H u a n g , E. Edgell, A. Breier
Lilly Resealvh Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Introduction: An objective of this study was to determine the costeffectiveness of olanzapine compared to risperidone and haloperidol in the treatment of patients with schizophrenia. Methods: Patients (n=364) with schizophrenia were randomized to treatment with olanzapine (5-20 rag/day), risperidone (2-10 mg/day), or haloperidol (2-19 rag/day) for 52 weeks. Clinical outcomes were assessed using the PANSS total score. Inpatient and outpatient resource use was assessed using a module developed for the study. Inpatient resource use included the number of hospital admissions and the length of hospital stay per admission. Outpatient resource use included visits to health care professionals, emergency room visits, partial care, and home health care. Local costs were assigned to the resources used, missing data were imputed, and medians were calculated as the measure of central tendency. Results: Of the patients with baseline and endpoint assessments, 137 patients were randomized to olanzapine, 126 to risperidone, and 82 to haloperidol. The median doses for the three cohorts were 13. l mg for olanzapine, 5.7mg for risperidone, and 8.2mg for haloperidol. There were no significant differences at baseline between the three treatment groups on the PANSS total score. Patients on olanzapine demonstrated a greater change on the PANSS total score compared to both risperidone (-ll.5 vs. -9.18, p=0.24) and haloperidol (-11.5 vs. -7.0, p=0.01) over 52 weeks of treatment. Median total health services costs for olanzapine patients were $1,014.50, while those for risperidone and haloperidol patients were $1,667.44 and $1,066.50 respectively. Conclusion: The results of this study indicate that olanzapine treatment is associated with better clinical outcomes that result in lower resource utilization and health services costs compared to risperidone and haloperidol, and is therefore a cost-effective treatment option for patients with schizophrenia.
18. Therapeutics: Treatment Trials EARLY INTERVENTION UTILISING GROUP PSYCHOLOGICAL THERAPY FOR AUDITORY HALLUCINATIONS : A PRELIMINARY EFFICACY TRIAL E. K. N e w t o n , * T. W y k e s , S. L a n d a u , R Smith, E M o n k s , S. Shergill, R. M e l h u i s h , M. Larkin
Department of Clinical Psychology, University College London, London, United Kingdom For a significant proportion of people who develop schizophrenia, onset occurs during adolescence. This group tends to suffer from a more chronic course of illness with less favourable outcomes than those whose onset occurs during adulthood. The experience of auditory hallucinations is the most common and distressing symptom experienced by people suffering from schizophrenia. It has been suggested that auditory hallucinations may be most frightening and difficult to cope with shortly after their onset. However, this may also be the period in which auditory hallucinations will be most responsive to psychological treatment. Recent efficacy studies of group psychological therapy for voices have found significant reductions in symptoms and distress, and increases in coping (Wykes et al., 1999). This study investigates the efficacy of group psychological therapy for young people (14 to 2l years, N=22) suffering from distressing auditory hallucinations and explores their experiences of receiving treatment. It uses a mixed-method approach. Changes in symptoms over a six-week waiting period, treatment and follow-up period were investigated using structured interview schedules and self-rating questionnaires. In addition, a sub-set of participants were interviewed using a semi-structured interview schedule to collect detailed verbal accounts of their experiences of the therapy. Significant reductions in the main outcome measure (PSYRATS auditory hallucinations rating scale) were found following treatment as well as significant changes on ancillary measures (e.g. coping and activity level). The qualitative data supported the quantitative findings; the benefits of the treatment group were clearly articulated by those who attended. These findings are consistent with the literature that suggest that psychological therapies should be an integral part of treatment for young people with psychosis.
MESIFOS: MEDICATION STRATEGIES IN FIRST ONSET SCHIZOPHRENIA EFFECTS OF SHORT VERSUS SUSTAINED ANTIPSYCHOTIC TREATMENT ON QUALITY OF LIFE AFTER FIRST EPISODE PSYCHOSIS: A RANDOMIZED TRIAL E N i e n h u i s , * A. W u n d e r i n k , D. W i e r s m a , R. J. v a n den B o s c h , R. B r u g g e m a n , G. Faber, J. van der Linde, E. Noorthoorn, C. J. Slooff, E V l a m i n c k , D. van der Werf, E de Wit
Dept of Psychiatry, University of Groningen, Groningen, Netherlands Treatment guidelines for first episode psychosis currently imply continuing antipsychotic treatment for at least one or two years after remission, depending on local consensus rules. Many patients however do not easily comply with sustained treatment. Subjective side effects of antipsychotic treatment recently gained interest as a major cause of nonadherence to treatment, in spite of better results of sustained treatment regarding the prevention of positive symptoms and
International Congress on Schizophrenia Research 2003