Ginkgo biloba for mild to moderate dementia in a community setting: a pragmatic, randomised, parallel-group, double-blind, placebo-controlled trial
|
|
- Ira George
- 6 years ago
- Views:
Transcription
1 INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Int J Geriatr Psychiatry 2008; 23: Published online 9 June 2008 in Wiley InterScience ( Ginkgo biloba for mild to moderate dementia in a community setting: a pragmatic, randomised, parallel-group, double-blind, placebo-controlled trial Rob McCarney 1 *, Peter Fisher 2, Steve Iliffe 3, Robbert van Haselen 4, Mark Griffin 3, Jan van der Meulen 5 and James Warner 1 1 Department of Psychological Medicine, Imperial College London, UK 2 Royal London Homœopathic Hospital, UK 3 Department of Primary Care and Population Sciences, UCL, UK 4 International Institute for Integrated Medicine, France 5 London School of Hygiene and Tropical Medicine, UK SUMMARY Objectives Doubt over the cost-effectiveness of the cholinesterase inhibitors in dementia has renewed interest in alternative treatments such as Ginkgo biloba. We aimed to determine the effectiveness and the safety profile of Ginkgo biloba for treating early stage dementia in a community setting. Methods We conducted a community-based, pragmatic, randomised, double-blind, parallel-group trial where participants were given a standardised extract of Ginkgo biloba (120 mg daily) or a placebo control for 6 months. Our primary outcomes were cognitive functioning (ADAS-Cog) and participant and carer-rated quality of life (QOL-AD). Results We recruited 176 participants, mainly through general practices. In the ANCOVA model with baseline score as a co-variate (n ¼ 176), Ginkgo did not have a significant effect on outcome at six months on either the ADAS-Cog score (p ¼ 0.392), the participant-rated QOL-AD score ( p ¼ 0.787) nor the carer-rated QOL-AD score ( p ¼ 0.222). Conclusion We found no evidence that a standard dose of high purity Ginkgo biloba confers benefit in mild-moderate dementia over 6 months. Copyright # 2008 John Wiley & Sons, Ltd. key words Ginkgo biloba; Alzheimer disease; vascular dementia; randomised controlled trials BACKGROUND Current prescribing guidelines from the National Institute for Health and Clinical Excellence (2006) severely restrict the use of cholinesterase inhibitors (AChls). Safe, inexpensive and effective alternatives are needed for treating dementia and there is much interest in the use of the herbal medicine Ginkgo (McCarney and Warner, 2007). The benefit of Ginkgo however remains unclear. A recent Cochrane review (Birks et al., 2002), concluded that while a small effect is suggested the evidence is inconsistent. The null *Correspondence to: Dr R. McCarney, St Charles Hospital, Exmoor Street, London, W10 6DZ, UK. robmccarney@googl .com Copyright # 2008 John Wiley & Sons, Ltd. hypothesis was that compared to placebo, Ginkgo biloba taken for 6 months by community-dwelling individuals with mild to moderate dementia has no effect on cognitive functioning and the participant s quality of life. METHODS We conducted a community-based, pragmatic, randomised, double-blind, parallel-group trial where participants were given a standardised extract of Ginkgo biloba (120 mg daily) or a placebo control for 6 months. We were interested in the effect of Ginkgo vs placebo, which is reported here, but also attempted to quantify the Hawthorne effect (effect of trial Received 21 November 2007 Accepted 10 April 2008
2 an rct of ginkgo for dementia 1223 participation on treatment response) which is reported elsewhere (McCarney et al., 2007). The trial was approved by South West Multi-Centre Research Ethics Committee (ref: MREC/02/6/35) and was registered with Current Controlled Trials (ISRCTN ). The trial was designed and executed in collaboration with consumer representatives from the Alzheimer s society (UK) and monitored by an international advisory board (IAB), independent of the trial steering committee. Participants We recruited participants in Greater London (UK) and adjoining regions through referrals from general practices, old age psychiatrists and other health care professionals; and from direct responses to advertising in Alzheimer Society newsletters, London-based newspapers, and posters in Age Concern centres. As this was a pragmatic study, we recruited people with a clinical diagnosis of dementia made by the referring clinician rather than diagnostic criteria such as the National Institute of Neurological and Communicative Diseases and Stroke/ Alzheimer s Disease and Related Disorders Association (NINCDS-ADRDA) (McKhann et al., 1984), which are unlikely to be used widely in clinical settings. Inclusion criteria were: aged 55 years or over; presence of a carer; informed consent or if lacking capacity, their assent and the agreement of their nominated carer; sufficient command of English; clinical diagnosis of dementia (subsequently sub-classified using DSM-IV criteria) (American Psychiatric Association, 2000); a Mini Mental State Examination (MMSE) (Folstein et al., 1975) score of inclusive; living in the community. Exclusion criteria were: use of Ginkgo in 2 weeks prior to the baseline assessment; commencement of cholinesterase inhibiting drugs within 2 months of baseline or during follow-up; concomitant warfarin therapy; known bleeding abnormalities [a link has been suggested between life-threatening risk of haemorrhage (Vale, 1998; Kayne, 2001) and the ingestion of Ginkgo; therefore we considered a history of abnormal clotting or the use of anti-coagulation therapy grounds for exclusion]. Interventions Participants were randomised to receive either active treatment or placebo for 6 months. Active treatment was a standardised, concentrated Ginkgo biloba extract (EGb ) containing 24% Ginkgo-flavone glycosides and 6% terpene lactones; which are thought to be the active principles in the extract. To facilitate blinding, the lactose-based placebo were identically packaged and labelled, physically indistinguishable tablets containing traces of quinine hydrochloride to mimic the bitter taste of Ginkgo. A placebo such as this had been used before (van Dongen et al., 2000). The trial medication was manufactured in accordance with European Union Standards and purchased from Schwabe Pharma (Willmar-Schwabe-Str. 4, Karlsruhe, Germany), who certified its purity. Both treatments were supplied in blister packs marked with the days of the week. Participants were requested to take one 60 mg tablet twice a day for a total daily dose of 120 mg over the 6 months of follow-up. Follow-up In order to assess the Hawthorne effect, participants were randomised to standard follow-up (with visits at baseline and 2, 4 and 6 months post randomisation) or minimal follow-up (with an abbreviated assessment at baseline and a full assessment at 6 months). We conducted the assessments in the participant s or their carer s home (see Table 1). Outcomes The primary outcome measures were: (i) cognitive functioning, as measured by the ADAS-Cog (Rosen et al., 1984), a 0 70 point scale with a higher score indicating worse cognition; and (ii) quality of life, rated by the participant and their nominated carer, as measured by the QOL-AD (Logsdon et al., 1999). Both 13-item scales, scoring between points with a higher score indicating better quality of life. Secondary outcome measures were: (i) psychopathology and the resulting distress to the carer, as measured by the Neuro-Psychiatric Inventory with caregiver Distress scale (NPI-D) (Cummings et al., 1994), a 12-item scale scoring for psychopathology and 0 60 for caregiver distress; (ii) caregiver-reported daily living and social behaviour score, as measured by the Geriatric Evaluation by Relative s Rating Instrument (GERRI) (Schwartz, 1983), a 49-item scale scored 1 5 for each item and averaged for the overall score, a higher score indicating greater impairment; (iii) caregiver-reported burden of caring as measures by the 12-item Zarit Burden Interview (ZBI) (Bedard et al., 2001), scoring 0 48 with a higher score indicating greater burden; (iv) a report of caregiver health, as measured by the visual analogue scale of the European Quality of Life Visual Analogue Scale (EQ-VAS) (The EuroQol
3 1224 r. mccarney ET AL. Table 1. Administration of outcome measures Time point in study Intensive follow-up group Minimal follow-up group Questionnaire Subject* Questionnaire Subject* Baseline 0 ADAS-Cog, QOL-AD, Participant ADAS-Cog, QOL-AD Participant NPI-D, GERRI EQ-5D, ZBI Carer EQ-5D, ZBI Carer 2 months ADAS-Cog, QOL-AD, Participant NPI-D EQ-5D, ZBI Carer 4 months ADAS-Cog, QOL-AD, Participant NPI-D EQ-5D, ZBI Carer End of study 6 months ADAS-Cog, QOL-AD, Participant ADAS-Cog, QOL-AD, Participant NPI-D, GERRI NPI-D, GERRI EQ-5D, ZBI Carer EQ-5D, ZBI Carer *Subject denotes person assessed by measure. Some assessments are completed by the carer but reporting on the participant (e.g. GERRI and NPI-D). For measures such as this the participant is the subject. Group, 1990), scoring with higher score indicating better health; (v) a caregiver-reported global measure of benefit, by asking at the final follow-up, If you could continue the medication the person you care for has been receiving in this trial, would you (do you feel that it has helped him/her)? (Answer: yes or no); (vi) blood coagulation times as measures by Activated Clotting Time (ACT) using near-patient testing with the Coaguchek Pro DM 1 (Roche Diagnostics, Germany). All outcome measures, except the global measure, are previously validated tools (and in most cases commonly) used in dementia trials. All outcomes were administered by a trained researcher during a home visit. The ADAS-Cog was scored by the researcher; all other measures were scored by the participant or their carer. The field researchers were given full training in the use of the instruments and regular reviews were held amongst the researchers to ensure consistency in scoring the ADAS-Cog. In keeping with the pragmatic nature of the study, other interventions were allowed during the trial, but commencement of an AChI was grounds for withdrawal. Therefore some contamination of the interventions (through factors such as education, support from local voluntary organisations and undeclared use of Ginkgo or AChIs) was possible. To evaluate the impact of this, at each follow-up visit information about non-trial Ginkgo use and visits to secondary care services was sought. All changes in conventional treatments were recorded at the 6-month assessment. Sample size We calculated sample size for an analysable sample of 200 participants based on 80% power and a between-group difference of four points (on a 70-point scale) on the ADAS-Cog, which is the lower limit of what we would regard as clinically significant, with a SD of 11 points (Raskind et al., 2000) using a two-tailed significance level of 5%. Randomisation procedure and blinding A22factorial design with two separate randomisations, resulting in participants being randomised to one of four arms, was employed. Both factors consisted of two levels: medication group (Ginkgo and placebo); and level of follow-up (minimal or standard). This produced four groups: the Ginkgo group with standard follow-up, the Ginkgo group with minimal follow-up, the placebo group with standard follow-up and the placebo group with minimal follow-up. The randomisation codes were generated using the computer algorithm RCODE v.4.8 (Schwabe, 2002). Study medication was randomised in blocks of two and blocks were allocated to a general practice when a participant was recruited from that practice. Participants were allocated a code on entry into the trial by the researcher. Researchers undertaking the analysis and the trial statistician remained blind until completion of the analysis defined in the analysis protocol. Participants, their carers and clinicians responsible for the participant (GPs and consultants) remained
4 an rct of ginkgo for dementia 1225 blinded to the allocation during their participation. Participants were de-blinded in the event of a serious adverse event or once all participants in that block completed or withdrew from the study. The deblindings were administered by members of the study team not directly involved in the evaluation and were concealed from assessors and statistician. Success of blinding was tested by asking the researcher undertaking assessments and the carer to indicate whether they believed the participant had been taking Ginkgo or placebo. Statistical methods The analyses reported here were all planned a priori and documented in an analysis protocol. The primary analysis was intention to treat (ITT), with individuals analysed in their randomisation group, irrespective of whether they completed the trial. In order to adjust for baseline scores, when comparing the outcomes between the treatment groups, analysis of co-variance (ANCOVA) was used. Normal distributions were assumed for the ANCOVA analyses and were checked using residuals from the regression models. If data showed substantial deviations from these assumptions, appropriate transformations were used. Adjusted differences in means (b) are presented so that a positive b value favours Ginkgo and negative value favours placebo; with 95% Confidence Intervals (CI) and p-values. Where these assumptions were not met distribution-free statistical tests were employed. Interaction between treatment group and follow-up group was assessed. To take account of missing data in the ITT analysis, missing baseline data were imputed using hot decking, where values were selected at random from donors amongst the non-missing data set that had similar values for the filter variables. The filter variable for ADAS-Cog score was the MMSE score and for all other variables were age, sex and randomisation group. For the 6-month data, multiple imputation techniques were used with five imputations using a predictive model based approach with ordinary least-squares regression; from a distribution using baseline score, follow-up group and treatment group. Standard analysis (ANCOVA) was used for each of the resulting data sets generated by the imputation process then combined using standard explicit formulae (Rubin and Schenker, 1991). All imputed data were assumed missing at random. Adverse events were initially evaluated by clinicians in the study team (PF and JW) and were described and recorded by treatment group in line with ICH Good Clinical Practice guidelines (ICH, 1997). Serious events were referred to the IAB. The causal relationship to the trial medication, MedDRA disease classification and category of AE were also recorded. Two further analyses were undertaken: an analysis using all evaluable (i.e. non-imputed) data available at 6 months only and a per-protocol analysis. The perprotocol analysis investigated the effect of adherence to the treatment on the primary outcome variables. To be included in this analysis, participants needed to have: completed the study; had relevant data collected (with no imputation for missing data); been followed-up at all time points (according to his or her allocation to minimal or standard follow-up); and taken 80% or more of allocated medication. Planned sub-group analyses were conducted on individuals who: (i) were not taking AChIs during the trial and (ii) had never taken Ginkgo before. The analysis was conducted using SPSS v.13 (SPSS Corporation, 2004) and STATA v.8.1 (STATA Corporation, 2003). The multiple imputation analysis was conducted using SOLAS v.3.2 (Statistical Solutions Ltd, 2001). RESULTS Figure 1 details participant flow through the trial. Recruitment took place between February 2003 and June Baseline demographic and clinical characteristics are presented in Table 2. A total of 119 GP practices agreed to recruit participants for the trial (representing 388 individual GPs). One hundred and thirty-two participants (75%) were recruited through their GP; 29 (16%) through psychiatrists and 15 (9%) from other sources (mainly other health professionals and advertisements). All analyses are reported so that a positive value favours Ginkgo and a negative value favours placebo, irrespective of the way the scale is scored. ITT analysis There was no significant interaction between the two factors of treatment group and level of follow-up. In the ANCOVA model with baseline score as a co-variate (n ¼ 176), compared to placebo, Ginkgo did not have a significant effect on outcome at 6 months on either the ADAS-Cog score (adjusted mean difference b ¼ 0.823; 95% CI 2.701, 1.055; p ¼ 0.392), the participant-rated QOL-AD score (b ¼ 0.187; 95% CI 1.542, 1.168; p ¼ 0.787) nor the carer-rated QOL-AD score (b ¼ 0.981; 95% CI 2.551, 0.589; p ¼ 0.222).
5 1226 r. mccarney ET AL. Figure 1. Participant flowchart. Analysis with evaluable data Treatment group did not have a significant effect on outcome at 6 months on either the ADAS-Cog score (n ¼ 140; b ¼ 0.608; 95%CI 2.609, 1.393; p ¼ 0.549), the participant-rated QOL-AD score (n ¼ 142; b ¼ 0.431; 95%CI 1.717, 0.856; p ¼ 0.509) nor the carer-rated QOL-AD score (n ¼ 131; b ¼ 0.963; 95%CI 2.597, 0.670; p ¼ 0.245). Per protocol analysis Treatment group did not have a significant effect on outcome at 6 months on either the ADAS-Cog score (n ¼ 104; b ¼ 1.583; 95% CI 3.972, 0.807; p ¼ 0.192), the carer-rated QOL-AD score (n ¼ 97; b ¼ 0.077; 95% CI 1.667, 1.820; p ¼ 0.931) nor the participant QOL-AD score (n ¼ 103; b ¼ 0.652; 95% CI 2.219, 0.916; p ¼ 0.411). Sub-group analyses Sub-group analyses were conducted using participants who were not on an AChI at baseline (n ¼ 118); and on those who had never taken Ginkgo before (n ¼ 135). No significant differences emerged (data not shown). The ITT analyses are only reported here. Analysis of ADAS-Cog score amongst those not on an AChI showed there was no significant effect of treatment group using imputed data (b ¼ 0.095; 95% CI 2.481, 2.291; p ¼ 0.938). Neither was there a significant effect of treatment group on carer-rated QOL-AD (b ¼ ; 95% CI 2.854, 1.323; p ¼ 0.474); or on participant-rated QOL-AD (b ¼ 0.363; 95% CI 1.981, 1.255; p ¼ 0.661). Amongst participants who had never taken Ginkgo before (n ¼ 135), there was no significant effect of treatment group on ADAS-Cog score (b ¼ 1.306; 95% CI 3.785, 1.736; p ¼ 0.304); carer-rated QOL-AD score (b ¼ ; 95% CI 2.547, 1.405; p ¼ 0.572); or participant-rated QOL-AD (b ¼ 0.983; 95% CI 2.483, 0.518; p ¼ 0.202). Secondary outcomes Global outcome, as judged by the carer in response to the question on whether they would continue with the treatment, was not found to be significantly related to treatment group (number who said yes in
6 an rct of ginkgo for dementia 1227 Table 2. Baseline demographic and clinical characteristics of participants, by treatment group Participants: total sample Characteristic Placebo group (n ¼ 88) Ginkgo group (n ¼ 88) Total sample (n ¼ 176) Mean age (7.53) 79.3 (7.77) 79.5 (7.63) Females, Males 2 56, 32 (63.6%) 51, 37 (58.0%) 107, 69 (60.8%) Ethnicity 2 White: 83 (94.3%) Mixed: 1 (1.1%) Asian: 1 (1.1%) Black: 3 (3.4%) White: 84 (95.5%) Asian: 2 (2.3%) Black: 2 (2.3%) White: 167 (94.9%) Mixed: 1 (0.6%) Asian: 3 (1.7%) Black: 5 (3.4%) Median years of education (9.0, 13.1) 10.0 (9.0, 14.0) 10.0 (9.0, 13.3) Median Indices of Multiple 17.1 (5.9, 44.2) 20.5 (7.3, 40.7) 19.0 (6.3, 43.2) Deprivation score 3 Number with Alzheimer s disease, 76, 12 (86.4%) 72, 16 (81.8%) 148, 28 (84.1%) vascular dementia diagnosis 2 Evidence of vascular pathology 2 44 (50.0%) 42 (47.7%) 86 (48.9%) Median MMSE score (13.0, 25.1) 23.0 (16.9, 26.0) 22.0 (15.0, 26.0) Mean ADAS-Cog score (10.3) 20.4 (8.2) 22.7 (9.6) Median duration of dementia in years (1.0, 8.8) 3.0 (1.2, 7.2) 3.0 (1.0, 8.0) AChI use 2 29 (33.0%) 29 (33.0%) 58 (33.0%) NSAID use 2 47 (53.4%) 51 (58.0%) 98 (55.7%) Previous Ginkgo use 2 8 (10.0%) Missing n ¼ 8 21 (25.0%) Missing n ¼ 4 29 (17.7%) Missing n ¼ 12 Mean participant-rated Qol-AD score (6.1) Missing n ¼ (5.5) Missing n ¼ (5.8) Missing n ¼ 5 Mean carer-rated Qol-AD score (6.4) Missing n ¼ (6.9) Missing n ¼ (6.6) Missing n ¼ 15 Median 12-item ZBI score (5.9, 25.3) 15.0 (5.0, 27.4) Missing n ¼ (5.4, 26.6) Missing n ¼ 3 Median EQ-VAS score (50.0, 95.0) 77.0 (44.0, 95.0) Missing n ¼ (50.0, 95.0) Participants: intensive follow-up group only Characteristic Placebo group (n ¼ 45) Ginkgo group (n ¼ 43) Total sample (n ¼ 88) Median NPI score (0.0, 29.2) Missing n ¼ (0.0, 28.5) Missing n ¼ (0.0, 28.8) Mean GERRI total score (0.42) 2.58 (0.49) 2.56 (0.45) Carers Characteristic Placebo group (n ¼ 88) Ginkgo group (n ¼ 88) Total sample (n ¼ 176) Mean age (12.9) Missing n ¼ (14.5) Missing n ¼ (13.7) Missing n ¼ 11 Females, Males 2 78, 10 (88.6%) 74, 14 (84.1%) 152, 24 (86.4%) Number who are the partner of the participant 2 43 (48.9%) 50 (56.8%) 93 (52.8%) Number who live-in 2 57 (64.8%) 58 (65.9%) 115 (65.3%) Number who are the informal (unpaid) carer 2 84 (95.5%) 85 (96.6%) 169 (96.0%) 1 Mean scores are reported with standard deviations. 2 Numbers reported with percentage of group (e.g. Ginkgo group); or percentage of females or AD sufferers respectively. 3 Median scores are reported with 10th and 90th percentiles. 4 In England and Wales, Indices of Multiple Depreivation scores are a way of quantifying the relative poverty of an area and are linked to postcodes (ODPM, 2005). the placebo group was 36 (51%) and 29 (43%) in the Ginkgo group; x 2 ¼ 0.911; df ¼ 1; p ¼ 0.340). Further secondary outcomes are detailed in Table 3. Blinding Of those carers followed up at 6 months who responded to the question on blinding, approximately half declined to guess whether their care-recipient received Ginkgo or placebo during the trial (n ¼ 66; 49%). For the remainder (n ¼ 69; 51%), blinding was effective (k ¼ 0.18; p ¼ 0.115). The researchers were also effectively blinded: of the 129 evaluable cases the researcher did not hazard a guess in approximately half (n ¼ 62) and the level of agreement in the remaining 67 was poor (k ¼ 0.081; p ¼ 0.462). Safety (adverse events and coagulation times) A total of 63 adverse events were recorded by 57 of the participants (the greatest number reported by any one individual was three). Of these, 29 were in the placebo
7 1228 r. mccarney ET AL. Table 3. Adjusted difference in means for primary and secondary outcomes Measure N Adjusted difference in means (95% CI) 1 P-value ADAS-Cog ( 2.701, 1.055) Participant-rated QOL-AD ( 1.542, 1.168) Carer-rated QOL-AD ( 2.551, 0.589) NPI ( 9.176, 0.152) NPI-D ( 5.325, 0.597) GERRI ( 0.241, 0.003) ZBI ( 2.463, 2.429) EQ-VAS ( 5.922, 2.579) Positive values favour Ginkgo. 2 No significant differences were found in the analyses with evaluable data or in the per-protocol analyses. 3 Outcome measure administered at baseline in standard follow-up group only. 4 Significant difference found in the analysis with evaluable data (n ¼ 75; B ¼ 0.142; 95% CI 0.027, 0.257; p ¼ 0.016) and in the per protocol analysis (n ¼ 51; B ¼ 0.156; 95% CI 0.033, 0.279; p ¼ 0.014); in both cases, it indicates a more favourable outcome in the placebo group. group and 28 were in the Ginkgo group. There was one fatal cerebral haemorrhage in the Ginkgo group, this was the subject of an emergency code break and was referred to the IAB, who considered that it did not justify terminating the trial. Table 4 details the MedDRA classifications of the adverse events by treatment group. There was no significant difference in clotting time at six months for participants who adhered to the treatment regime and had evaluable data (n ¼ 93; b ¼ 1.843; 95% CI 0.488, 4.133; p ¼ 0.113). DISCUSSION We found no evidence that a standard dose (120 mg daily) of high purity Ginkgo biloba conferred benefit in mild-moderate dementia over 6 months. The only significant findings (analysis with evaluable data and per protocol analysis of carer-rated function, as measured by the GERRI) favoured the placebo group. The mean difference found between the groups on the GERRI was 0.12 points, which is unlikely to be clinically significant (Erkinjuntti et al., 2002). This study was conducted independently of the pharmaceutical industry and funded by a National charity. Studies funded by the pharmaceutical industry generally show larger effect sizes compared with independent studies (Lexchin et al., 2003; Perlis et al., 2005). Strengths of this study include the use of a placebo laced with quinine, to reduce the risk of de-blinding; and standardised outcome measures to allow a direct comparison with other dementia trials. Our results suggest that Ginkgo is ineffective in this context. There are alternative explanations for our findings, although we consider them to be improbable. Because of the recruitment shortfall, type II error is a possibility but unlikely. There was no apparent trend in our results (the nonsignificant differences mostly favoured placebo) and we consider this study to have had sufficient power to reliable detect any clinically significant Table 4. MedDRA classification of the adverse events by treatment group MedDRA category Placebo group Ginkgo group Serious Total Serious Total 006 Infections and infestations Blood and lymphatic system Metabolism and nutrition Psychiatric Nervous system Ear and labyrinth Cardiac Vascular Respiratory, thoracic and mediastinal Gastrointestinal Hepatobiliary Skin and subcutaneous tissue Musculoskeletal and connective tissue Renal and urinary Reproductive system and breast Grand total
8 an rct of ginkgo for dementia 1229 KEY POINTS Despite numerous trials, the effectiveness of Ginkgo biloba in the treatment of dementia remains unclear We found no evidence that taking Ginkgo for six months improves cognition or quality of life, compared to placebo differences: the sample size we achieved would have detected a difference of 6 points on the ADAS-cog with over 90% power. The differences in baseline ADAS-Cog scores between the treatment groups were due to chance as the trial was randomised and fully concealed. All analyses took account of these differences in baseline score between groups. While it would have been of interest to conduct sub-group analyses looking at for example diagnosis, the study was not powered to do so. In this study, we only recruited participants who were able to read and write English and this may have introduced sampling bias and undermined the representativeness of the study. It was difficult to control for this however as there were no validated versions of the questionnaires we used available in the languages needed. Another possible source of sampling bias is the geographical limitations of our catchment area. In general however our sample s baseline demographics do seem similar to data presented from other dementia trials and our catchment area included a population of around 15,000,000 (ONS, 2005). The heterogeneity of the sample is a hallmark of pragmatic clinical trial design (Gartlehner et al., 2006). The importance of early intervention in the management of dementia is clear and there is a need for a safe, effective treatment that could slow down the progression of dementia and that can be used at an early stage of the disease, in a community setting. This, combined with a desire among the public to embrace complementary and alternative therapies explains the enduring interest in Ginkgo. However we are not sure whether this interest is warranted. Although Ginkgo appears safe in use we found no evidence that it provides a clinically significant benefit and we do not recommend its use in routine dementia care. CONFLICT OF INTEREST Robbert van Haselen provided some consultancy services to Schwabe Pharma in 2005, unrelated to this research. All the other authors have no conflicts of interest. ACKNOWLEDGEMENTS This study was funded by the Alzheimer s Society (grant ref: QRD/2001/01/07). Our thanks go to the following for their invaluable input into the project: Jean Barton, Patricia Best and Angela Clayton-Turner (consumer representatives of the Alzheimer s Society s Quality Research in Dementia (QRD) group); Susanne Sorensen (head of research, QRD) and Richard Harvey (former director of research, QRD); Cassie Richardson, Charmie Kodituwakku and Toria Maybey (members of the research team). REFERENCES American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR (Text Revision), 4th edn. American Psychiatric Press: Washington, DC. Bedard M, Molloy D, Squire L, et al The Zarit Burden Interview: a new short version and screening version. Gerontologist 41(5): Birks J, Grimley EV, Van Dongen M Ginkgo biloba for cognitive impairment and dementia. Cochrane Database of Systematic Reviews 4: CD Cummings J, Mega M, Gray K, et al The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 44(12): Erkinjuntti T, Kurz A, Gauthier S, et al Efficacy of galantamine in probable vascular dementia and Alzheimer s disease combined with cerebrovascular disease: a randomised trial. Lancet 359(9314): Folstein M, Folstein S, McHugh P Mini-Mental State : a practical method for grading the cognitive state of patients for the clinician. J Psychiatric Res 12: Gartlehner G, Hansen R, Nissman D, et al A simple and valid tool distinguished efficacy from effectiveness studies. J Clin Epidemiol 59: ICH International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) adopts Consolidated Guideline on Good Clinical Practice in the Conduct of Clinical Trials on Medicinal Products for Human Use. Int Digest Health Legislation 48(2): Kayne S Ginkgo biloba: potential concern. Good Clin Pract J 8(11): Lexchin J, Bero LA, Djulbegovic B, Clark O Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ 326(7400): Logsdon R, Gibbons L, McCurry S, et al Quality of life in Alzheimer s disease: patient and caregiver reports. J Mental Health Ageing 5: McCarney R, Warner J Ginkgo biloba. In Therapeutic Strategies in Dementia, Ritchie C et al. (ed). Clinical Publishing: Oxford; McCarney R, Warner J, Iliffe S, et al The Hawthorne Effect: a randomised, controlled trial. BMC Medic Res Methodol 7(30). McKhann G, Drachman D, Folstein M, et al Clinical diagnosis of Alzheimer s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and
9 1230 r. mccarney ET AL. Human Services Task Force on Alzheimer s Disease. Neurology 34: National Institute for Clinical Excellence Donepezil, Galantamine, Rivastigmine (Review) and Memantine for the Treatment of Alzheimer s Disease. NICE: London. ODPM Indices of Multiple Deprivation, Office of the Deputy Prime Minister: London. ONS Mid-2004 Population Estimates: Quinary Age Groups and Sex for Local Authorities in England and Wales; Estimated Resident Population. Office for National Statistics: London. Perlis RH, Perlis CS, Wu Y, et al Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry. Am J Psychiatry 162(10): Raskind MA, Peskind ER, Wessel T, Yuan W Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology 54(12): Rosen W, Mohs R, Davis K A new rating scale for Alzheimer s disease. Am J Psychiatry 141: Rubin DB, Schenker N Multiple imputation in health-care databases: an overview and some applications. Stat Med 10(4): Schwartz G Development and validation of the Geriatric Evaluation by Relative s Rating Instrument (GERRI). Psychologic Rep 53: The EuroQol Group EuroQol-a new facility for the measurement of health-related quality of life. Health Policy 16(3): Vale S Subarachnoid haemorrhage associated with Ginkgo biloba. Lancet 352(9121): 36. van Dongen MC, van Rossum E, Kessels AG, et al The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment: new results of a randomized clinical trial. J Am Geriatr Soc 48(10):
10
Literature Scan: Alzheimer s Drugs
Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35 Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119
More informationRESEARCH AND PRACTICE IN ALZHEIMER S DISEASE VOL 10 EADC OVERVIEW B. VELLAS & E. REYNISH
EADC BRUNO VELLAS 14/01/05 10:14 Page 1 EADC OVERVIEW B. VELLAS & E. REYNISH (Toulouse, France, EU) Bruno Vellas: The European Alzheimer's Disease Consortium is a European funded network of centres of
More informationSupplementary Online Content
Supplementary Online Content Atri A, Frölich L, Ballard C, et al. Effect of idalopirdine as adjunct to cholinesterase inhibitors on in cognition in patients with Alzheimer disease: three randomized clinical
More informationDonepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer s disease (amended)
Issue date: November 2006 (amended September 2007) Review date: September 2009 Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer s disease (amended) Includes a
More informationNATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE. Health Technology Appraisal
NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE Health Technology Appraisal Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease (Review of TA 111) Appraisal
More informationClinicalTrials.gov "Basic Results" Data Element Definitions (DRAFT)
ClinicalTrials.gov "Basic Results" Data Element Definitions (DRAFT) January 9, 2009 * Required by ClinicalTrials.gov [*] Conditionally required by ClinicalTrials.gov (FDAAA) May be required to comply with
More informationCurrent Treatments for Dementia and Future Prospects. James Warner St Charles Hospital, London
Current Treatments for Dementia and Future Prospects James Warner St Charles Hospital, London Dementia Cognitive Non-cognitive (BPSD) Memory orientation language other cognitive abilities praxis planning
More informationK. Kahle-Wrobleski 1, J.S. Andrews 1, M. Belger 2, S. Gauthier 3, Y. Stern 4, D.M. Rentz 5, D. Galasko 6
The Journal of Prevention of Alzheimer s Disease - JPAD Volume 2, Number 2, 2015 Clinical and Economic Characteristics of Milestones along the Continuum of Alzheimer s Disease: Transforming Functional
More informationClinical Trial Results Database Page 1
Clinical Trial Results Database Page 1 Sponsor Novartis Pharmaceuticals Corporation Generic Drug Name Therapeutic Area of Trial Major Depressive Disorder (MDD) Approved Indication Treatment of major depressive
More informationExecutive Summary. The Royal Australasian College of Physicians July 2012 Page 1 of 5
PBAC Review of Pharmaceutical Benefits Scheme anti-dementia drugs to treat Alzheimer s disease Submission by The Royal Australasian College of Physicians July 2012 The Royal Australasian College of Physicians
More informationKnown as both a thief and murderer,
&A Dementia Drugs: When Should They Be Stopped? Ron Keren, MD, FRCPC As presented at the University of Toronto s Primary Care Conference, Toronto, Ontario (May 25) Known as both a thief and murderer, Alzheimer
More informationDementia of the Alzheimer Type: the Drug Treatment Debate
Dementia of the Alzheimer Type: the Drug Treatment Debate I have no financial conflict of interest. Many years ago I was given a trip to San Fran and taught to use a slide set from the drug company. I
More informationFull Novartis CTRD Results Template
Full Novartis CTRD Results Template Sponsor Novartis Generic Drug Name vildagliptin Therapeutic Area of Trial Type 2 diabetes Approved Indication Type 2 diabetes Protocol Number CLAF237A23137E1 Title A
More informationGerardo Machnicki 1, Ricardo F. Allegri 1,2 *, Carol Dillon 1, Cecilia M. Serrano 1,2 and Fernando E Taragano 2 SUMMARY INTRODUCTION
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Int J Geriatr Psychiatry (2008) Published online in Wiley InterScience (www.interscience.wiley.com).2133 Cognitive, functional and behavioral factors associated
More informationEBM Journal Club: Does Ginkgo Biloba improve memory in elder group
EBM Journal Club: Does Ginkgo Biloba improve memory in elder group R2 0 Memory loss in elder >> Dementia Defination Diagnosis Prognosis 1 Why so serious? 2 Any way to improve memory in elder??? 3 Any way
More informationThe clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only.
The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only. Please note that the results reported in any single trial may not reflect the overall
More informationSponsor. Novartis Pharmaceuticals Corporation Generic Drug Name. Agomelatine Therapeutic Area of Trial. Major depressive disorder Approved Indication
Clinical Trial Results Database Page 1 Sponsor Novartis Pharmaceuticals Corporation Generic Drug Name Therapeutic Area of Trial Major depressive disorder Approved Indication Investigational drug Study
More informationIan McKeith MD, F Med Sci, Professor of Old Age Psychiatry, Newcastle University
Ian McKeith MD, F Med Sci, Professor of Old Age Psychiatry, Newcastle University Design of trials in DLB and PDD What has been learnt from previous trials in these indications and other dementias? Overview
More informationSystematic reviews and meta-analyses of observational studies (MOOSE): Checklist.
Systematic reviews and meta-analyses of observational studies (MOOSE): Checklist. MOOSE Checklist Infliximab reduces hospitalizations and surgery interventions in patients with inflammatory bowel disease:
More informationPrevious Study Return to List Next Study
A service of the U.S. National Institutes of Health Trial record 1 of 1 for: 42603ATT3013 Previous Study Return to List Next Study A Study to Evaluate Effectiveness and Safety of Prolonged Release OROS
More informationSupplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Howard R, McShane R, Lindesay J, et al. Donepezil and memantine
More informationPrevention, health promotion & early intervention in dementia
Prevention, health promotion & early intervention in dementia Alzheimer New Zealand Conference 2014 Steve Iliffe Professor of Primary Care & Older People University College London Rotorua, New Zealand
More informationClinical Trial Designs for RCTs focussing on the Treatment of Agitation in people with Alzheimer s disease
Clinical Trial Designs for RCTs focussing on the Treatment of Agitation in people with Alzheimer s disease Professor Clive Ballard Dr Byron Creese University of Exeter, UK Guardian guide for 2018: Top
More informationEfficacy and Safety of Diclofenac Potassium 25 mg Tablet Taken Three Times Daily in Subjects With Acute Joint Pain
Page 1 of 8 A service of the U.S. National Institutes of Health Try our beta test site Trial record 1 of 1 for: 853-P-401 Previous Study Return to List Next Study Efficacy and Safety of Taken Three Times
More informationMonth/Year of Review: September 2013 Date of Last Review: February 2012
Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35, Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119 Copyright 2012 Oregon State University. All Rights
More informationSetting The setting was institutional and tertiary care in London, Essex and Hertfordshire in the UK.
Cognitive stimulation therapy for people with dementia: cost-effectiveness analysis Knapp M, Thorgrimsen L, Patel A, Spector A, Hallam A, Woods B, Orrell M Record Status This is a critical abstract of
More informationGRADE. Grading of Recommendations Assessment, Development and Evaluation. British Association of Dermatologists April 2018
GRADE Grading of Recommendations Assessment, Development and Evaluation British Association of Dermatologists April 2018 Previous grading system Level of evidence Strength of recommendation Level of evidence
More informationIQWiG Reports - Commission No. A05-19B. Executive Summary
IQWiG Reports - Commission No. A05-19B Ginkgo in Alzheimer s disease 1 Executive Summary 1 Translation of the executive summary of the final report Ginkgohaltige Präparate bei Alzheimer Demenz (Version
More informationThe audit is managed by the Royal College of Psychiatrists in partnership with:
Background The National Audit of Dementia (NAD) care in general hospitals is commissioned by the Healthcare Quality Improvement Partnership on behalf of NHS England and the Welsh Government, as part of
More informationPOLICY REF NO: SABP/SERVICE IMPROVEMENT/0024 POLICY
POLICY REF NO: SABP/SERVICE IMPROVEMENT/0024 POLICY NAME OF POLICY: REASON FOR THE POLICY: WHAT THE POLICY WILL ACHIEVE: WHO NEEDS TO KNOW ABOUT IT: DATE APPROVED: VERSION NUMBER: APPROVING COMMITTEE:
More informationPFIZER INC. THERAPEUTIC AREA AND FDA APPROVED INDICATIONS: See United States Package Insert (USPI)
PFIZER INC. These results are supplied for informational purposes only. Prescribing decisions should be made based on the approved package insert. For publications based on this study, see associated bibliography.
More informationGRADE. Grading of Recommendations Assessment, Development and Evaluation. British Association of Dermatologists April 2014
GRADE Grading of Recommendations Assessment, Development and Evaluation British Association of Dermatologists April 2014 Previous grading system Level of evidence Strength of recommendation Level of evidence
More informationThe study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
More informationWhy would caregivers not want to treat their relative's Alzheimer's disease?
University of Pennsylvania ScholarlyCommons Neuroethics Publications Center for Neuroscience & Society 10-1-2003 Why would caregivers not want to treat their relative's Alzheimer's disease? Jason Karlawish
More informationCity, University of London Institutional Repository
City Research Online City, University of London Institutional Repository Citation: Hurt, C. S., Banerjee, S., Tunnard, C., Whitehead, D. L., Tsolaki, M., Mecocci, P., Kloszewska, I., Soininen, H., Vellas,
More informationMedDRA Overview A Standardized Terminology
MedDRA Overview A Standardized Terminology Patrick Revelle Director, MedDRA MSSO 6 May 2010 MedDRA is a registered trademark of the International Federation of Pharmaceutical Manufacturers and Associations
More informationDraft for Consultation
Draft for Consultation Screening for dementia: Can screening bring benefits to those with unrecognised dementia, their carers and society? An appraisal against UKNSC criteria A draft report for the UK
More informationSponsor Novartis. Generic Drug Name. NA (not existing yet) Therapeutic Area of Trial Parkinson s Disease L-dopa induced dyskinesia
Page 1 Sponsor Novartis Generic Drug Name NA (not existing yet) Therapeutic Area of Trial Parkinson s Disease L-dopa induced dyskinesia Approved Indication Investigational. Study Number CA2206 Title A
More informationSHARED CARE PROTOCOL CHOLINESTERASE INHIBITORS IN ALZHEIMER S DEMENTIA
SHARED CARE PROTOCOL CHOLINESTERASE INHIBITORS IN ALZHEIMER S DEMENTIA Introduction Alzheimer s disease is the most common cause of dementia. It is characterised by an insidious onset of global mental
More informationA Systematic Review of the Efficacy and Clinical Effectiveness of Group Analysis and Analytic/Dynamic Group Psychotherapy
A Systematic Review of the Efficacy and Clinical Effectiveness of Group Analysis and Analytic/Dynamic Group Psychotherapy Executive summary Aims of the review The main aim of the review was to assess the
More informationRecommendations on Screening for Cognitive Impairment in Older Adults 2015
Recommendations on Screening for Cognitive Impairment in Older Adults 2015 Canadian Task Force on Preventive Health Care (CTFPHC) Putting Prevention into Practice Canadian Task Force on Preventive Health
More informationPATCH Analysis Plan v1.2.doc Prophylactic Antibiotics for the Treatment of Cellulitis at Home: PATCH Analysis Plan for PATCH I and PATCH II Authors: Angela Crook, Andrew Nunn, James Mason and Kim Thomas,
More informationFOCUS: Fluoxetine Or Control Under Supervision Results. Martin Dennis on behalf of the FOCUS collaborators
FOCUS: Fluoxetine Or Control Under Supervision Results Martin Dennis on behalf of the FOCUS collaborators Background Pre clinical and imaging studies had suggested benefits from fluoxetine (and other SSRIs)
More informationCHL 5225 H Advanced Statistical Methods for Clinical Trials. CHL 5225 H The Language of Clinical Trials
CHL 5225 H Advanced Statistical Methods for Clinical Trials Two sources for course material 1. Electronic blackboard required readings 2. www.andywillan.com/chl5225h code of conduct course outline schedule
More informationEfficacy Study of Zoledronic Acid and Teriparatide Combination Therapy in Women With Osteoporosis
A service of the U.S. National Institutes of Health Trial record 1 of 1 for: CZOL446H2409 Previous Study Return to List Next Study Efficacy Study of Zoledronic Acid and Combination Therapy in Women With
More informationPsychological therapies for people with dementia who have associated depression [New 2015].
Psychological therapies for people with dementia who have associated depression [New 2015]. SCOPING QUESTION: For people with dementia and comorbid depression, do psychological interventions (including
More informationAcetylcholinesterase inhibitors: donepezil, rivastigmine, tacrine or galantamine for non-alzheimer s dementia
STEER 2002; Vol 2: No.2 Acetylcholinesterase inhibitors: donepezil, rivastigmine, tacrine or galantamine for non-alzheimer s dementia Bunmi Fajemisin Evidence search date: November 2001 www.signpoststeer.org
More informationCholinesterase inhibitors for Alzheimer s disease (Review)
Birks J This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2008, Issue 3 http://www.thecochranelibrary.com 1 T A B L E O
More informationNATIONAL INSTITUTE FOR CLINICAL EXCELLENCE SCOPE. Dementia: the management of dementia, including the use of antipsychotic medication in older people
NATIONAL INSTITUTE FOR CLINICAL EXCELLENCE 1 Guideline title SCOPE Dementia: the management of dementia, including the use of antipsychotic medication in older people 1.1 Short title Dementia 2 Background
More informationSearch for studies: ClinicalTrials.gov Identifier: NCT
ClinicalTrials.gov A service of the U.S. National Institutes of Health Search for studies: Example. "Heart attack" AND "Los Angeles" Advanced Search Help Studies by Topic Glossary Find Studies About Clinical
More informationEvidence-based pharmacotherapy of Alzheimer s disease
International Journal of Neuropsychopharmacology (2004), 7, 351 369. Copyright f 2004 CINP DOI: 10.1017/S1461145704004444 Evidence-based pharmacotherapy of Alzheimer s disease SPECIAL SERIES John Grimley
More informationTenapanor, a gastrointestinal NHE3 inhibitor, reduces serum phosphate in patients with chronic kidney disease stage 5D and hyperphosphatemia
, a gastrointestinal NHE3 inhibitor, reduces serum phosphate in patients with chronic kidney disease stage 5D and hyperphosphatemia Geoffrey A Block, 1 David P Rosenbaum, 2 Maria Leonsson-Zachrisson, 3
More informationEffectiveness of START psychological intervention in reducing abuse by dementia family carers: randomized controlled trial
Effectiveness of START psychological intervention in reducing abuse by dementia family carers: randomized controlled trial Corresponding author: Dr Claudia Cooper. Tel: 020 7679 9248. Email: c.cooper@ucl.ac.uk
More informationCombination therapy compared to monotherapy for moderate to severe Alzheimer's Disease. Summary
Combination therapy compared to monotherapy for moderate to severe Alzheimer's Disease Summary Mai 17 th 2017 Background Alzheimer s disease is a serious neurocognitive disorder which is characterized
More informationGLOSSARY OF GENERAL TERMS
GLOSSARY OF GENERAL TERMS Absolute risk reduction Absolute risk reduction (ARR) is the difference between the event rate in the control group (CER) and the event rate in the treated group (EER). ARR =
More informationThe course of neuropsychiatric symptoms in dementia. Part II: relationships among behavioural sub-syndromes and the influence of clinical variables
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Int J Geriatr Psychiatry 2005; 20: 531 536. Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/gps.1317 The course of neuropsychiatric
More informationTenapanor, a gastrointestinal NHE3 inhibitor, reduces serum phosphate in patients with chronic kidney disease stage 5D and hyperphosphatemia
, a gastrointestinal NHE3 inhibitor, reduces serum phosphate in patients with chronic kidney disease stage 5D and hyperphosphatemia Geoffrey A Block, 1 David P Rosenbaum, 2 Maria Leonsson- Zachrisson,
More informationCRITICALLY APPRAISED PAPER (CAP)
CRITICALLY APPRAISED PAPER (CAP) Li, R., Cooper, C., Barber, J., Rapaport, P., Griffin, M., & Livingston, G. (2014). Coping strategies as mediators of the effect of the START (strategies for RelaTives)
More informationexamination in the initial assessment of overdose patients
Archives of Emergency Medicine, 1988, 5, 139-145 Use of abbreviated mental status examination in the initial assessment of overdose patients K. S. MERIGIAN,1 J. R. HEDGES,1 J. R. ROBERTS,1 R. A. CHILDRESS,'
More informationThe Zarit Burden Interview: A New Short Version and Screening Version
The Gerontologist Vol. 41, No. 5, 652 657 Copyright 2001 by The Gerontological Society of America The Zarit Burden Interview: A New Short Version and Screening Version Michel Bédard, PhD, 1,2 D. William
More informationTRANSPARENCY COMMITTEE
The legally binding text is the original French version TRANSPARENCY COMMITTEE Opinion 18 December 2013 EXELON 13.3 mg/24 hours, transdermal patch B/30 sachets (CIP: 34009 268 908 1 0) Applicant: NOVARTIS
More informationAlcohol interventions in secondary and further education
National Institute for Health and Care Excellence Guideline version (Draft for Consultation) Alcohol interventions in secondary and further education NICE guideline: methods NICE guideline Methods
More informationAs people age, changes to the structure
CMAJ Guidelines CME Recommendations on screening for cognitive impairment in older adults Canadian Task Force on Preventive Health Care* CMAJ podcasts: author interview at https://soundcloud.com/cmajpodcasts/141165-guide
More informationClinical Study Synopsis for Public Disclosure
abcd Clinical Study Synopsis for Public Disclosure This clinical study synopsis is provided in line with Boehringer Ingelheim s Policy on Transparency and Publication of Clinical Study Data. The synopsis
More informationStudy Center(s): The study was conducted at 39 study sites in Japan.
SYNOPSIS Issue Date: 20 NOVEMBER 2012 Name of Sponsor/Company Janssen Pharmaceutical K. K. Name of Finished Product CONCERTA Name of Active Ingredient(s) Methylphenidate HCl Protocol No.: JNS001-JPN-A01
More informationContents. Version 1.0: 01/02/2010 Protocol# ISRCTN Page 1 of 7
Contents 1. INTRODUCTION... 2 2. STUDY SYNOPSIS... 2 3. STUDY OBJECTIVES... 2 3.1. Primary Objective... 2 3.2. Secondary Objectives... 2 3.3. Assessment of Objectives... 3 3.4. Change the Primary Objective
More informationDementia Care Pathway
Document level: West Locality Code: CC41 Issue number: 1 Dementia Care Pathway Lead executive Authors details Type of document Target audience Document purpose Medical Director Dr Anushta Sivananthan Dr
More informationMissing data in clinical trials: making the best of what we haven t got.
Missing data in clinical trials: making the best of what we haven t got. Royal Statistical Society Professional Statisticians Forum Presentation by Michael O Kelly, Senior Statistical Director, IQVIA Copyright
More informationA report for the UK National Screening Committee
Screening for dementia: Can screening bring benefits to those with unrecognised dementia, their carers and society? An appraisal against UKNSC criteria A report for the UK National Screening Committee
More informationCognitive styles sex the brain, compete neurally, and quantify deficits in autism
Cognitive styles sex the brain, compete neurally, and quantify deficits in autism Nigel Goldenfeld 1, Sally Wheelwright 2 and Simon Baron-Cohen 2 1 Department of Applied Mathematics and Theoretical Physics,
More informationTitle of Study: Evaluation of Efficacy and Safety of Galantamine in Patients With Dementia of Alzheimer's Type Who Failed to Benefit From Donepezil
SYNOPSIS Name of Sponsor/Company Name of Finished Product REMINYL Name of Active Ingredient(s) Galantamine hydrobromide Issue Date: 18 October 2013 Protocol No.: Title of Study: Evaluation of Efficacy
More informationDrugs for dementia: the first year
The Ulster Medical Journal, Volume 69, No. 2, pp. 123-127, November 2000. Drugs for dementia: the first year An audit of prescribing practice G McGirr, S A Compton Accepted 12 September 2000 SUMMARY In
More informationEvidence profile. Physical Activity. Background on the scoping question. Population/Intervention/Comparison/Outcome (PICO)
Evidence profile Q6: Is advice on physical activity better (more effective than/as safe as) than treatment as usual in adults with depressive episode/disorder with inactive lifestyles? Background on the
More informationAppendix L: Research recommendations
1 L.1 Dementia diagnosis (amyloid PET imaging) recommendation 1 Index Test Reference Test(s) Does amyloid PET imaging provide additional diagnostic value, and is it cost effective, for the diagnosis of
More informationHOW TO PREVENT COGNITIVE DECLINE.AT MCI STAGE?
EAMA CORE CURRICULUM HOW TO PREVENT COGNITIVE DECLINE.AT MCI STAGE? Sofia Duque Orthogeriatric Unit São Francisco Xavier Hospital Occidental Lisbon Hospital Center University Geriatric Unit, Faculty of
More informationFull Novartis CTRD Results Template
Full Novartis CTRD Results Template Sponsor Novartis Generic Drug Name vildagliptin Therapeutic Area of Trial Type 2 diabetes Approved Indication Type 2 diabetes Protocol Number CLAF237A23138E1 Title A
More informationAUDIT OF THE ECT SERVICE IN WALSALL UK EXCELLENCE (NICE) GUIDELINES
JPPS 2008; 5(2): 112-117 AUDIT AUDIT OF THE ECT SERVICE IN WALSALL UK AGAINST THE NATIONAL INSTITUTE OF CLINICAL EXCELLENCE (NICE) GUIDELINES Rashda Tabassum, Syed Hassan Jawed, Usman Khalid, Sarabjeet
More informationStatistical analysis plan - The Oslo Study of Clonidine in Elderly Patients with Delirium; LUCID
Statistical analysis plan - The Oslo Study of Clonidine in Elderly Patients with Delirium; LUCID Note: This statistical analysis plan was written prior to unblinding of randomisation / treatment allocation.
More informationCentocor Ortho Biotech Services, LLC
SYNOPSIS Issue Date: 17 June 2009 Name of Sponsor/Company Name of Finished Product PROCRIT Name of Active Ingredient(s) Protocol No.: PR04-15-001 Centocor Ortho Biotech Services, LLC Epoetin alfa Title
More informationPROSPERO International prospective register of systematic reviews
PROSPERO International prospective register of systematic reviews The effect of probiotics on functional constipation: a systematic review of randomised controlled trials EIRINI DIMIDI, STEPHANOS CHRISTODOULIDES,
More informationSponsor / Company: Sanofi Drug substance(s): Insulin Glargine. According to template: QSD VERSION N 4.0 (07-JUN-2012) Page 1
These results are supplied for informational purposes only. Prescribing decisions should be made based on the approved package insert in the country of prescription. Sponsor / Company: Sanofi Drug substance(s):
More informationSafinamide (Addendum to Commission A15-18) 1
IQWiG Reports Commission No. A15-41 Safinamide (Addendum to Commission A15-18) 1 Addendum Commission:A15-41 Version: 1.1 Status: 29 October 2015 1 Translation of addendum A15-41 Safinamid (Addendum zum
More informationStrategies for handling missing data in randomised trials
Strategies for handling missing data in randomised trials NIHR statistical meeting London, 13th February 2012 Ian White MRC Biostatistics Unit, Cambridge, UK Plan 1. Why do missing data matter? 2. Popular
More informationPrinciples and Methods of Intervention Research
Principles and Methods of Intervention Research NVVO, February 2, 2009 Jan G.P. Tijssen, Ph.D. Academic Medical Center - University of Amsterdam Introduction Pathophysiologic and pharmacological insight
More informationResults. NeuRA Worldwide incidence April 2016
Introduction The incidence of schizophrenia refers to how many new cases there are per population in a specified time period. It is different from prevalence, which refers to how many existing cases there
More informationProblem solving therapy
Introduction People with severe mental illnesses such as schizophrenia may show impairments in problem-solving ability. Remediation interventions such as problem solving skills training can help people
More informationJournal Club. 1. Develop a PICO (Population, Intervention, Comparison, Outcome) question for this study
Journal Club Articles for Discussion Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-pa Stroke Study Group. N Engl J Med. 1995 Dec
More informationNational Bowel Cancer Audit Supplementary Report 2011
National Bowel Cancer Audit Supplementary Report 2011 This Supplementary Report contains data from the 2009/2010 reporting period which covers patients in England with a diagnosis date from 1 August 2009
More informationSYNOPSIS (FOR NATIONAL AUTHORITY USE ONLY) INDIVIDUAL STUDY TABLE REFERRING TO PART OF THE DOSSIER
SYNOPSIS Protocol No.: RIS-USA-63 Psychosis in Alzheimer s disease (PAD) analysis Title of Study: A randomized, double-blind, placebo controlled study of risperidone for treatment of behavioral disturbances
More informationCONSORT: missing missing data guidelines, the effects on HTA monograph reporting Yvonne Sylvestre
CONSORT: missing missing data guidelines, the effects on HTA monograph reporting Yvonne Sylvestre Clinical Trials Methodology Conference, 5 th of October 2011 NWORTH North Wales Organisation for Randomised
More informationManaging agitation in dementia using non-pharmacological therapies
Managing agitation in dementia using non-pharmacological therapies Gill Livingston Lynsey Kelly, Elanor Lewis-Holmes, Gianluca Baio, Rumana Omar, Stephen Morris, Nishma Patel, Cornelius Katona, Claudia
More informationTraumatic brain injury
Introduction It is well established that traumatic brain injury increases the risk for a wide range of neuropsychiatric disturbances, however there is little consensus on whether it is a risk factor for
More informationGSK Medicine: Study Number: Title: Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment:
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
More informationScreening Summary (SS2)
15Screening SummarySS217 Aug 06 Depression in Alzheimer s Disease Study - 2 DIADS-2 Screening Summary (SS2) Keyed: ( ) Purpose: Document findings about eligibility for DIADS-2 and about medical and social
More informationPresent by Dr Phuong Leung Dr Vasiliki Orgeta Professor Martin Orrell. Division of Psychiatry University College London
The effects of carer involvement in cognitionbased interventions (CBIs) for people with dementia on carer wellbeing: a systematic review and meta-analysis Present by Dr Phuong Leung Dr Vasiliki Orgeta
More informationMethod. NeuRA Cholinesterase inhibitors August 2016
Introduction A supplementary, or adjunctive, treatment is administered in conjunction with a patient s ongoing antipsychotic therapy. (ChEI), or anticholinesterase, have been proposed as an additional
More informationHisanori Kobayashi, Takashi Ohnishi, Ryoko Nakagawa and Kazutake Yoshizawa
RESEARCH ARTICLE The comparative efficacy and safety of cholinesterase inhibitors in patients with mild-to-moderate Alzheimer s disease: a Bayesian network meta-analysis Hisanori Kobayashi, Takashi Ohnishi,
More informationResults. NeuRA Forensic settings April 2016
Introduction Prevalence quantifies the proportion of individuals in a population who have a disease during a specific time period. Many studies have reported a high prevalence of various health problems,
More informationNEUROPSYCHOMETRIC TESTS
NEUROPSYCHOMETRIC TESTS CAMCOG It is the Cognitive section of Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) The measure assesses orientation, language, memory, praxis, attention, abstract
More informationRational Medication Use in Dementia
Rational Medication Use in Dementia Stephen Thielke sthielke@u.washington.edu (206) 764 2815 I have no conflicts of interest to report. I am an employee of the federal government. The opinions in this
More information