- Email: [email protected]
ESTIMATING CLINICALLY RELEVANT CHANGE AND DIFFERENCE THRESHOLDS FOR THE CLINICAL DEMENTIA RATING: SUM OF BOXES (CDR-SB) FOR EARLY ALZHEIMER’S DISEASE
P1258
Poster Presentations: Wednesday, July 19, 2017
(MCI)/Dementia or SLUMS), and mood (BDI-II), were collected before, at midpoint, and after 8 weeks. Results: According to paired samples t-tests conducted between baseline and endpoint for the MMSE, SLUMS and BDI-II, baseline mean scores significantly improved by endpoint for all three measures: {tMMSE(16)¼-4.88, p¼.00: Mbaseline¼23.88 (SD¼5.02), Mendpoint¼26.82 (SD¼3.43); tSLUMS(9)¼-4.52, p<.001: Mbaseline¼21.40(SD¼4.27), Mendpoint¼ 26.30(SD¼3.49); tBDI-II(16)¼2.22, p<.05: Mbaseline¼14.29 (SD¼11.07), Mendpoint¼11.06(SD¼9.59)}. Regarding cognition scores, 8 subjects transitioned from MCI range to Normal, and 1 subject transitioned from Dementia to MCI. Linear regression analysis indicated a trend for significance for the baseline SLUMS, predicting 36% of the variance in depression outcome: for every 1 unit increase in SLUMS, there was a 1.3 unit decrease in depression severity. Conclusions: Eight weeks of EE-cycling significantly improves cognition and mood in a dementia-prone population of older adults coached for activation. This suggests potential for a new care standard and coaching approach for adults/seniors at risk for dementia, and strongly supports EE’s role in dementia prevention and MCI treatment. To confirm these findings, controlled studies with larger samples are warranted.
P4-012
HOW DO PEOPLE WITH MILD COGNITIVE IMPAIRMENT AND THEIR FAMILY MEMBERS DECIDE WHETHER TO ENROLL IN PRODROMAL ALZHEIMER’S DISEASE CLINICAL TRIALS?
Chelsea G. Cox, Daniel L. Gillen, Joshua D. Grill, University of California, Irvine, Irvine, CA, USA. Contact e-mail: [email protected] Background: In an effort to intervene earlier in disease,
Alzheimer’s disease (AD) clinical trials are increasingly enrolling pre-dementia populations. This includes patients meeting criteria for mild cognitive impairment (MCI), defined as memory and other cognitive problems not sufficient to impair activities of daily living. More recently, trials have enrolled MCI patients who demonstrate AD biomarkers, termed prodromal AD. Little is known about how MCI patients and their family members decide whether to participate in trials and whether this decision-making process differs for prodromal AD trials and MCI trials that do not involve biomarker testing. Methods: We will perform separate in-person interviews with 25 MCI patient participants and their study partners, recruited from the UC Irvine AD Research Center longitudinal study. We will examine (1) how MCI patients and their study partners choose whether to enroll in clinical trials and (2) potential interactions among biomarker testing, risk tolerance, and trial decision-making. Participants will be interviewed about enrollment decisions and rate their willingness to participate in six trial vignettes, including three MCI trials (no biomarker inclusion criteria) and three prodromal AD trials (with amyloid imaging criteria), with varying levels of risk (low, medium, high). Results: This study will provide critical insight to how MCI dyads approach clinical trial enrollment decisions. We will elucidate reasons MCI patients and their family members choose to enroll in clinical trials and whether this differs for trials that involve biomarker testing. We will examine the extent to which family members participate in the decision-making process. Finally, we will explore the impact of biomarker testing on risk tolerance and trial decisions.
Conclusions: To enroll in prodromal AD trials, MCI patients
must undergo AD biomarker testing. Biomarker testing may carry risk of stigma for MCI patients and deter enrollment. Alternatively, it may provide information that reduces anxiety related to diagnostic ambiguity and incentivize trial participation. Our data may inform trial design and conduct that ensure the safety of participants, hasten translational science, and maximize community trust toward research.
P4-013
ESTIMATING CLINICALLY RELEVANT CHANGE AND DIFFERENCE THRESHOLDS FOR THE CLINICAL DEMENTIA RATING: SUM OF BOXES (CDR-SB) FOR EARLY ALZHEIMER’S DISEASE
Chris J. Edgar1, Stephanie Le Scouiller1, Paul Delmar2, Howard Mackey3, Diana Rofail1, 1Roche Products Limited, Welwyn Garden City, United Kingdom; 2F. Hoffmann-La Roche, Basel, Switzerland; 3Genentech, Inc, South San Francisco, CA, USA. Contact e-mail: [email protected] Background: Minimally Clinically Important Difference (MCID)
is a key concept for interpreting clinical trial data and responder criteria provide critical information regarding patient level benefit. Methodology in this area has evolved in recent years. There is increasing recognition of the need for separate estimates of intergroup difference and intra-individual change, and consideration of demographic and clinical characteristics of the target population. Furthermore, estimates for improvement may differ from those for worsening–important in the context of progressive disease and treatment that may moderate course. The Clinical Dementia Rating (CDR) has inherent clinical relevance and a single box score increment of 0.5 or 1.0 was proposed as a mean change reflecting efficacy, and as a responder criterion for early Alzheimer’s disease (AD). There is a need to explore this using statistical approaches and clinical consensus, to generate estimates of improvement and worsening, at different stages of disease severity. Methods: Calculation of anchor and distribution-based estimates used data from ADNI, and the SCarlet RoAD (SR) (NCT01224106) and ABBY (NCT01343966) clinical trials. Separate estimates were generated for biomarker confirmed prodromal AD (pAD) and mild AD (mAD) populations. Anchor-based estimates used change in CDR-Global Score (GS) and change in MMSE-based severity as anchors, for overall improvement and worsening of disease. Distribution-based estimates included standard deviation and standard error of measurement, as effect size metrics. Results: For pAD, distribution-based estimates at baseline and for change at 12 months showed consistency between ADNI and SR (0.5xSD: ADNI 0.46 and 0.57; SR 0.49 and 0.55). Anchor-based estimates for ‘minimally worsened’ and ‘minimally improved’ (smallest change in CDR-GS) were also consistent between populations (CDR-GS change at 12 months: ADNI 2.32 and -1.03; SR 2.15 and -1.42). The number of patients in the ‘minimally improved’ group was too low to constitute a robust estimate. Conclusions: Selection of suitable anchors is crucial to generating robust estimates. These results showed that, depending on the approach used, estimates vary markedly. Due to nature of the data collected, the selection of anchors was limited. Further analyses investigating additional approaches are planned, including exploration of relationships between anchor and target measures and optimal scoring.
Poster Presentations: Wednesday, July 19, 2017
(MCI)/Dementia or SLUMS), and mood (BDI-II), were collected before, at midpoint, and after 8 weeks. Results: According to paired samples t-tests conducted between baseline and endpoint for the MMSE, SLUMS and BDI-II, baseline mean scores significantly improved by endpoint for all three measures: {tMMSE(16)¼-4.88, p¼.00: Mbaseline¼23.88 (SD¼5.02), Mendpoint¼26.82 (SD¼3.43); tSLUMS(9)¼-4.52, p<.001: Mbaseline¼21.40(SD¼4.27), Mendpoint¼ 26.30(SD¼3.49); tBDI-II(16)¼2.22, p<.05: Mbaseline¼14.29 (SD¼11.07), Mendpoint¼11.06(SD¼9.59)}. Regarding cognition scores, 8 subjects transitioned from MCI range to Normal, and 1 subject transitioned from Dementia to MCI. Linear regression analysis indicated a trend for significance for the baseline SLUMS, predicting 36% of the variance in depression outcome: for every 1 unit increase in SLUMS, there was a 1.3 unit decrease in depression severity. Conclusions: Eight weeks of EE-cycling significantly improves cognition and mood in a dementia-prone population of older adults coached for activation. This suggests potential for a new care standard and coaching approach for adults/seniors at risk for dementia, and strongly supports EE’s role in dementia prevention and MCI treatment. To confirm these findings, controlled studies with larger samples are warranted.
P4-012
HOW DO PEOPLE WITH MILD COGNITIVE IMPAIRMENT AND THEIR FAMILY MEMBERS DECIDE WHETHER TO ENROLL IN PRODROMAL ALZHEIMER’S DISEASE CLINICAL TRIALS?
Chelsea G. Cox, Daniel L. Gillen, Joshua D. Grill, University of California, Irvine, Irvine, CA, USA. Contact e-mail: [email protected] Background: In an effort to intervene earlier in disease,
Alzheimer’s disease (AD) clinical trials are increasingly enrolling pre-dementia populations. This includes patients meeting criteria for mild cognitive impairment (MCI), defined as memory and other cognitive problems not sufficient to impair activities of daily living. More recently, trials have enrolled MCI patients who demonstrate AD biomarkers, termed prodromal AD. Little is known about how MCI patients and their family members decide whether to participate in trials and whether this decision-making process differs for prodromal AD trials and MCI trials that do not involve biomarker testing. Methods: We will perform separate in-person interviews with 25 MCI patient participants and their study partners, recruited from the UC Irvine AD Research Center longitudinal study. We will examine (1) how MCI patients and their study partners choose whether to enroll in clinical trials and (2) potential interactions among biomarker testing, risk tolerance, and trial decision-making. Participants will be interviewed about enrollment decisions and rate their willingness to participate in six trial vignettes, including three MCI trials (no biomarker inclusion criteria) and three prodromal AD trials (with amyloid imaging criteria), with varying levels of risk (low, medium, high). Results: This study will provide critical insight to how MCI dyads approach clinical trial enrollment decisions. We will elucidate reasons MCI patients and their family members choose to enroll in clinical trials and whether this differs for trials that involve biomarker testing. We will examine the extent to which family members participate in the decision-making process. Finally, we will explore the impact of biomarker testing on risk tolerance and trial decisions.
Conclusions: To enroll in prodromal AD trials, MCI patients
must undergo AD biomarker testing. Biomarker testing may carry risk of stigma for MCI patients and deter enrollment. Alternatively, it may provide information that reduces anxiety related to diagnostic ambiguity and incentivize trial participation. Our data may inform trial design and conduct that ensure the safety of participants, hasten translational science, and maximize community trust toward research.
P4-013
ESTIMATING CLINICALLY RELEVANT CHANGE AND DIFFERENCE THRESHOLDS FOR THE CLINICAL DEMENTIA RATING: SUM OF BOXES (CDR-SB) FOR EARLY ALZHEIMER’S DISEASE
Chris J. Edgar1, Stephanie Le Scouiller1, Paul Delmar2, Howard Mackey3, Diana Rofail1, 1Roche Products Limited, Welwyn Garden City, United Kingdom; 2F. Hoffmann-La Roche, Basel, Switzerland; 3Genentech, Inc, South San Francisco, CA, USA. Contact e-mail: [email protected] Background: Minimally Clinically Important Difference (MCID)
is a key concept for interpreting clinical trial data and responder criteria provide critical information regarding patient level benefit. Methodology in this area has evolved in recent years. There is increasing recognition of the need for separate estimates of intergroup difference and intra-individual change, and consideration of demographic and clinical characteristics of the target population. Furthermore, estimates for improvement may differ from those for worsening–important in the context of progressive disease and treatment that may moderate course. The Clinical Dementia Rating (CDR) has inherent clinical relevance and a single box score increment of 0.5 or 1.0 was proposed as a mean change reflecting efficacy, and as a responder criterion for early Alzheimer’s disease (AD). There is a need to explore this using statistical approaches and clinical consensus, to generate estimates of improvement and worsening, at different stages of disease severity. Methods: Calculation of anchor and distribution-based estimates used data from ADNI, and the SCarlet RoAD (SR) (NCT01224106) and ABBY (NCT01343966) clinical trials. Separate estimates were generated for biomarker confirmed prodromal AD (pAD) and mild AD (mAD) populations. Anchor-based estimates used change in CDR-Global Score (GS) and change in MMSE-based severity as anchors, for overall improvement and worsening of disease. Distribution-based estimates included standard deviation and standard error of measurement, as effect size metrics. Results: For pAD, distribution-based estimates at baseline and for change at 12 months showed consistency between ADNI and SR (0.5xSD: ADNI 0.46 and 0.57; SR 0.49 and 0.55). Anchor-based estimates for ‘minimally worsened’ and ‘minimally improved’ (smallest change in CDR-GS) were also consistent between populations (CDR-GS change at 12 months: ADNI 2.32 and -1.03; SR 2.15 and -1.42). The number of patients in the ‘minimally improved’ group was too low to constitute a robust estimate. Conclusions: Selection of suitable anchors is crucial to generating robust estimates. These results showed that, depending on the approach used, estimates vary markedly. Due to nature of the data collected, the selection of anchors was limited. Further analyses investigating additional approaches are planned, including exploration of relationships between anchor and target measures and optimal scoring.