Supplemental Evidence and Data Request on Diagnostic and Treatment of Clinical Alzheimer's-Type Dementia (CATD), 64837-64843 [2018-27361]

Download as PDF Federal Register / Vol. 83, No. 242 / Tuesday, December 18, 2018 / Notices for databases released through the HCUP Central Distributor depending on the type of database. The fee for sale of state-level data is determined by each participating Statewide Data Organization and reimbursed to those organizations. Information collected in the HCUP Application process will be used for two purposes only: 1. Business Transaction: In order to deliver the HCUP databases and software, contact information is necessary for shipping some types of HCUP data on disk (or any other media used in the future). 2. Enforcement of the HCUP DUA: The HCUP DUA contains several restrictions on use of the data. Most of these restrictions have been put in place to safeguard the privacy of individuals and establishments represented in the data. For example, data users can only use the data for research, analysis, and aggregate statistical reporting and are prohibited from attempting to identify any persons in the data. Contact information on HCUP DUAs is retained in the event that a violation of the DUA takes place. 64837 Estimated Annual Respondent Burden Exhibit 1 shows the estimated annualized burden associated with the applicants’ time to order any of the HCUP databases. An estimated 1,500 persons will order HCUP data annually. Each of these persons will complete an application (10 minutes), the DUA training (15 minutes) and a DUA (5 minutes). The total burden is estimated to be 750 hours annually. Exhibit 2 shows the estimated annualized cost burden associated with the applicants’ time to order HCUP data. The total cost burden is estimated to be $29,662 annually. EXHIBIT 1—ESTIMATED ANNUALIZED BURDEN HOURS Number of respondents Form name Number of responses per respondent Hours per response Total burden hours HCUP Application Form .................................................................. HCUP DUA Training ....................................................................... HCUP DUA ..................................................................................... 1,500 1,500 1,500 1 .............................. 1 .............................. 1 .............................. 10/60 ..................... 15/60 ..................... 5/60 ....................... 250 375 125 Total ......................................................................................... 4,500 na ............................ na .......................... 750 EXHIBIT 2—ESTIMATED ANNUALIZED COST BURDEN Number of respondents Form name Total burden hours Average hourly wage rate * Total cost burden HCUP Application Form ....................................................................... HCUP DUA Training ............................................................................ HCUP DUA .......................................................................................... 1,500 1,500 1,500 250 ....................... 375 ....................... 125 ....................... $39.55 ................. 39.55 ................... 39.55 ................... $9,887 14,831 4,944 Total ..................................................................................................... 4,500 750 ....................... na ........................ 29,662 * Based upon the mean of the average wages for Life Scientists, All Other (19–1099), National Compensation Survey: Occupational Employment Statistics, May 2017 National Occupational Employment and Wage Estimates United States, U.S. Department of Labor, Bureau of Labor Statistics. http://www.bls.gov/oes/current/oes_nat.htm#b29-0000. amozie on DSK3GDR082PROD with NOTICES Request for Comments In accordance with the Paperwork Reduction Act, comments on AHRQ’s information collection are requested with regard to any of the following: (a) Whether the proposed collection of information is necessary for the proper performance of AHRQ health care research and health care information dissemination functions, including whether the information will have practical utility; (b) the accuracy of AHRQ’s estimate of burden (including hours and costs) of the proposed collection(s) of information; (c) ways to enhance the quality, utility, and clarity of the information to be collected; and (d) ways to minimize the burden of the collection of information upon the respondents, including the use of automated collection techniques or other forms of information technology. Comments submitted in response to this notice will be summarized and included in the Agency’s subsequent VerDate Sep<11>2014 00:45 Dec 18, 2018 Jkt 247001 request for OMB approval of the proposed information collection. All comments will become a matter of public record. Francis D. Chesley, Jr., Acting Deputy Director. [FR Doc. 2018–27359 Filed 12–17–18; 8:45 am] BILLING CODE 4160–90–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Agency for Healthcare Research and Quality Supplemental Evidence and Data Request on Diagnostic and Treatment of Clinical Alzheimer’s-Type Dementia (CATD) Agency for Healthcare Research and Quality (AHRQ), HHS. ACTION: Request for supplemental evidence and data submissions. AGENCY: PO 00000 Frm 00029 Fmt 4703 Sfmt 4703 The Agency for Healthcare Research and Quality (AHRQ) is seeking scientific information submissions from the public. Scientific information is being solicited to inform our review of Diagnostic and Treatment of Clinical Alzheimer’s-type Dementia (CATD), which is currently being conducted by the AHRQ’s Evidence-based Practice Centers (EPC) Program. Access to published and unpublished pertinent scientific information will improve the quality of this review. DATES: Submission Deadline on or before January 17, 2019. ADDRESSES: Email submissions: epc@ahrq.hhs.gov. Print submissions: Mailing Address: Center for Evidence and Practice Improvement, Agency for Healthcare Research and Quality, ATTN: EPC SEADs Coordinator, 5600 Fishers Lane, Mail Stop 06E53A, Rockville, MD 20857. SUMMARY: E:\FR\FM\18DEN1.SGM 18DEN1 64838 Federal Register / Vol. 83, No. 242 / Tuesday, December 18, 2018 / Notices amozie on DSK3GDR082PROD with NOTICES Shipping Address (FedEx, UPS, etc.): Center for Evidence and Practice Improvement, Agency for Healthcare Research and Quality, ATTN: EPC SEADs Coordinator, 5600 Fishers Lane, Mail Stop 06E77D, Rockville, MD 20857. FOR FURTHER INFORMATION CONTACT: Jenae Benns, Telephone: 301–427–1496 or Email: epc@ahrq.hhs.gov. SUPPLEMENTARY INFORMATION: The Agency for Healthcare Research and Quality has commissioned the Evidence-based Practice Centers (EPC) Program to complete a review of the evidence for Diagnostic and Treatment of Clinical Alzheimer’s-type Dementia (CATD). AHRQ is conducting this systematic review pursuant to Section 902(a) of the Public Health Service Act, 42 U.S.C. 299a(a). The EPC Program is dedicated to identifying as many studies as possible that are relevant to the questions for each of its reviews. In order to do so, we are supplementing the usual manual and electronic database searches of the literature by requesting information from the public (e.g., details of studies conducted). We are looking for studies that report on Diagnostic and Treatment of Clinical Alzheimer’s-type Dementia (CATD), including those that describe adverse events. The entire research protocol, including the key questions, is also available online at: https:// effectivehealthcare.ahrq.gov/topics/ alzheimers-type-dementia/protocol. This is to notify the public that the EPC Program would find the following information on Diagnostic and Treatment of Clinical Alzheimer’s-type Dementia (CATD) helpful: D A list of completed studies that your organization has sponsored for this indication. In the list, please indicate whether results are available on ClinicalTrials.gov along with the ClinicalTrials.gov trial number. D For completed studies that do not have results on ClinicalTrials.gov, please provide a summary, including the following elements: study number, study period, design, methodology, indication and diagnosis, proper use instructions, inclusion and exclusion criteria, primary and secondary outcomes, baseline characteristics, number of patients screened/eligible/ enrolled/lost to follow-up/withdrawn/ analyzed, effectiveness/efficacy, and safety results. D A list of ongoing studies that your organization has sponsored for this indication. In the list, please provide the ClinicalTrials.gov trial number or, if the trial is not registered, the protocol for the study including a study number, the study period, design, methodology, indication and diagnosis, proper use instructions, inclusion and exclusion criteria, and primary and secondary outcomes. VerDate Sep<11>2014 00:45 Dec 18, 2018 Jkt 247001 D Description of whether the above studies constitute ALL Phase II and above clinical trials sponsored by your organization for this indication and an index outlining the relevant information in each submitted file. Your contribution will be very beneficial to the EPC Program. Materials submitted must be publicly available or able to be made public. Materials that are considered confidential; marketing materials; study types not included in the review; or information on indications not included in the review cannot be used by the EPC Program. This is a voluntary request for information, and all costs for complying with this request must be borne by the submitter. The draft of this review will be posted on AHRQ’s EPC Program website and available for public comment for a period of 4 weeks. If you would like to be notified when the draft is posted, please sign up for the email list at: https://www.effective healthcare.ahrq.gov/email-updates. The systematic review will answer the following questions. This information is provided as background. AHRQ is not requesting that the public provide answers to these questions. The Key Questions KQ 1: In adults with CATD, what are the efficacy and harms of prescription pharmacological interventions versus placebo/inactive control for treatment of cognition, function, and quality of life? KQ 1a: In adults with CATD, does the efficacy of prescription pharmacological interventions versus placebo/inactive control vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pretreatment cognitive or functional level/CATD stage, living setting)? KQ 2: In adults with CATD, what are the efficacy and harms of nonprescription pharmacological interventions versus placebo/inactive control for treatment of cognition, function, and quality of life? KQ 2a: In adults with CATD, does the efficacy of nonprescription pharmacological interventions versus placebo/inactive control vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pretreatment cognitive or functional level/CATD stage, living setting)? KQ 3: In adults with CATD, what are the comparative effectiveness and harms of prescription pharmacological interventions versus other active interventions for treatment of cognition, function, and quality of life? KQ 3a: In adults with CATD, what are the comparative effectiveness and harms of prescription pharmacological interventions versus other prescription pharmacological interventions for treatment of cognition, function, and quality of life? KQ 3b: In adults with CATD, what are the comparative effectiveness and harms of prescription pharmacological interventions versus nonprescription pharmacological PO 00000 Frm 00030 Fmt 4703 Sfmt 4703 interventions for treatment of cognition, function, and quality of life? KQ 3c: In adults with CATD, what are the comparative effectiveness and harms of prescription pharmacological interventions versus nonpharmacological interventions for treatment of cognition, function, and quality of life? KQ 3d: In adults with CATD, does the comparative effectiveness of prescription pharmacological interventions versus other active interventions for treatment of cognition, function, and quality of life vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pretreatment cognitive or functional level/CATD stage, living setting)? KQ 4: In adults with CATD and behavioral and psychological symptoms of dementia (BPSD), what are the efficacy and harms of prescription pharmacological interventions versus placebo/inactive control for treatment of BPSD? KQ 4a: In adults with CATD and BPSD, what are the efficacy and harms of prescription pharmacological interventions versus placebo/inactive control for reducing frequency and severity of future BPSD? KQ 4b: In adults with CATD and BPSD, does the efficacy of prescription pharmacological interventions versus placebo/inactive control for reducing frequency and severity of future BPSD vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pretreatment cognitive or functional level/CATD stage, pre-treatment BPSD severity, living setting)? KQ 4c: In adults with CATD and BPSD, what are the efficacy and harms of prescription pharmacological interventions versus placebo/inactive control for acute treatment of BPSD? KQ 4d: In adults with CATD and BPSD, does the efficacy of prescription pharmacological interventions versus placebo/inactive control for acute treatment of BPSD vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pre-treatment cognitive or functional level/CATD stage, pre-treatment BPSD severity, living setting)? KQ 5: In adults with CATD and BPSD, what are the efficacy and harms of nonprescription pharmacological interventions versus placebo/inactive control for treatment of BPSD in adults with CATD and BPSD? KQ 5a: In adults with CATD and BPSD, what are the efficacy and harms of nonprescription pharmacological interventions versus placebo/inactive control for reducing frequency and severity of future BPSD? KQ 5b: In adults with CATD and BPSD, does the efficacy of nonprescription pharmacological interventions versus placebo/inactive control for reducing frequency and severity of future BPSD vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pretreatment cognitive or functional level/CATD stage, pre-treatment BPSD severity, living setting)? KQ 5c: In adults with CATD and BPSD, what are the efficacy and harms of E:\FR\FM\18DEN1.SGM 18DEN1 Federal Register / Vol. 83, No. 242 / Tuesday, December 18, 2018 / Notices amozie on DSK3GDR082PROD with NOTICES nonprescription pharmacological interventions versus placebo/inactive control for acute treatment of BPSD? KQ 5d: In adults with CATD and BPSD, does the efficacy of nonprescription pharmacological interventions versus placebo/inactive control for acute treatment of BPSD vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pre-treatment cognitive or functional level/CATD stage, pre-treatment BPSD severity, living setting)? KQ 6: In adults with CATD and BPSD, what are the comparative effectiveness and harms of prescription pharmacological interventions versus other active interventions for treatment of BPSD? KQ 6a: In adults with CATD and BPSD, what are the comparative effectiveness and harms of prescription pharmacological interventions versus other prescription pharmacological interventions for reducing frequency and severity of future BPSD? KQ 6b: In adults with CATD and BPSD, what are the comparative effectiveness and harms of prescription pharmacological interventions versus nonprescription pharmacological interventions for reducing frequency and severity of future BPSD? KQ 6c: In adults with CATD and BPSD, what are the comparative effectiveness and harms of prescription pharmacological interventions versus nonpharmacological VerDate Sep<11>2014 00:45 Dec 18, 2018 Jkt 247001 interventions for reducing frequency and severity of future BPSD? KQ 6d: In adults with CATD and BPSD, does the comparative effectiveness of prescription pharmacological interventions versus other active interventions for reducing frequency and severity of future BPSD vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, depression, pretreatment cognitive or functional level/CATD stage, pre-treatment BPSD severity, living setting)? KQ 6e: In adults with CATD and BPSD, what are the comparative effectiveness and harms of prescription pharmacological interventions versus other prescription pharmacological interventions for acute treatment of BPSD? KQ 6f: In adults with CATD and BPSD, what are the comparative effectiveness and harms of prescription pharmacological interventions versus nonprescription pharmacological interventions for acute treatment of BPSD? KQ 6g: In adults with CATD and BPSD, what are the comparative effectiveness and harms of prescription pharmacological interventions versus nonpharmacological interventions for acute treatment of BPSD? KQ 6h: In adults with CATD and BPSD, does the comparative effectiveness of prescription pharmacological interventions versus other active interventions for acute treatment of BPSD vary as a function of PO 00000 Frm 00031 Fmt 4703 Sfmt 4703 64839 patient characteristics (i.e., age, sex, race/ ethnicity, depression, pre-treatment cognitive or functional level/CATD stage, pre-treatment BPSD severity, living setting)? KQ 7: In adults with suspected CATD, what are the accuracy, comparative accuracy, and harms of different individual cognitive diagnostic tests and their combinations for making the diagnosis of CATD as defined by full clinical evaluation and/or neuropsychological testing with explicit diagnostic criteria? KQ 7a: Do the accuracy and comparative accuracy of cognitive tests for making the diagnosis of CATD as defined by full clinical evaluation and/or neuropsychological testing with explicit diagnostic criteria vary as a function of patient characteristics (i.e., age, sex, race/ethnicity, education, pre-testing cognitive or functional level CATD stage)? KQ 8: In adults with a clinical diagnosis of CATD, what are the accuracy, comparative accuracy, and harms of brain imaging, CSF, and blood tests for diagnosing pathologically confirmed Alzheimer’s disease as the underlying etiology? KQ 8a: Do the accuracy and comparative accuracy of brain imaging, CSF, and blood tests for pathologically confirmed Alzheimer’s disease as the underlying etiology of CATD vary as a function of patient characteristics (i.e., age, sex, race/ ethnicity, depression, education, pre-testing cognitive or functional level CATD stage)? E:\FR\FM\18DEN1.SGM 18DEN1 VerDate Sep<11>2014 00:45 Dec 18, 2018 KQ 4–6: Drug treatment efficacy, comparative effectiveness & harms on BPSD. KQ 1–3: Drug treatment efficacy, comparative effectiveness & harms on cognition, function & quality of life. KQ amozie on DSK3GDR082PROD with NOTICES Adults with CATD ≥50 years of age with BPSD (studies specified BPSD inclusion criterion). Patient characteristics to be assessed as possible treatment effect modifiers: Age, Sex, Race/ ethnicity, Pre-treatment cognitive or functional level/CATD stage, Pre-treatment BPSD severity, Living setting. Adults with CATD ≥50 years of age Patient characteristics to be assessed as possible treatment effect modifiers: Age, Sex, Race/ ethnicity, Depression, Pre-treatment cognitive or functional level/ CATD stage, Living setting. Population Prescription pharmacologic treatment: Cholinesterase inhibitors, NMDA antagonists, Antipsychotics, second generation (any) and first generation (only haloperidol), Antidepressants, Anti-seizure/mood stabilizers, Anxiolytics, benzodiazepine, Anxiolytics, other Hormonal agents (Disinhibited sexual behavior only), Cannabinoids, Combinations. Nonprescription pharmacologic treatment: OTC supplements, Vitamins, Herbals. Prescription pharmacologic (drug) treatment: Cholinesterase inhibitors, NMDA antagonists. Nonprescription pharmacologic (drug) treatment: OTC supplements, Vitamins, Herbals. Intervention Jkt 247001 Efficacy comparisons: Placebo, Other inactive control. Comparative effectiveness comparisons: Prescription drug treatment, Nonprescription drug treatment, Nondrug treatment. For efficacy comparisons: Placebo, Other inactive control. For comparative effectiveness comparisons: Prescription drug treatment, Nonprescription drug treatment, Nondrug treatment. Treatment comparator or diagnostic reference standard Efficacy and comparative effectiveness: Change in patient cognition (global screen, multidomain, memory, executive function, language, attention), function, or QOL on validated test. Change in disease stage based on validated test. Change in patient ‘‘at home’’ IADL or ADL function. Change in patient residence to different level of independence. Harms: General: FDA defined SAEs, Withdrawals due to AEs. Psychiatric: Somnolence, Confusion/ Delirium. Nonpsychiatric: Falls, Extrapyramidal symptoms, Stroke. Mortality (all-cause, CVD, non-CVD). Efficacy and comparative effectiveness: Primary: Change in the frequency and/or severity of patient BPSD* on validated tests, Agitation/aggression, Psychosis, Depression, Anxiety, Disinhibited sexual behavior, Change in patient QoL on validated test, Change in validated general behavior scale. Secondary: Change in caregiver/ staff outcomes on validated tests, Depression, Global stress/distress, QOL, Burden. Harms: General: FDA defined composite SAE outcome, Withdrawals due to AE. Psychiatric: Somnolence, Confusion/ Delirium. Nonpsychiatric: Falls, Extrapyramidal symptoms, Stroke, Mortality (allcause, CVD, non-CVD). Health outcomes & harms Timing Agitation, aggression, psychosis or Disinhibited sexual behavior outcomes: ≥2 weeks. Depression or anxiety outcomes: ≥24 weeks. ≥24 weeks ..................... TABLE 1—PICOTS [Populations, interventions, comparators, outcomes, timing, settings/study design] Community-dwelling, Assisted living, Nursing home. Cognitive outcomes: Community-dwelling, Assisted living. Functional & QOL outcomes: Communitydwelling, Assisted living, Nursing home. Setting Efficacy and comparative effectiveness: RCT, CCT, systematic review of RCTs or CCTs. Harms: RCT, CCT, controlled prospective cohort studies ≥1,000 participants, systematic review of any of these study designs. Efficacy and comparative effectiveness: RCT, CCT, systematic review of RCTs or CCTs. Harms: RCT, CCT, controlled prospective cohort studies with ≥1,000 participants, systematic review of any of these study designs. Study design 64840 Federal Register / Vol. 83, No. 242 / Tuesday, December 18, 2018 / Notices PO 00000 Frm 00032 Fmt 4703 Sfmt 4703 E:\FR\FM\18DEN1.SGM 18DEN1 VerDate Sep<11>2014 00:45 Dec 18, 2018 Jkt 247001 Cognitive tests: Adults ≥50 years of age with suspected CATD. Biomarker tests only: Adults ≥50 years of age with clinical syndrome of CATD. Patient characteristics to be assessed as possible effect modifiers of diagnostic test accuracy: Age, Sex, Race/ethnicity, Education, Depression. Pre-test cognitive or functional level/ CATD stage. Brief, validated cognitive tests: Global (brief screens, multi-domain batteries), Single domain tests (memory, executive, language, attention. Biomarker tests: Brain imaging: CT/MRI: Medial temporal atrophy/hippocampal volume, Cortical thickness, DTI indices PET: 18F-FDG PET, Amyloid PET, 11C-PiB and fluorinated tracers (e.g. florbetapir, flutemetamol, florbetaben), Tau PET fMRI: Resting state and task specific activation SPECT: Resting state cerebral perfusion CSF tests: Ab42, Ab42/Ab40 ratio, ttau, p-tau, t-tau/Ab42 ratio, p-tau/ Ab42 ratio, neurofilament light protein Blood tests: Ab42, Ab42/Ab40 ratio, APP Combinations Cognitive tests: Full clinical evaluation and/or neuropsychological testing with explicit diagnostic criteria. Biomarker tests: Postmortem neuropathological confirmation of AD. Accuracy and comparative accuracy (e.g., TP, FP, TN, FN, sensitivity, specificity, PPV, NPV). Of cognitive tests for confirming clinical syndrome of CATD. Of biomarker tests for confirming that etiology of CATD is AD. Harms: Psychological or behavioral True positive: Labeling stigma False positive: Incorrect diagnosis, Labeling stigma, Side effects of unneeded interventions (e.g., restrictions on independence). False negative: Unexplained symptoms, Failure to make appropriate interventions (e.g., safety precautions, future planning). Any test result: Patient or caregiver mental distress. Physical: Directly from diagnostic tests: Pain, Infection, Headache, Radiation. Any ................................ Community-dwelling, Assisted living. Accuracy and comparative accuracy: Controlled observational studies (i.e., crosssectional, retrospective cohort, case control); systematic review of controlled observational studies. Harms: Controlled observational studies (i.e., crosssectional, retrospective cohort, case control, prospective cohort); systematic review of controlled observational studies. * For this report, two psychological symptoms that are components of BPSD have been excluded due to their coverage in recent, high quality systematic reviews—apathy and sleep disturbances.18 19 In addition, wandering was also eliminated, as this symptom is usually treated with nonpharmacologic interventions, which are not covered as interventions in this review. † Strength of evidence (SOE) will be evaluated for the 1–2 most commonly reported validated treatment efficacy outcomes for each of the following test categories: disease stage, global cognitive screening tests, global multidomain cognitive tests, memory, executive functioning, language, attention, function, quality of life, BPSD agitation/aggression, and the harms outcome of serious adverse events. Additional treatment outcomes will be considered for SOE grading when available data allow. For diagnostic tests, SOE will be graded for the 1–2 most commonly reported validated tests for each of the following categories: global cognitive screening tests, global multidomain cognitive tests, memory, MRI, PET, and CSF tests. Additional diagnostic testing outcomes will be considered for SOE grading when available data allow. A+ = beta amyloid, AD = Alzheimer’s dementia, ADL = activities of daily living, AE = adverse events, APOE = apolipoprotein E, APP = amyloid precursor protein, BPSD = behavioral and psychological symptoms of dementia, CATD = clinical Alzheimer’s-type dementia, CCT = controlled clinical trial, CSF = cerebrospinal fluid, CT = computed tomography, CVD = cardiovascular disease, DTI = diffusion tensor imaging, FDG = fluorodeoxyglucose, fMRI = functional magnetic resonance imaging, FN = false negative, FP = false positive, IADL = instrumental activities of daily living, MCI = mild cognitive impairment, MRI = magnetic resonance imaging, NMDA = N-methyl-D-aspartate, NPV = negative predictive value, OTC = over-the-counter, PET = positron emission tomography, PPV = positive predictive value, p-tau = abnormally phosphorylated tau, QOL = quality of life, RCT = randomized clinical trial, ROC = receiver operating characteristic, SAE = serious adverse events, SPECT = single-photon emission computed tomography, TN = true negative, TP = true positive, t-tau = total tau. KQ 7–8: Diagnostic test accuracy & harms (also see Table 2 below). amozie on DSK3GDR082PROD with NOTICES Federal Register / Vol. 83, No. 242 / Tuesday, December 18, 2018 / Notices PO 00000 Frm 00033 Fmt 4703 Sfmt 4703 E:\FR\FM\18DEN1.SGM 18DEN1 64841 64842 Federal Register / Vol. 83, No. 242 / Tuesday, December 18, 2018 / Notices TABLE 2—PRESCRIPTION DRUGS USED FOR TREATMENT OF CATD COGNITION, FUNCTION, QUALITY OF LIFE OR BPSD Class of drug Drug name(s) Cholinesterase inhibitor ............................................................................ NMDA receptor antagonist ....................................................................... Cholinesterase inhibitor/NMDA receptor antagonist combination ............ 1st generation (typical) antipsychotic ....................................................... 2nd generation (atypical) antipsychotic .................................................... Anti-depressant, selective serotonin-reuptake inhibitor (SSRI) ............... Donepezil *, rivastigmine *, galantamine *. Memantine *. Donepezil/Memantine *. only Haloperidol. e.g., Risperidone, quetiapine, olanzapine, aripiprazole, clozapine. e.g., Citalopram, escitalopram, sertraline, fluoxetine, fluvoxamine, paroxetine. e.g., Duloxetine, venlafaxine. e.g., Trazodone, bupropion, mirtazapine. e.g., Valproate, gabapentin, carbamazepine, lamotrigine. e.g., Clonazepam, diazepam, lorazepam, temazepam, alprazolam. Buspirone. Dextromethorpan/Quinidine. e.g., medroxyprogesterone acetate, cyproterone acetate, leuprolide. Anti-depressant, serotonin-norepinephrine reuptake inhibitor (SNRI) ..... Anti-depressant, other † ............................................................................ Anti-seizure/mood stabilizer ..................................................................... Anti-anxiety, benzodiazepine .................................................................... Anti-anxiety, other ..................................................................................... Mixed ........................................................................................................ Hormones (antiandrogens, estrogens, gonadotropin-releasing hormone analogues). Cannabinoids ............................................................................................ e.g., medical marijuana. * US FDA approved indication for Alzheimer’s dementia. † Excludes MAO-inhibitor, tricyclic and tetracyclic antidepressants. BPSD = behavioral and psychological symptoms of dementia, CATD = clinical Alzheimer’s-type dementia, NMDA = N-methyl-D-aspartate, SSRI = selective serotonin reuptake inhibitor, SNRI = selective norepinephrine reuptake inhibitor. amozie on DSK3GDR082PROD with NOTICES References 1. Plassman BL, Langa KM, Fisher GG, et al. Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology. 2007;29(1–2):125–32. doi: 10.1159/ 000109998. PMID: 17975326. 2. Langa KM, Larson EB, Crimmins EM, et al. A Comparison of the Prevalence of Dementia in the United States in 2000 and 2012. JAMA Intern Med. 2017 Jan 01;177(1):51–8. doi: 10.1001/ jamainternmed.2016.6807. PMID: 27893041. 3. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on AgingAlzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011 May;7(3):263–9. doi: 10.1016/ j.jalz.2011.03.005. PMID: 21514250. 4. Hurd MD, Martorell P, Delavande A, et al. Monetary costs of dementia in the United States. N Engl J Med. 2013 Apr 4;368(14):1326–34. doi: 10.1056/ NEJMsa1204629. PMID: 23550670. 5. Zhao QF, Tan L, Wang HF, et al. The prevalence of neuropsychiatric symptoms in Alzheimer’s disease: Systematic review and meta-analysis. J Affect Disord. 2016 Jan 15;190:264–71. doi: 10.1016/j.jad.2015.09.069. PMID: 26540080. 6. What is Alzheimer’s? Alzheimer’s Association. www.alz.org/alzheimersdementia/what-is-alzheimers. Accessed on November 2, 2018. 7. Alzheimer’s Disease. Centers for Disease Control and Prevention. www.cdc.gov/ aging/aginginfo/alzheimers.htm. Accessed on November 2, 2018. 8. Association AP. Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM–IIIR); 1987. 9. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS–ADRDA VerDate Sep<11>2014 00:45 Dec 18, 2018 Jkt 247001 Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984 Jul;34(7):939– 44. PMID: 6610841. 10. Association AP. Diagnostic and Statistical Manual of Mental Disorders: DSM–5; 2013. 11. Cure S, Abrams K, Belger M, et al. Systematic literature review and metaanalysis of diagnostic test accuracy in Alzheimer’s disease and other dementia using autopsy as standard of truth. J Alzheimers Dis. 2014;42(1):169–82. doi: 10.3233/JAD–131559. PMID: 24840572. 12. Frisoni GB, Boccardi M, Barkhof F, et al. Strategic roadmap for an early diagnosis of Alzheimer’s disease based on biomarkers. Lancet Neurol. 2017 Aug;16(8):661–76. doi: 10.1016/S1474– 4422(17)30159–X. PMID: 28721928. 13. Kane RLB, M.; Fink, H.A.; Brasure, M.; Davila, H.; Desai, P.; Jutkowitz, E.; McCreedy, E.; Nelson, V.A.; McCarten, J.R.; Calvert, C.; Ratner, E.; Hemmy, L.S.; Barclay, T. Interventions To Prevent AgeRelated Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer’s-Type Dementia. AHRQ Publication No. 17–EHC008–EF. Rockville, MD: Quality AfHRa; February 2017 2017. www.effectivehealthcare.ahrq.gov/ reports/final.cfm 14. Reus VI, Fochtmann LJ, Eyler AE, et al. The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia. Am J Psychiatry. 2016 May 1;173(5):543– 6. doi: 10.1176/appi.ajp.2015.173501. PMID: 27133416. 15. Brasure M, Jutkowitz E, Fuchs E, et al. Nonpharmacologic Interventions for Agitation and Aggression in Dementia. Rockville (MD); 2016. 16. Qaseem A, Snow V, Cross JT, Jr., et al. Current pharmacologic treatment of dementia: a clinical practice guideline from the American College of Physicians PO 00000 Frm 00034 Fmt 4703 Sfmt 4703 and the American Academy of Family Physicians. Ann Intern Med. 2008 Mar 4;148(5):370–8. PMID: 18316755. 17. Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. BMJ. 2015 Mar 2;350:h369. doi: 10.1136/bmj.h369. PMID: 25731881. 18. Ruthirakuhan MT, Herrmann N, Abraham EH, et al. Pharmacological interventions for apathy in Alzheimer’s disease. Cochrane Database Syst Rev. 2018 May 4;5:CD012197. doi: 10.1002/ 14651858.CD012197.pub2. PMID: 29727467. 19. McCleery J, Cohen DA, Sharpley AL. Pharmacotherapies for sleep disturbances in dementia. Cochrane Database Syst Rev. 2016 Nov 16;11:CD009178. doi: 10.1002/ 14651858.CD009178.pub3. PMID: 27851868. 20. Hackshaw A. Small studies: strengths and limitations. Eur Respir J. 2008 Nov;32(5):1141–3. doi: 10.1183/ 09031936.00136408. PMID: 18978131. 21. Viswanathan M, Ansari M, Berkman N, et al. Assessing the Risk of Bias of Individual Studies in Systematic Reviews of Health Care Interventions AHRQ. 2012. 22. Methods Guide for Medical Test Reviews. AHRQ Publication No. 12–EC017. Rockville, MD: Quality AfHRa; June 2012. www.effectivehealthcare.ahrq.gov/ reports/final.cfm. 23. Whiting PF, Rutjes AW, Westwood ME, et al. QUADAS–2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011 Oct 18;155(8):529–36. doi: 10.7326/ 0003–4819–155–8–201110180–00009. PMID: 22007046. 24. Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 2017 Sep 21;358:j4008. doi: 10.1136/ bmj.j4008. PMID: 28935701. E:\FR\FM\18DEN1.SGM 18DEN1 Federal Register / Vol. 83, No. 242 / Tuesday, December 18, 2018 / Notices 25. Fu R, Gartlehner G, Grant M, et al. Conducting quantitative synthesis when comparing medical interventions: AHRQ and the Effective Health Care Program. J Clin Epidemiol. 2011 Nov;64(11):1187– 97. doi: 10.1016/j.jclinepi.2010.08.010. PMID: 21477993. 26. Takwoingi Y. Meta-analysis of test accuracy studies in Stata: a bivariate model approach. Version 1.1. 27. Owens DK, Lohr KN, Atkins D, et al. AHRQ series paper 5: grading the strength of a body of evidence when comparing medical interventions— agency for healthcare research and quality and the effective health-care program. J Clin Epidemiol. 2010 May;63(5):513–23. doi: S0895– 4356(09)00093–6 [pii] 10.1016/ j.jclinepi.2009.03.009. PMID: 19595577. 28. Singh S, Chang SM, Matchar DB, et al. Chapter 7: grading a body of evidence on diagnostic tests. J Gen Intern Med. 2012 Jun;27 Suppl 1:S47–55. doi: 10.1007/ s11606–012–2021–9. PMID: 22648675. 29. Berkman ND, Lohr KN, Ansari M, et al. Grading the Strength of a Body of Evidence When Assessing Health Care Interventions for the Effective Health Care Program of the Agency for Healthcare Research and Quality: An Update. Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Rockville (MD); 2008. 30. Atkins D, Chang S, Gartlehner G, et al. Assessing the Applicability of Studies When Comparing Medical Interventions. Methods Guide for Effectiveness and Comparative Effectiveness Reviews. Rockville (MD); 2008. Francis D. Chesley, Jr., Acting Deputy Director. 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Sponsors must also provide notice to enrollees informing E:\FR\FM\18DEN1.SGM 18DEN1

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[Federal Register Volume 83, Number 242 (Tuesday, December 18, 2018)]
[Notices]
[Pages 64837-64843]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-27361]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Supplemental Evidence and Data Request on Diagnostic and 
Treatment of Clinical Alzheimer's-Type Dementia (CATD)

AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS.

ACTION: Request for supplemental evidence and data submissions.

-----------------------------------------------------------------------

SUMMARY: The Agency for Healthcare Research and Quality (AHRQ) is 
seeking scientific information submissions from the public. Scientific 
information is being solicited to inform our review of Diagnostic and 
Treatment of Clinical Alzheimer's-type Dementia (CATD), which is 
currently being conducted by the AHRQ's Evidence-based Practice Centers 
(EPC) Program. Access to published and unpublished pertinent scientific 
information will improve the quality of this review.

DATES: Submission Deadline on or before January 17, 2019.

ADDRESSES: 
    Email submissions: epc@ahrq.hhs.gov.
    Print submissions:
    Mailing Address: Center for Evidence and Practice Improvement, 
Agency for Healthcare Research and Quality, ATTN: EPC SEADs 
Coordinator, 5600 Fishers Lane, Mail Stop 06E53A, Rockville, MD 20857.

[[Page 64838]]

    Shipping Address (FedEx, UPS, etc.): Center for Evidence and 
Practice Improvement, Agency for Healthcare Research and Quality, ATTN: 
EPC SEADs Coordinator, 5600 Fishers Lane, Mail Stop 06E77D, Rockville, 
MD 20857.

FOR FURTHER INFORMATION CONTACT: Jenae Benns, Telephone: 301-427-1496 
or Email: epc@ahrq.hhs.gov.

SUPPLEMENTARY INFORMATION:  The Agency for Healthcare Research and 
Quality has commissioned the Evidence-based Practice Centers (EPC) 
Program to complete a review of the evidence for Diagnostic and 
Treatment of Clinical Alzheimer's-type Dementia (CATD). AHRQ is 
conducting this systematic review pursuant to Section 902(a) of the 
Public Health Service Act, 42 U.S.C. 299a(a).
    The EPC Program is dedicated to identifying as many studies as 
possible that are relevant to the questions for each of its reviews. In 
order to do so, we are supplementing the usual manual and electronic 
database searches of the literature by requesting information from the 
public (e.g., details of studies conducted). We are looking for studies 
that report on Diagnostic and Treatment of Clinical Alzheimer's-type 
Dementia (CATD), including those that describe adverse events. The 
entire research protocol, including the key questions, is also 
available online at: https://effectivehealthcare.ahrq.gov/topics/alzheimers-type-dementia/protocol.
    This is to notify the public that the EPC Program would find the 
following information on Diagnostic and Treatment of Clinical 
Alzheimer's-type Dementia (CATD) helpful:

    [ssquf] A list of completed studies that your organization has 
sponsored for this indication. In the list, please indicate whether 
results are available on ClinicalTrials.gov along with the 
ClinicalTrials.gov trial number.
    [ssquf] For completed studies that do not have results on 
ClinicalTrials.gov, please provide a summary, including the 
following elements: study number, study period, design, methodology, 
indication and diagnosis, proper use instructions, inclusion and 
exclusion criteria, primary and secondary outcomes, baseline 
characteristics, number of patients screened/eligible/enrolled/lost 
to follow-up/withdrawn/analyzed, effectiveness/efficacy, and safety 
results.
    [ssquf] A list of ongoing studies that your organization has 
sponsored for this indication. In the list, please provide the 
ClinicalTrials.gov trial number or, if the trial is not registered, 
the protocol for the study including a study number, the study 
period, design, methodology, indication and diagnosis, proper use 
instructions, inclusion and exclusion criteria, and primary and 
secondary outcomes.
    [ssquf] Description of whether the above studies constitute ALL 
Phase II and above clinical trials sponsored by your organization 
for this indication and an index outlining the relevant information 
in each submitted file.
    Your contribution will be very beneficial to the EPC Program. 
Materials submitted must be publicly available or able to be made 
public. Materials that are considered confidential; marketing 
materials; study types not included in the review; or information on 
indications not included in the review cannot be used by the EPC 
Program. This is a voluntary request for information, and all costs for 
complying with this request must be borne by the submitter.
    The draft of this review will be posted on AHRQ's EPC Program 
website and available for public comment for a period of 4 weeks. If 
you would like to be notified when the draft is posted, please sign up 
for the email list at: https://www.effectivehealthcare.ahrq.gov/email-updates.
    The systematic review will answer the following questions. This 
information is provided as background. AHRQ is not requesting that the 
public provide answers to these questions.

The Key Questions

    KQ 1: In adults with CATD, what are the efficacy and harms of 
prescription pharmacological interventions versus placebo/inactive 
control for treatment of cognition, function, and quality of life?
    KQ 1a: In adults with CATD, does the efficacy of prescription 
pharmacological interventions versus placebo/inactive control vary 
as a function of patient characteristics (i.e., age, sex, race/
ethnicity, depression, pre-treatment cognitive or functional level/
CATD stage, living setting)?
    KQ 2: In adults with CATD, what are the efficacy and harms of 
nonprescription pharmacological interventions versus placebo/
inactive control for treatment of cognition, function, and quality 
of life?
    KQ 2a: In adults with CATD, does the efficacy of nonprescription 
pharmacological interventions versus placebo/inactive control vary 
as a function of patient characteristics (i.e., age, sex, race/
ethnicity, depression, pre-treatment cognitive or functional level/
CATD stage, living setting)?
    KQ 3: In adults with CATD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus other active interventions for treatment of 
cognition, function, and quality of life?
    KQ 3a: In adults with CATD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus other prescription pharmacological 
interventions for treatment of cognition, function, and quality of 
life?
    KQ 3b: In adults with CATD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus nonprescription pharmacological interventions 
for treatment of cognition, function, and quality of life?
    KQ 3c: In adults with CATD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus nonpharmacological interventions for treatment 
of cognition, function, and quality of life?
    KQ 3d: In adults with CATD, does the comparative effectiveness 
of prescription pharmacological interventions versus other active 
interventions for treatment of cognition, function, and quality of 
life vary as a function of patient characteristics (i.e., age, sex, 
race/ethnicity, depression, pre-treatment cognitive or functional 
level/CATD stage, living setting)?
    KQ 4: In adults with CATD and behavioral and psychological 
symptoms of dementia (BPSD), what are the efficacy and harms of 
prescription pharmacological interventions versus placebo/inactive 
control for treatment of BPSD?
    KQ 4a: In adults with CATD and BPSD, what are the efficacy and 
harms of prescription pharmacological interventions versus placebo/
inactive control for reducing frequency and severity of future BPSD?
    KQ 4b: In adults with CATD and BPSD, does the efficacy of 
prescription pharmacological interventions versus placebo/inactive 
control for reducing frequency and severity of future BPSD vary as a 
function of patient characteristics (i.e., age, sex, race/ethnicity, 
depression, pre-treatment cognitive or functional level/CATD stage, 
pre-treatment BPSD severity, living setting)?
    KQ 4c: In adults with CATD and BPSD, what are the efficacy and 
harms of prescription pharmacological interventions versus placebo/
inactive control for acute treatment of BPSD?
    KQ 4d: In adults with CATD and BPSD, does the efficacy of 
prescription pharmacological interventions versus placebo/inactive 
control for acute treatment of BPSD vary as a function of patient 
characteristics (i.e., age, sex, race/ethnicity, depression, pre-
treatment cognitive or functional level/CATD stage, pre-treatment 
BPSD severity, living setting)?
    KQ 5: In adults with CATD and BPSD, what are the efficacy and 
harms of nonprescription pharmacological interventions versus 
placebo/inactive control for treatment of BPSD in adults with CATD 
and BPSD?
    KQ 5a: In adults with CATD and BPSD, what are the efficacy and 
harms of nonprescription pharmacological interventions versus 
placebo/inactive control for reducing frequency and severity of 
future BPSD?
    KQ 5b: In adults with CATD and BPSD, does the efficacy of 
nonprescription pharmacological interventions versus placebo/
inactive control for reducing frequency and severity of future BPSD 
vary as a function of patient characteristics (i.e., age, sex, race/
ethnicity, depression, pre-treatment cognitive or functional level/
CATD stage, pre-treatment BPSD severity, living setting)?
    KQ 5c: In adults with CATD and BPSD, what are the efficacy and 
harms of

[[Page 64839]]

nonprescription pharmacological interventions versus placebo/
inactive control for acute treatment of BPSD?
    KQ 5d: In adults with CATD and BPSD, does the efficacy of 
nonprescription pharmacological interventions versus placebo/
inactive control for acute treatment of BPSD vary as a function of 
patient characteristics (i.e., age, sex, race/ethnicity, depression, 
pre-treatment cognitive or functional level/CATD stage, pre-
treatment BPSD severity, living setting)?
    KQ 6: In adults with CATD and BPSD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus other active interventions for treatment of 
BPSD?
    KQ 6a: In adults with CATD and BPSD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus other prescription pharmacological 
interventions for reducing frequency and severity of future BPSD?
    KQ 6b: In adults with CATD and BPSD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus nonprescription pharmacological interventions 
for reducing frequency and severity of future BPSD?
    KQ 6c: In adults with CATD and BPSD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus nonpharmacological interventions for reducing 
frequency and severity of future BPSD?
    KQ 6d: In adults with CATD and BPSD, does the comparative 
effectiveness of prescription pharmacological interventions versus 
other active interventions for reducing frequency and severity of 
future BPSD vary as a function of patient characteristics (i.e., 
age, sex, race/ethnicity, depression, pre-treatment cognitive or 
functional level/CATD stage, pre-treatment BPSD severity, living 
setting)?
    KQ 6e: In adults with CATD and BPSD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus other prescription pharmacological 
interventions for acute treatment of BPSD?
    KQ 6f: In adults with CATD and BPSD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus nonprescription pharmacological interventions 
for acute treatment of BPSD?
    KQ 6g: In adults with CATD and BPSD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus nonpharmacological interventions for acute 
treatment of BPSD?
    KQ 6h: In adults with CATD and BPSD, does the comparative 
effectiveness of prescription pharmacological interventions versus 
other active interventions for acute treatment of BPSD vary as a 
function of patient characteristics (i.e., age, sex, race/ethnicity, 
depression, pre-treatment cognitive or functional level/CATD stage, 
pre-treatment BPSD severity, living setting)?
    KQ 7: In adults with suspected CATD, what are the accuracy, 
comparative accuracy, and harms of different individual cognitive 
diagnostic tests and their combinations for making the diagnosis of 
CATD as defined by full clinical evaluation and/or 
neuropsychological testing with explicit diagnostic criteria?
    KQ 7a: Do the accuracy and comparative accuracy of cognitive 
tests for making the diagnosis of CATD as defined by full clinical 
evaluation and/or neuropsychological testing with explicit 
diagnostic criteria vary as a function of patient characteristics 
(i.e., age, sex, race/ethnicity, education, pre-testing cognitive or 
functional level CATD stage)?
    KQ 8: In adults with a clinical diagnosis of CATD, what are the 
accuracy, comparative accuracy, and harms of brain imaging, CSF, and 
blood tests for diagnosing pathologically confirmed Alzheimer's 
disease as the underlying etiology?
    KQ 8a: Do the accuracy and comparative accuracy of brain 
imaging, CSF, and blood tests for pathologically confirmed 
Alzheimer's disease as the underlying etiology of CATD vary as a 
function of patient characteristics (i.e., age, sex, race/ethnicity, 
depression, education, pre-testing cognitive or functional level 
CATD stage)?

[[Page 64840]]



                                                                     Table 1--PICOTS
                                   [Populations, interventions, comparators, outcomes, timing, settings/study design]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                       Treatment
                                                                     comparator or
              KQ                  Population       Intervention       diagnostic      Health outcomes       Timing          Setting        Study design
                                                                       reference          & harms
                                                                       standard
--------------------------------------------------------------------------------------------------------------------------------------------------------
KQ 1-3: Drug treatment         Adults with CATD  Prescription      For efficacy      Efficacy and      >=24 weeks.....  Cognitive        Efficacy and
 efficacy, comparative          >=50 years of     pharmacologic     comparisons:      comparative                        outcomes:        comparative
 effectiveness & harms on       age.              (drug)            Placebo, Other    effectiveness:                     Community-       effectiveness:
 cognition, function &         Patient            treatment:        inactive          Change in                          dwelling,        RCT, CCT,
 quality of life.               characteristics   Cholinesterase    control.          patient                            Assisted         systematic
                                to be assessed    inhibitors,      For comparative    cognition                          living.          review of RCTs
                                as possible       NMDA              effectiveness     (global screen,                   Functional &      or CCTs.
                                treatment         antagonists.      comparisons:      multidomain,                       QOL outcomes:   Harms: RCT,
                                effect           Nonprescription    Prescription      memory,                            Community-       CCT,
                                modifiers: Age,   pharmacologic     drug treatment,   executive                          dwelling,        controlled
                                Sex, Race/        (drug)            Nonprescription   function,                          Assisted         prospective
                                ethnicity,        treatment: OTC    drug treatment,   language,                          living,          cohort studies
                                Depression, Pre-  supplements,      Nondrug           attention),                        Nursing home.    with >=1,000
                                treatment         Vitamins,         treatment.        function, or                                        participants,
                                cognitive or      Herbals.                            QOL on                                              systematic
                                functional                                            validated test.                                     review of any
                                level/CATD                                           Change in                                            of these study
                                stage, Living                                         disease stage                                       designs.
                                setting.                                              based on
                                                                                      validated test.
                                                                                     Change in
                                                                                      patient ``at
                                                                                      home'' IADL or
                                                                                      ADL function.
                                                                                     Change in
                                                                                      patient
                                                                                      residence to
                                                                                      different level
                                                                                      of independence.
                                                                                     Harms:
                                                                                     General: FDA
                                                                                      defined SAEs,
                                                                                      Withdrawals due
                                                                                      to AEs.
                                                                                     Psychiatric:
                                                                                      Somnolence,
                                                                                      Confusion/
                                                                                      Delirium.
                                                                                     Nonpsychiatric:
                                                                                      Falls,
                                                                                      Extrapyramidal
                                                                                      symptoms,
                                                                                      Stroke.
                                                                                     Mortality (all-
                                                                                      cause, CVD, non-
                                                                                      CVD).
KQ 4-6: Drug treatment         Adults with CATD  Prescription      Efficacy          Efficacy and      Agitation,       Community-       Efficacy and
 efficacy, comparative          >=50 years of     pharmacologic     comparisons:      comparative       aggression,      dwelling,        comparative
 effectiveness & harms on       age with BPSD     treatment:        Placebo, Other    effectiveness:    psychosis or     Assisted         effectiveness:
 BPSD.                          (studies          Cholinesterase    inactive         Primary: Change    Disinhibited     living,          RCT, CCT,
                                specified BPSD    inhibitors,       control.          in the            sexual           Nursing home.    systematic
                                inclusion         NMDA             Comparative        frequency and/    behavior                          review of RCTs
                                criterion).       antagonists,      effectiveness     or severity of    outcomes: >=2                     or CCTs.
                               Patient            Antipsychotics,   comparisons:      patient BPSD*     weeks.                           Harms: RCT,
                                characteristics   second            Prescription      on validated     Depression or                      CCT,
                                to be assessed    generation        drug treatment,   tests,            anxiety                           controlled
                                as possible       (any) and first   Nonprescription   Agitation/        outcomes: >=24                    prospective
                                treatment         generation        drug treatment,   aggression,       weeks.                            cohort studies
                                effect            (only             Nondrug           Psychosis,                                          >=1,000
                                modifiers: Age,   haloperidol),     treatment.        Depression,                                         participants,
                                Sex, Race/        Antidepressants                     Anxiety,                                            systematic
                                ethnicity, Pre-   , Anti-seizure/                     Disinhibited                                        review of any
                                treatment         mood                                sexual                                              of these study
                                cognitive or      stabilizers,                        behavior,                                           designs.
                                functional        Anxiolytics,                        Change in
                                level/CATD        benzodiazepine,                     patient QoL on
                                stage, Pre-       Anxiolytics,                        validated test,
                                treatment BPSD    other Hormonal                      Change in
                                severity,         agents                              validated
                                Living setting.   (Disinhibited                       general
                                                  sexual behavior                     behavior scale.
                                                  only),                             Secondary:
                                                  Cannabinoids,                       Change in
                                                  Combinations.                       caregiver/staff
                                                 Nonprescription                      outcomes on
                                                  pharmacologic                       validated
                                                  treatment: OTC                      tests,
                                                  supplements,                        Depression,
                                                  Vitamins,                           Global stress/
                                                  Herbals.                            distress, QOL,
                                                                                      Burden.
                                                                                     Harms:..........
                                                                                     General: FDA
                                                                                      defined
                                                                                      composite SAE
                                                                                      outcome,
                                                                                      Withdrawals due
                                                                                      to AE.
                                                                                     Psychiatric:
                                                                                      Somnolence,
                                                                                      Confusion/
                                                                                      Delirium.
                                                                                     Nonpsychiatric:
                                                                                      Falls,
                                                                                      Extrapyramidal
                                                                                      symptoms,
                                                                                      Stroke,
                                                                                      Mortality (all-
                                                                                      cause, CVD, non-
                                                                                      CVD).

[[Page 64841]]

 
KQ 7-8: Diagnostic test        Cognitive tests:  Brief, validated  Cognitive tests:  Accuracy and      Any............  Community-       Accuracy and
 accuracy & harms (also see     Adults >=50       cognitive         Full clinical     comparative                        dwelling,        comparative
 Table 2 below).                years of age      tests: Global     evaluation and/   accuracy (e.g.,                    Assisted         accuracy:
                                with suspected    (brief screens,   or                TP, FP, TN, FN,                    living.          Controlled
                                CATD.             multi-domain      neuropsychologi   sensitivity,                                        observational
                               Biomarker tests    batteries),       cal testing       specificity,                                        studies (i.e.,
                                only: Adults      Single domain     with explicit     PPV, NPV).                                          cross-
                                >=50 years of     tests (memory,    diagnostic       Of cognitive                                         sectional,
                                age with          executive,        criteria.         tests for                                           retrospective
                                clinical          language,        Biomarker tests:   confirming                                          cohort, case
                                syndrome of       attention.        Postmortem        clinical                                            control);
                                CATD.            Biomarker tests:   neuropathologic   syndrome of                                         systematic
                               Patient           Brain imaging:     al confirmation   CATD.                                               review of
                                characteristics   CT/MRI: Medial    of AD.           Of biomarker                                         controlled
                                to be assessed    temporal                            tests for                                           observational
                                as possible       atrophy/                            confirming that                                     studies.
                                effect            hippocampal                         etiology of                                        Harms:
                                modifiers of      volume,                             CATD is AD.                                        Controlled
                                diagnostic test   Cortical                           Harms:..........                                     observational
                                accuracy: Age,    thickness, DTI                     Psychological or                                     studies (i.e.,
                                Sex, Race/        indices.                            behavioral.                                         cross-
                                ethnicity,       PET: \18\F-FDG                      True positive:                                       sectional,
                                Education,        PET, Amyloid                        Labeling stigma.                                    retrospective
                                Depression.       PET, \11\C-PiB                     False positive:                                      cohort, case
                               Pre-test           and fluorinated                     Incorrect                                           control,
                                cognitive or      tracers (e.g.                       diagnosis,                                          prospective
                                functional        florbetapir,                        Labeling                                            cohort);
                                level/CATD        flutemetamol,                       stigma, Side                                        systematic
                                stage.            florbetaben),                       effects of                                          review of
                                                  Tau PET.                            unneeded                                            controlled
                                                 fMRI: Resting                        interventions                                       observational
                                                  state and task                      (e.g.,                                              studies.
                                                  specific                            restrictions on
                                                  activation.                         independence).
                                                 SPECT: Resting                      False negative:
                                                  state cerebral                      Unexplained
                                                  perfusion.                          symptoms,
                                                 CSF tests:                           Failure to make
                                                  A[beta]42,                          appropriate
                                                  A[beta]42/                          interventions
                                                  A[beta]40                           (e.g., safety
                                                  ratio, t-tau, p-                    precautions,
                                                  tau, t-tau/                         future
                                                  A[beta]42                           planning).
                                                  ratio, p-tau/                      Any test result:
                                                  A[beta]42                           Patient or
                                                  ratio,                              caregiver
                                                  neurofilament                       mental distress.
                                                  light protein.                     Physical:
                                                 Blood tests:                         Directly from
                                                  A[beta]42,                          diagnostic
                                                  A[beta]42/                          tests: Pain,
                                                  A[beta]40                           Infection,
                                                  ratio, APP.                         Headache,
                                                 Combinations....                     Radiation.
--------------------------------------------------------------------------------------------------------------------------------------------------------
* For this report, two psychological symptoms that are components of BPSD have been excluded due to their coverage in recent, high quality systematic
  reviews--apathy and sleep disturbances.18 19 In addition, wandering was also eliminated, as this symptom is usually treated with nonpharmacologic
  interventions, which are not covered as interventions in this review.
[dagger] Strength of evidence (SOE) will be evaluated for the 1-2 most commonly reported validated treatment efficacy outcomes for each of the following
  test categories: disease stage, global cognitive screening tests, global multidomain cognitive tests, memory, executive functioning, language,
  attention, function, quality of life, BPSD agitation/aggression, and the harms outcome of serious adverse events. Additional treatment outcomes will
  be considered for SOE grading when available data allow. For diagnostic tests, SOE will be graded for the 1-2 most commonly reported validated tests
  for each of the following categories: global cognitive screening tests, global multidomain cognitive tests, memory, MRI, PET, and CSF tests.
  Additional diagnostic testing outcomes will be considered for SOE grading when available data allow.
A[szlig] = beta amyloid, AD = Alzheimer's dementia, ADL = activities of daily living, AE = adverse events, APOE = apolipoprotein E, APP = amyloid
  precursor protein, BPSD = behavioral and psychological symptoms of dementia, CATD = clinical Alzheimer's-type dementia, CCT = controlled clinical
  trial, CSF = cerebrospinal fluid, CT = computed tomography, CVD = cardiovascular disease, DTI = diffusion tensor imaging, FDG = fluorodeoxyglucose,
  fMRI = functional magnetic resonance imaging, FN = false negative, FP = false positive, IADL = instrumental activities of daily living, MCI = mild
  cognitive impairment, MRI = magnetic resonance imaging, NMDA = N-methyl-D-aspartate, NPV = negative predictive value, OTC = over-the-counter, PET =
  positron emission tomography, PPV = positive predictive value, p-tau = abnormally phosphorylated tau, QOL = quality of life, RCT = randomized clinical
  trial, ROC = receiver operating characteristic, SAE = serious adverse events, SPECT = single-photon emission computed tomography, TN = true negative,
  TP = true positive, t-tau = total tau.


[[Page 64842]]


    Table 2--Prescription Drugs Used for Treatment of CATD Cognition,
                    Function, Quality of Life or BPSD
------------------------------------------------------------------------
             Class of drug                         Drug name(s)
------------------------------------------------------------------------
Cholinesterase inhibitor...............  Donepezil *, rivastigmine *,
                                          galantamine *.
NMDA receptor antagonist...............  Memantine *.
Cholinesterase inhibitor/NMDA receptor   Donepezil/Memantine *.
 antagonist combination.
1st generation (typical) antipsychotic.  only Haloperidol.
2nd generation (atypical) antipsychotic  e.g., Risperidone, quetiapine,
                                          olanzapine, aripiprazole,
                                          clozapine.
Anti-depressant, selective serotonin-    e.g., Citalopram, escitalopram,
 reuptake inhibitor (SSRI).               sertraline, fluoxetine,
                                          fluvoxamine, paroxetine.
Anti-depressant, serotonin-              e.g., Duloxetine, venlafaxine.
 norepinephrine reuptake inhibitor
 (SNRI).
Anti-depressant, other [dagger]........  e.g., Trazodone, bupropion,
                                          mirtazapine.
Anti-seizure/mood stabilizer...........  e.g., Valproate, gabapentin,
                                          carbamazepine, lamotrigine.
Anti-anxiety, benzodiazepine...........  e.g., Clonazepam, diazepam,
                                          lorazepam, temazepam,
                                          alprazolam.
Anti-anxiety, other....................  Buspirone.
Mixed..................................  Dextromethorpan/Quinidine.
Hormones (antiandrogens, estrogens,      e.g., medroxyprogesterone
 gonadotropin-releasing hormone           acetate, cyproterone acetate,
 analogues).                              leuprolide.
Cannabinoids...........................  e.g., medical marijuana.
------------------------------------------------------------------------
* US FDA approved indication for Alzheimer's dementia.
[dagger] Excludes MAO-inhibitor, tricyclic and tetracyclic
  antidepressants.
BPSD = behavioral and psychological symptoms of dementia, CATD =
  clinical Alzheimer's-type dementia, NMDA = N-methyl-D-aspartate, SSRI
  = selective serotonin reuptake inhibitor, SNRI = selective
  norepinephrine reuptake inhibitor.

References

1. Plassman BL, Langa KM, Fisher GG, et al. Prevalence of dementia 
in the United States: the aging, demographics, and memory study. 
Neuroepidemiology. 2007;29(1-2):125-32. doi: 10.1159/000109998. 
PMID: 17975326.
2. Langa KM, Larson EB, Crimmins EM, et al. A Comparison of the 
Prevalence of Dementia in the United States in 2000 and 2012. JAMA 
Intern Med. 2017 Jan 01;177(1):51-8. doi: 10.1001/
jamainternmed.2016.6807. PMID: 27893041.
3. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of 
dementia due to Alzheimer's disease: recommendations from the 
National Institute on Aging-Alzheimer's Association workgroups on 
diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 
2011 May;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. PMID: 
21514250.
4. Hurd MD, Martorell P, Delavande A, et al. Monetary costs of 
dementia in the United States. N Engl J Med. 2013 Apr 
4;368(14):1326-34. doi: 10.1056/NEJMsa1204629. PMID: 23550670.
5. Zhao QF, Tan L, Wang HF, et al. The prevalence of 
neuropsychiatric symptoms in Alzheimer's disease: Systematic review 
and meta-analysis. J Affect Disord. 2016 Jan 15;190:264-71. doi: 
10.1016/j.jad.2015.09.069. PMID: 26540080.
6. What is Alzheimer's? Alzheimer's Association. www.alz.org/alzheimers-dementia/what-is-alzheimers. Accessed on November 2, 
2018.
7. Alzheimer's Disease. Centers for Disease Control and Prevention. 
www.cdc.gov/aging/aginginfo/alzheimers.htm. Accessed on November 2, 
2018.
8. Association AP. Diagnostic and Statistical Manual of Mental 
Disorders, Third Edition, Revised (DSM-IIIR); 1987.
9. 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 Human Services Task Force on 
Alzheimer's Disease. Neurology. 1984 Jul;34(7):939-44. PMID: 
6610841.
10. Association AP. Diagnostic and Statistical Manual of Mental 
Disorders: DSM-5; 2013.
11. Cure S, Abrams K, Belger M, et al. Systematic literature review 
and meta-analysis of diagnostic test accuracy in Alzheimer's disease 
and other dementia using autopsy as standard of truth. J Alzheimers 
Dis. 2014;42(1):169-82. doi: 10.3233/JAD-131559. PMID: 24840572.
12. Frisoni GB, Boccardi M, Barkhof F, et al. Strategic roadmap for 
an early diagnosis of Alzheimer's disease based on biomarkers. 
Lancet Neurol. 2017 Aug;16(8):661-76. doi: 10.1016/S1474-
4422(17)30159-X. PMID: 28721928.
13. Kane RLB, M.; Fink, H.A.; Brasure, M.; Davila, H.; Desai, P.; 
Jutkowitz, E.; McCreedy, E.; Nelson, V.A.; McCarten, J.R.; Calvert, 
C.; Ratner, E.; Hemmy, L.S.; Barclay, T. Interventions To Prevent 
Age-Related Cognitive Decline, Mild Cognitive Impairment, and 
Clinical Alzheimer's-Type Dementia. AHRQ Publication No. 17-EHC008-
EF. Rockville, MD: Quality AfHRa; February 2017 2017. 
www.effectivehealthcare.ahrq.gov/reports/final.cfm
14. Reus VI, Fochtmann LJ, Eyler AE, et al. The American Psychiatric 
Association Practice Guideline on the Use of Antipsychotics to Treat 
Agitation or Psychosis in Patients With Dementia. Am J Psychiatry. 
2016 May 1;173(5):543-6. doi: 10.1176/appi.ajp.2015.173501. PMID: 
27133416.
15. Brasure M, Jutkowitz E, Fuchs E, et al. Nonpharmacologic 
Interventions for Agitation and Aggression in Dementia. Rockville 
(MD); 2016.
16. Qaseem A, Snow V, Cross JT, Jr., et al. Current pharmacologic 
treatment of dementia: a clinical practice guideline from the 
American College of Physicians and the American Academy of Family 
Physicians. Ann Intern Med. 2008 Mar 4;148(5):370-8. PMID: 18316755.
17. Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of 
behavioral and psychological symptoms of dementia. BMJ. 2015 Mar 
2;350:h369. doi: 10.1136/bmj.h369. PMID: 25731881.
18. Ruthirakuhan MT, Herrmann N, Abraham EH, et al. Pharmacological 
interventions for apathy in Alzheimer's disease. Cochrane Database 
Syst Rev. 2018 May 4;5:CD012197. doi: 10.1002/
14651858.CD012197.pub2. PMID: 29727467.
19. McCleery J, Cohen DA, Sharpley AL. Pharmacotherapies for sleep 
disturbances in dementia. Cochrane Database Syst Rev. 2016 Nov 
16;11:CD009178. doi: 10.1002/14651858.CD009178.pub3. PMID: 27851868.
20. Hackshaw A. Small studies: strengths and limitations. Eur Respir 
J. 2008 Nov;32(5):1141-3. doi: 10.1183/09031936.00136408. PMID: 
18978131.
21. Viswanathan M, Ansari M, Berkman N, et al. Assessing the Risk of 
Bias of Individual Studies in Systematic Reviews of Health Care 
Interventions AHRQ. 2012.
22. Methods Guide for Medical Test Reviews. AHRQ Publication No. 12-
EC017. Rockville, MD: Quality AfHRa; June 2012. 
www.effectivehealthcare.ahrq.gov/reports/final.cfm.
23. Whiting PF, Rutjes AW, Westwood ME, et al. QUADAS-2: a revised 
tool for the quality assessment of diagnostic accuracy studies. Ann 
Intern Med. 2011 Oct 18;155(8):529-36. doi: 10.7326/0003-4819-155-8-
201110180-00009. PMID: 22007046.
24. Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical 
appraisal tool for systematic reviews that include randomised or 
non-randomised studies of healthcare interventions, or both. BMJ. 
2017 Sep 21;358:j4008. doi: 10.1136/bmj.j4008. PMID: 28935701.

[[Page 64843]]

25. Fu R, Gartlehner G, Grant M, et al. Conducting quantitative 
synthesis when comparing medical interventions: AHRQ and the 
Effective Health Care Program. J Clin Epidemiol. 2011 
Nov;64(11):1187-97. doi: 10.1016/j.jclinepi.2010.08.010. PMID: 
21477993.
26. Takwoingi Y. Meta-analysis of test accuracy studies in Stata: a 
bivariate model approach. Version 1.1.
27. Owens DK, Lohr KN, Atkins D, et al. AHRQ series paper 5: grading 
the strength of a body of evidence when comparing medical 
interventions--agency for healthcare research and quality and the 
effective health-care program. J Clin Epidemiol. 2010 May;63(5):513-
23. doi: S0895-4356(09)00093-6 [pii] 10.1016/j.jclinepi.2009.03.009. 
PMID: 19595577.
28. Singh S, Chang SM, Matchar DB, et al. Chapter 7: grading a body 
of evidence on diagnostic tests. J Gen Intern Med. 2012 Jun;27 Suppl 
1:S47-55. doi: 10.1007/s11606-012-2021-9. PMID: 22648675.
29. Berkman ND, Lohr KN, Ansari M, et al. Grading the Strength of a 
Body of Evidence When Assessing Health Care Interventions for the 
Effective Health Care Program of the Agency for Healthcare Research 
and Quality: An Update. Methods Guide for Effectiveness and 
Comparative Effectiveness Reviews. Rockville (MD); 2008.
30. Atkins D, Chang S, Gartlehner G, et al. Assessing the 
Applicability of Studies When Comparing Medical Interventions. 
Methods Guide for Effectiveness and Comparative Effectiveness 
Reviews. Rockville (MD); 2008.

Francis D. Chesley, Jr.,
Acting Deputy Director.
[FR Doc. 2018-27361 Filed 12-17-18; 8:45 am]
 BILLING CODE 4160-90-P