Federal Register / Vol. 83, No. 242 / Tuesday, December 18, 2018 / Notices 64837 

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. 

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

Form name Number of 

respondents 

Number of 

responses per 

respondent 

Hours per 

response 

Total burden 

hours 

HCUP Application Form .................................................................. 1,500 1 .............................. 10/60 ..................... 250 

HCUP DUA Training ....................................................................... 1,500 1 .............................. 15/60 ..................... 375 

HCUP DUA ..................................................................................... 1,500 1 .............................. 5/60 ....................... 125 

Total ......................................................................................... 4,500 na ............................ na .......................... 750 

EXHIBIT 2—ESTIMATED ANNUALIZED COST BURDEN

Form name Number of 

respondents 

Total 

burden hours 

Average hourly 

wage rate * 

Total cost 

burden 

HCUP Application Form ....................................................................... 1,500 250 ....................... $39.55 ................. $9,887 

HCUP DUA Training ............................................................................ 1,500 375 ....................... 39.55 ................... 14,831 

HCUP DUA .......................................................................................... 1,500 125 ....................... 39.55 ................... 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. 

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 

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: 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. 


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64838 Federal Register / Vol. 83, No. 242 / Tuesday, December 18, 2018 / 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. 

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 

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 


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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, 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 

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)? 


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TABLE 1—PICOTS 

[Populations, interventions, comparators, outcomes, timing, settings/study design] 

KQ Population Intervention 

Treatment comparator 

or diagnostic reference 

standard 

Health outcomes & harms Timing Setting Study design 

KQ 1–3: Drug treatment 

efficacy, comparative effectiveness & harms on cognition, function & quality of life.

Adults with CATD ≥50 years of agePatient characteristics to be assessed as possible treatment effect modifiers: Age, Sex, Race/ 

ethnicity, Depression, Pre-treatment cognitive or functional level/ CATD stage, Living setting.

Prescription pharmacologic (drug) 

treatment: Cholinesterase inhibitors, NMDA antagonists.

Nonprescription pharmacologic 

(drug) treatment: OTC supplements, Vitamins, Herbals.

For efficacy comparisons: Placebo, Other 

inactive control.

For comparative effectiveness comparisons: 

Prescription drug treatment, Nonprescription drug treatment, Nondrug treatment.

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.

≥24 weeks ..................... Cognitive outcomes: 

Community-dwelling, Assisted living.

Functional & QOL outcomes: Communitydwelling, Assisted living, Nursing home.

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. 

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 

efficacy, comparative effectiveness & harms on BPSD.

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.

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.

Efficacy comparisons: 

Placebo, Other inactive control.

Comparative effectiveness comparisons: 

Prescription drug treatment, Nonprescription drug treatment, Nondrug treatment.

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.

Agitation, aggression, 

psychosis or Disinhibited sexual behavior outcomes: ≥2 weeks.

Depression or anxiety 

outcomes: ≥24 weeks.

Community-dwelling, 

Assisted living, Nursing home.

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. 

Psychiatric: Somnolence, Confusion/ 

Delirium. 

Nonpsychiatric: Falls, Extrapyramidal 

symptoms, Stroke, Mortality (allcause, CVD, non-CVD).


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KQ 7–8: Diagnostic test 

accuracy & harms (also see Table 2 below).

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. 


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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 antagonist combination ............ Donepezil/Memantine *. 

1st generation (typical) antipsychotic ....................................................... only Haloperidol. 

2nd generation (atypical) antipsychotic .................................................... e.g., Risperidone, quetiapine, olanzapine, aripiprazole, clozapine. 

Anti-depressant, selective serotonin-reuptake inhibitor (SSRI) ............... e.g., Citalopram, escitalopram, sertraline, fluoxetine, fluvoxamine, 

paroxetine. 

Anti-depressant, serotonin-norepinephrine reuptake inhibitor (SNRI) ..... e.g., Duloxetine, venlafaxine. 

Anti-depressant, other † ............................................................................ 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, gonadotropin-releasing hormone 

analogues).

e.g., medroxyprogesterone acetate, cyproterone acetate, leuprolide. 

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. 

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 

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 

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. 


amozie on DSK3GDR082PROD with NOTICES
Federal Register / Vol. 83, No. 242 / Tuesday, December 18, 2018 / Notices 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 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Centers for Medicare & Medicaid 

Services 

[Document Identifier CMS–10465] 

Agency Information Collection 

Activities: Proposed Collection; 

Comment Request 

AGENCY: Centers for Medicare & 

Medicaid Services, HHS. 

ACTION: Notice. 

SUMMARY: The Centers for Medicare & 

Medicaid Services (CMS) is announcing 

an opportunity for the public to 

comment on CMS’ intention to collect 

information from the public. Under the 

Paperwork Reduction Act of 1995 (the 

PRA), federal agencies are required to 

publish notice in the Federal Register 

concerning each proposed collection of 

information (including each proposed 

extension or reinstatement of an existing 

collection of information) and to allow 

60 days for public comment on the 

proposed action. Interested persons are 

invited to send comments regarding our 

burden estimates or any other aspect of 

this collection of information, including 

the necessity and utility of the proposed 

information collection for the proper 

performance of the agency’s functions, 

the accuracy of the estimated burden, 

ways to enhance the quality, utility, and 

clarity of the information to be 

collected, and the use of automated 

collection techniques or other forms of 

information technology to minimize the 

information collection burden. 

DATES: Comments must be received by 

February 19, 2019. 

ADDRESSES: When commenting, please 

reference the document identifier or 

OMB control number. To be assured 

consideration, comments and 

recommendations must be submitted in 

any one of the following ways: 

1. Electronically. You may send your 

comments electronically to http://

www.regulations.gov. Follow the 

instructions for ‘‘Comment or 

Submission’’ or ‘‘More Search Options’’ 

to find the information collection 

document(s) that are accepting 

comments. 

2. By regular mail. You may mail 

written comments to the following 

address: 

CMS, Office of Strategic Operations and 

Regulatory Affairs, Division of 

Regulations Development, Attention: 

Document Identifier/OMB Control 

Number _, Room C4–26–05, 7500 

Security Boulevard, Baltimore, 

Maryland 21244–1850. 

To obtain copies of a supporting 

statement and any related forms for the 

proposed collection(s) summarized in 

this notice, you may make your request 

using one of following: 

1. Access CMS’ website address at 

https://www.cms.gov/Regulations-andGuidance/Legislation/ 

PaperworkReductionActof1995/PRAListing.html. 

2. Email your request, including your 

address, phone number, OMB number, 

and CMS document identifier, to 

Paperwork@cms.hhs.gov. 

3. Call the Reports Clearance Office at 

(410) 786–1326. 

FOR FURTHER INFORMATION CONTACT: 

William N. Parham at (410) 786–4669. 

SUPPLEMENTARY INFORMATION: 

Contents 

This notice sets out a summary of the 

use and burden associated with the 

following information collections. More 

detailed information can be found in 

each collection’s supporting statement 

and associated materials (see 

ADDRESSES). 

CMS–10465 Minimum Essential 

Coverage 

Under the PRA (44 U.S.C. 3501– 

3520), federal agencies must obtain 

approval from the Office of Management 

and Budget (OMB) for each collection of 

information they conduct or sponsor. 

The term ‘‘collection of information’’ is 

defined in 44 U.S.C. 3502(3) and 5 CFR 

1320.3(c) and includes agency requests 

or requirements that members of the 

public submit reports, keep records, or 

provide information to a third party. 

Section 3506(c)(2)(A) of the PRA 

requires federal agencies to publish a 

60-day notice in the Federal Register 

concerning each proposed collection of 

information, including each proposed 

extension or reinstatement of an existing 

collection of information, before 

submitting the collection to OMB for 

approval. To comply with this 

requirement, CMS is publishing this 

notice. 

Information Collection 

Type of Information Collection 

Request: Extension of a currently 

approved collection; Title of 

Information Collection: Minimum 

Essential Coverage; Use: The final rule 

titled ‘‘Patient Protection and Affordable 

Care Act; Exchange Functions: 

Eligibility for Exemptions; 

Miscellaneous Minimum Essential 

Coverage Provisions,’’ published July 1, 

2013 (78 FR 39494) designates certain 

types of health coverage as minimum 

essential coverage. Other types of 

coverage, not statutorily designated and 

not designated as minimum essential 

coverage in regulation, may be 

recognized by the Secretary of Health 

and Human Services (HHS) as minimum 

essential coverage if certain substantive 

and procedural requirements are met. 

To be recognized as minimum essential 

coverage, the coverage must offer 

substantially the same consumer 

protections as those enumerated in the 

Title I of Affordable Care Act relating to 

non-grandfathered, individual health 

insurance coverage to ensure consumers 

are receiving adequate coverage. The 

final rule requires sponsors of other 

coverage that seek to have such coverage 

recognized as minimum essential 

coverage to adhere to certain 

procedures. Sponsoring organizations 

must submit to HHS certain information 

about their coverage and an attestation 

that the plan substantially complies 

with the provisions of Title I of the 

Affordable Care Act applicable to nongrandfathered individual health 

insurance coverage. Sponsors must also 

provide notice to enrollees informing 


amozie on DSK3GDR082PROD with NOTICES