Clinical Excellence Test Review Toolkit

Prepared on : 25th May 2021

Updated on : 21 February 2024
 CONTENT

Topic Page

Introduction 2-3

Disease Matrix - 1 (AD) 4-7

Disease Matrix - 1 (PD) 7 - 10

Disease Matrix - 1 (MS) 10 - 12

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 INTRODUCTION

Objective

● To understand the process of reviewing and matching the suitable patients for a clinical
trial.
● To understand the symptoms and the process of diagnosing relevant diseases that
SiteRx is involved with.
● To provide the necessary information to make a decision in regards to a patient’s
eligibility to be referred to participate in a clinical drug trial.

Clinical research is a systematic process that is required to assess the safety and efficacy
of a compound to receive FDA approval to use for any stated indication in the US. Clinical
trials in the US are governed by the FDA to ensure the rights and welfare of volunteers are
protected. The FDA inspects all sites that conduct clinical trials in the US.

Clinical trials can be funded by the government, industry (Pharmaceuticals), and private
parties. Clinical trials involve research in drugs and medical devices. The procedures
written for a particular trial are called a protocol and must be reviewed and approved by
Institutional Review Boards (IRBs). These boards are composed of at least 5 members that
include scientists, doctors, and lay people. They review and approve clinical trials taking
place within their jurisdiction before the trials can begin. The purpose of the IRB is to
ensure that appropriate steps are taken to protect the rights and welfare of the participants
as subjects of research.

Many neurodegenerative diseases such as Alzheimer’s Disease, are clinical diagnosis,

meaning there is no definitive test to make the diagnosis with certainty. As research
continues, there is more understanding of these diseases and there have been discoveries
of the different disease states. For this reason, it is important to know the symptoms and
clinical history (the symptoms over time) to accurately diagnose a patient with a
neurodegenerative disease. Information for the relevant diseases is provided in this manual

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so the reviewer is well informed of cases that may or may not be consistent with the
diagnosis.

Overview Guides have been created from the Sponsor protocol in order to provide the
reviewer with the relevant information in order to make a decision if the patient is or is not a
candidate for a particular clinical trial.

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 Patient Chart Review Matrix

Alzheimer's Disease

Step 1: Basic Exclusionary eligibility

Relevance of patient file Records older than 12 months

Age < 50 OR >90
BMI <=16 and >= 50
Test/lab scores (if present) *Do not exclude MMSE <3
automatically if a score is not present
Patient currently undergoing any other clinical trial that provides
Participation in other trials treatment is exclusionary

Step 2: Determine diagnosis

Number of ICD codes in "Matched" patient file Any one of the given ICDs
1. Locate ICD Codes/Diagnosis Codes Vascular Dementia (F01) = F01.5 (# .50, .51, .511, .518, .52, .53, .54),
F01.A (# .A0, .A11, .A18, .A2, .A3, .A4), F01.B (# .B0, .B11, .B18, .B2, .B3,
.B4), F01.C (# .C0, .C11, .C18, .C2, .C3, .C4)
Dementia (F02) = F02.8 (# .80, .81, .811, .818, .82, .83, .84) F02.A (# .A0,
.A11, .A18, .A2, .A3) F02.B18, F02.C (# .C0, .C18, .C2) (F03) = F03.9 (#
.90, .91, .92) F03.A ( # .A0, .A18, .A3) F03.B (# .B0, .B18, .B2, .B3, .B4)
F03.C (# .C0, .C11, .C18, .C2, .C3, .C4)
Alzheimer's (G30) = G30.0, G30.1, G30.8, G30.9
Cognitive Impairment (G31) = G31.1, G31.34, G31.84, G31.9
Amnesia, Cognitive Functions, Visuospacial deficit (R41) = R41.0, R41.1,
R41.2, R41.8 (# .82, .841, .842, .89) R41.8 (#.840, .843, .844) *Note:
R41.8 (#.840, .843, .844) Must Include Subjective Cognitive
Impairement
Memory Loss (780) = 780.93

Subjective Cognitive Impairment (No ICD 10 Code)

2. Look for Diagnosis description words or Diagnosis: Alzheimer's, MCI, Vascular Dementia
comorbidities Memory problems, word finding, problems remembering names
Memory Loss Caused Due to Multifactorial/Multifactorial memory loss
or dementia

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3. Locate Inclusionary medications as part of Acetylcholinesterase inhibitors: Donepezil (Aricept),
determining diagnosis Galantamine(Razadyne), Rivastigmine(Exelon),
Donepezil/Memantine(Namzaric)
NMDA receptor antagonist: Memantine(Namenda/Namenda XR).
Amyloid Beta-Directed Antibodies: Lecanemab (Leqembi)

Step 3: Neurological or brain conditions.

Neurological Conditions Creutzfeldt-Jakob disease

Fahr’s Disease
Huntington’s Disease
Intellectual Disability = Autism & Down’s Syndrome
End Stage Dementia
Multiple Sclerosis
Progressive Supranuclear Palsy (PSP)
Imaging and MRI Findings NA

Concussion/Brain injury NA
Stroke NA

Seizure/Epilepsy DNQ if there is clear evidence of 2 or more seizures within 6 months.

Push if diagnosis of seizures OR epilepsy but patient has no evidence
of recent seizures or no timeframe noted.
Miscellaneous Brain/Neurological NA

Step 4: Psychological & behavioural conditions

Psychiatric condition Current diagnosis of Manic Depressive Disorder (historical OK),

Schizophrenia, Schizoaffective Disorder
Psychotic conditions NA

Suicidal Ideation DNQ suicide if 1.) positive CSSRS - suicide screening within 6 months or
2.) evidence of being actively suicidal in recent notes. Push to CE2 if
there is mention of suicide but no timeframe was provided.
Drug/Substance abuse Current ongoing drug abuse (including amphetamines, cocaine, crack
cocaine, heroine, and phencyclidine)
Marijuana is acceptable
Alcohol abuse NA
Cigarette smoking NA

Step 5: Medical conditions

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Malignancy/Cancer Cancer currently being treated with medication.
**Exception = hormonal treatment following treatment for breast
cancer

Cardiac conditions NA
Metabolic/Endocrine NA
Liver conditions History of Liver failure
Cirrhosis
Pulmonary NA
Renal conditions CKD stage 4 and 5
End stage renal disease (ESRD)
Patient on dialysis
Implants Brain Shunt
VP Shunt
Allergy NA
Communicable Diseases HIV
Syphilis
Miscellaneous conditions NA

Step 6: Exclusionary medications

Exclusionary medications Immunosuppressants:

Adalimumab/ humira
Anakinra/ kineret
Azathioprine/ alefacept
Basiliximab
Belimumab
Certolizumab pegol
Cyclosporine/ gengraf/ neoral/ sandimmune
Denosumab/ xgeva
Efalizumab/ raptiva
Etanercept/ enbrel
Evolocumab/ repatha
Infliximab/ remicade
Leflunomide/ arava
Lymphocyte immune globulin
Methotrexate/ rheumatrex/cyclophosphamide/cytoxan,
Muromonab-CD3
Mycophenolate/ mofetil/ cellcept/ myfortic
Omalizumab/xolair
Sirolimus
Tacrolimus/ astagraf/ envarsus/ hecoria, prograf
Voclosporin/ lupkynis

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 Antiviral: Azidothymidine, Lamivudine (Epivir, Epivir HBV)
Immune Globulin IV, IVIG: Carimune, Flebogamma, Gamimune N,
Gammagard, Gamunex, Gammar-P IV, Iveegam, Octagam, Panglobulin,
Vigam, Polygam S/D, Privigen, Sandoglobulin, Venoglobulin-S
Antiepileptic taken for seizures: Carbamazepine (Tegretol, Epitol,
Equetro), divalproex sodium (Depakote), phenytoin (Dilantin),
levetiracetam (Keppra, Elpsia), lamotrigine (Lamictal), oxcarbazepine
(Oxtellar), topiramate (Topamax, Trokendi)
Oncological: camptothecin derivatives, Canertinib, Diflomotecan,
Flavopiridol, gefitinib (Iressa), imatinib mesylate (Gleevec),
Indolocarbazole, Irinotecan (Camptosar), Lapatinib (Tykerb),
Mitoxantrone (Novantrone), Nilotinib (Tasigna), Topotecan (Hycamtin)

Parkinson Disease

Step 1: Basic Exclusionary eligibility

Relevance of patient file Records older than 12 months

Age <30 OR >85
BMI NA
MoCA <11 or >30
MMSE <15 or >30
SLUMS <13 or >30
NA
Test/lab scores (if present) *Do not exclude
automatically if a score is not present NA
Patient currently undergoing any other clinical trial that provides
Participation in other trials treatment is exclusionary

Step 2: Determine diagnosis

Number of ICD codes in "Matched" patient file Any one of the given ICD codes unless otherwise noted.

1. Locate ICD Codes/Diagnosis Codes Parkinson's (G20) = G20 (#.A, .A1, .A2, .B, .B1, .B2, .C)
Dementia (FO2.81) = F02.81 *Note: Must also include hallucinations

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 Mental Disorder (FO9) = F09 *Note: Must also include G20
Dementia (G31) = G31.83 (with Lewy Bodies or with Parkinson's);
G31.84 (Note: G31.84 Must also include G20)
Amnesia/Disorientation (R41) = R41.0, R41.1, R41.2, R41.3 *Note:
Must also have G20
Hallucinations (R44; F44) = R44.3, F44.1 *NOTE: Only can be
considered if G20 is also mentioned.
2. Look for Diagnosis description words or Diagnosis: Parkinson Disease, Parkinsonian Disorders, Basal Ganglia
comorbidities Diseases, Movement Disorders, Synucleinopathies, Brain disease,
CNS disease, Neurodegenerative disease, Nervous system disease
Behaviors: Bradykinesia/ slowness, Tremor/ Resting Tremor, Rigidity/
Stiffness, Shuffled gait, Postural Instability, Falls
Findings: MRI Brain, DaT scan, LRRK, LKRR2, Hoehn and Yahr Stages
1-3
Treatments: DBS
3. Locate Inclusionary medications as part of Parkinson's Medications
determining diagnosis Amantadine (Gocovri, Symmetrel, Osmolex)
Carbidopa/levodopa (Sinemet, Rytary) > oral
Carbidopa/levodopa/entacapone (Stalevo)
Levodopa Inhalation Powder (Inbrija)
Sinement CR (Levadopa, extended release)
Entacapone (Comtan)
Pramipexole (Mirapex)
Rotigotine (Neupro Patch)
Apomorphine (Apokyn, Kynmobi)
Rasagiline (Azilect)
Ropinirole (Requip)
Safinamide (Xadago)
Selegiline
Pimavanserin (Nuplazid)
Quetiapine (Seroquel)

Step 3: Neurological or brain conditions

Neurological Conditions Drug induced Parkinsonism

Lewy Body Dementia (DLB)
Metabolic Neurogenetic Disorders (Wilson’s disease)
Multiple Sclerosis
Multiple system atrophy (MSA)
Progressive supranuclear Palsy (PSP)
Vascular Parkinsonism and other Secondary Parkinsonism

Imaging and MRI Findings NA

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Concussion/Brain injury NA
Stroke Stroke/Transient Ischemic Attack(TIA)/Cerebral Vascular Accident
(CVA) within 1 year and persistent symptoms (i.e visual loss,
language impairment, sudden onset of cognitive impairment)
If time frame not mentioned, push through
Seizure/Epilepsy NA
Miscellaneous Brain/Neurological History of brain surgery for PD (e.g. pallidotomy, fetal tissue
transplant)
History of focused ultrasound treatment (deep brain stimulations are
allowed)

Step 4: Psychological & behavioural conditions

Psychiatric condition Schizophrenia

Psychotic conditions NA
Suicidal Ideation Subjects with current suicidal ideation. NOTE: If the chart is greater
than six months old, approve for further conversation with the patient.
Suicidal attempt within lifetime
Drug/Substance abuse Drug abuse (including amphetamines, cocaine, crack cocaine,
heroine, and phencyclidine) within five years
Marijuana is acceptable
Alcohol abuse Alcoholism in the last 5 years - Etoh / Alcohol abuse / Alcohol use
disorder / Alcohol dependence
Cigarette smoking NA

Step 5: Medical conditions

Malignancy/Cancer NA

Cardiac conditions Myocardial infarction within 1 year

Unstable angina
Congestive heart failure (CHF) 3 or 4 within 1 year
Metabolic/Endocrine A1C ≥ 8%
Liver conditions NA

Pulmonary Severe Emphysema/Severe Bronchitis/severe Asthma or Pulmonary

disease requiring oxygen
Renal conditions CKD stage 4 and 5
End stage renal disease (ESRD)
Patient on dialysis

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Implants Brain Shunt
VP Shunt
Contraindications to MRI
Allergy NA
Communicable Diseases HIV
Syphilis
Miscellaneous conditions NA

Step 6: Exclusionary medications

Exclusionary medications Amphetamine (Adzenys, Dyanavel, Evekeo)

Multiple Sclerosis

Step 1: Basic Exclusionary eligibility

Relevance of patient file Records older than 12 months

Age <18 OR >55
BMI NA
Test/lab scores (if present) *Do not exclude NA
automatically if a score is not present
Patient currently undergoing any other clinical trial that provides
Participation in other trials treatment is exclusionary

Step 2: Determine diagnosis

Number of ICD codes in "Matched" patient file Any one of the given ICD codes

1. Locate ICD Codes/Diagnosis Codes Multiple Sclerosis (G35) = G35, G35.1, G35.2, G35.10, G35.11
Cerebral Ataxia (G32) = G32.81
Neuromyelitis Optica (G36) = G36.0, G36.9
Diffuse sclerosis of central nervous system (G37) = G37.0, G37.1,

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 G37.5, G37.9
2. Look for Diagnosis description words or comorbidities Diagnosis: Relapsing Multiple Sclerosis (RMS), Clinically Isolated
Syndrome (CIS), Relapsing Remitting MS (RRMS), and Secondary
Progressive MS (SPMS), EDSS
Treatments: Disease modifying therapy (DMT)
Note: Patients with a diagnosis of “Multiple Sclerosis” without the
type mentioned can be pushed through for further evaluation
3. Locate Inclusionary medications as part of NA
determining diagnosis

Step 3: Neurological or brain conditions

Neurological Conditions Primary Progressive MS (PPMS)

Imaging and MRI Findings NA

Concussion/Brain injury NA
Stroke NA
Seizure/Epilepsy NA
Miscellaneous Brain/Neurological NA

Step 4: Psychological & behavioural conditions

Psychiatric condition NA
Psychotic conditions NA
Suicidal Ideation Subjects with current suicidal ideation. NOTE: If chart is greater than
six months old, approve for further conversation with patient.
Drug/Substance abuse Current ongoing drug abuse (including amphetamines, cocaine,
crack cocaine, heroine, and phencyclidine)
Alcohol abuse Alcoholism in the last 6 months - Etoh / Alcohol abuse / Alcohol use
disorder / Alcohol dependence
Cigarette smoking NA

Step 5: Medical conditions

Malignancy/Cancer Cancer currently being treated with medication.

**Exception = hormonal treatment following treatment for breast
cancer

Cardiac conditions Class III and IV Congestive Heart Failure (CHF)

Metabolic/Endocrine NA
Liver conditions History of Liver failure
Cirrhosis

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Pulmonary Severe Chronic Obstructive Pulmonary Failure (COPD)
Renal conditions Chronic kidney disease (CKD) stage 4 or 5
End Stage Renal Disease (ESRD).
Glomerular Filtration Rate (GFR) < 30
Implants NA
Allergy NA
Communicable Diseases HIV
Syphilis
Miscellaneous conditions Pregnant or breastfeeding females

Step 6: Exclusionary medications

Exclusionary medications Multiple Sclerosis Treatments:

Lymphoid irradiation, bone marrow transplantation
Cyclophosphamide
Mitoxantrone
Ocrevus (If more than 5 infusions received)

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