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7.5.2 events of clinical interest

Selected non-serious and serious adverse events are also known as Events of Clinical Interest (ECI) and must be reported within 24 hours to the Sponsor and within 2 working days to Merck Global Safety. (Attn: Worldwide Product Safety; FAX 215 993-1220). For the time period beginning when the consent form is signed until treatment, any ECI, or follow up to an ECI, that occurs to any subject must be reported within 24 hours to the Sponsor and within 2 working days to Merck Global Safety if it causes the subject to be excluded from the trial, or is the result of a protocol-specified intervention, including but not limited to washout or discontinuation of usual therapy, diet, placebo treatment or a procedure. For the time period beginning at treatment through 90 days following cessation of treatment, or 30 days following cessation of treatment if the subject initiates new anticancer therapy, whichever is earlier, any ECI, or follow up to an ECI, whether or not related to Merck product, must be reported within 24 hours to the Sponsor and within 24 hours to Merck Global Safety. Events of clinical interest for this trial include:  
1. An overdose of Merck product, as defined in Section 7.3, that is not associated with clinical symptoms or abnormal laboratory results.  
2. An elevated AST or ALT lab value that is greater than or equal to 3X the upper limit of normal and an elevated total bilirubin lab value that is greater than or equal to 2X the upper limit of normal and, at the same time, an alkaline phosphatase lab value that is less than 2X the upper limit of normal, as determined by way of protocol-specified laboratory testing or unscheduled laboratory testing.*
*Note: These criteria are based upon available regulatory guidance documents. The purpose of the criteria is to specify a threshold of abnormal hepatic tests that may require an additional evaluation for an underlying etiology.
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7.6 protocol-specific exceptions to serious

Efficacy endpoints as outlined in this section will not be reported to Merck as described in Section 7.5 Immediate Reporting of Adverse Events to the Sponsor and to Merck, unless there is evidence suggesting a causal relationship between the drug and the event. Any such event will be submitted to the Sponsor within 24 hours and to Merck Global Safety within 2 working days either by electronic or paper media. Specifically, the suspected/actual events covered in this exception include any event that is disease progression of the cancer under study. The Sponsor will monitor aggregated efficacy endpoint events and safety data to ensure the safety of the subjects in the trial. Any suspected endpoint which upon review is not progression of the cancer under study will be forwarded to Merck Global Safety as a SAE within 2 working days of determination that the event is not progression of the cancer under study Hospitalization related to convenience (e.g. transportation issues etc.) will not be considered a SAE.
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7.7 sponsor responsibility for reporting

All Adverse Events will be reported to regulatory authorities, IRB/IECs and investigators in accordance with all applicable global laws and regulations. Please refer to the Manual of Operations for more details on SAE routing procedures.
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table 6 evaluating adverse events

| V4.0                                       | CTCAE                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           | Grade 1   | Mild; asymptomatic or mid symptoms; clinical or diagnostic observations only; intervention not   |
|--------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------|--------------------------------------------------------------------------------------------------|
| Grading                                    | indicated.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      |           |                                                                                                  |
| Grade 2                                    | Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental  ADL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     |           |                                                                                                  |
| Grade 3                                    | Severe or medically significant but not immediately life-threatening; hospitalization or prolongation or  hospitalization indicated; disabling; limiting self-care ADL.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         |           |                                                                                                  |
| Grade 4                                    | Life threatening consequences; urgent intervention indicated.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   |           |                                                                                                  |
| Grade 5                                    | Death related to AE                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             |           |                                                                                                  |
| Seriousness                                | A serious adverse event is any adverse event occurring at any dose or during any use of Merck product that: †Results in death; or †Is life threatening; or places the subject, in the view of the investigator, at immediate risk of death from the event as it occurred  (Note: This does not include an adverse event that, had it occurred in a more severe form, might have caused death.); or †Results in a persistent or significant disability/incapacity (substantial disruption of one's ability to conduct normal life  functions); or †Results in or prolongs an existing inpatient hospitalization (hospitalization is defined as an inpatient admission, regardless of  length of stay, even if the hospitalization is a precautionary measure for continued observation. (Note: Hospitalization for an elective  procedure to treat a pre-existing condition that has not worsened is not a serious adverse event. A pre-existing condition is a clinical  condition that is diagnosed prior to the use of a Merck product and is documented in the patient's medical history.); or †Is a congenital anomaly/birth defect (in offspring of subject taking the product regardless of time to diagnosis);or Is a new cancer (that is not a condition of the study) (although not serious per ICH definition, is reportable to the Sponsor within 24  hours and to Merck within 2 working days to meet certain local requirements); or Is an overdose (whether accidental or intentional). Any adverse event associated with an overdose is considered a serious adverse  event for collection purposes. An overdose that is not associated with an adverse event is considered a non-serious event of clinical  interest and must be reported within 24 hours to the Sponsor and to Merck within 2 working days.. Other important medical events that may not result in death, not be life threatening, or not require hospitalization may be  considered a serious adverse event when, based upon appropriate medical judgment, the event may jeopardize the subject and may  require medical or surgical intervention to prevent one of the outcomes listed previously (designated above by a †). |           |                                                                                                  |
| Duration                                   | Record the start and stop dates of the adverse event. If less than 1 day, indicate the appropriate length of time and units                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     |           |                                                                                                  |
| Action taken                               | Did the adverse event cause Merck product to be discontinued?                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   |           |                                                                                                  |
| Relationship to                            | Did Merck product cause the adverse event? The determination of the likelihood that Merck product caused the adverse event will                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 |           |                                                                                                  |
| Merck Product                              | be provided by an investigator who is a qualified physician. The investigator's signed/dated initials on the source document or  worksheet that supports the causality noted on the AE form, ensures that a medically qualified assessment of causality was done.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               |           |                                                                                                  |
| CASE 1516  Protocol Amendment 7 06/06/2019 | 57                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              |           |                                                                                                  |  
An investigator who is a qualified physician, will evaluate all adverse events as to:  
| This initialed document must be retained for the required regulatory time frame. The criteria below are intended as reference  guidelines to assist the investigator in assessing the likelihood of a relationship between the test drug and the adverse event based  upon the available information. The following components are to be used to assess the relationship between Merck product and the AE; the greater the  correlation with the components and their respective elements (in number and/or intensity), the more likely Merck product caused  the adverse event (AE):                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     |                                                                                                                                                                                                                              |                                                                                                                                                                                                                                                        |
|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Relationship to Merck Product (continued)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 | Exposure                                                                                                                                                                                                                     | Is there evidence that the subject was actually exposed to Merck product such as: reliable history, acceptable  compliance assessment (pill count, diary, etc.), expected pharmacologic effect, or measurement of  drug/metabolite in bodily specimen? |
| Time Course                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               | Did the AE follow in a reasonable temporal sequence from administration of Merck product?  Is the time of onset of the AE compatible with a drug-induced effect (applies to trials with investigational  medicinal product)? |                                                                                                                                                                                                                                                        |
| Likely Cause                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              | Is the AE not reasonably explained by another etiology such as underlying disease, other drug(s)/vaccine(s), or  other host or environmental factors                                                                         |                                                                                                                                                                                                                                                        |
| The following components are to be used to assess the relationship between the test drug and the AE: (continued) Dechallenge Was Merck product discontinued or dose/exposure/frequency reduced? If yes, did the AE resolve or improve? If yes, this is a positive dechallenge. If no, this is a negative dechallenge. Note: This criterion is not applicable if: (1) the AE resulted in death or permanent disability; (2) the AE  resolved/improved despite continuation of the Sponsor's product; or (3) the trial is a single-dose drug trial);  or (4) Sponsor's product(s) is/are only used one time. Rechallenge Was the subject re-exposed to Merck product in this study? If yes, did the AE recur or worsen? If yes, this is a positive rechallenge. If no, this is a negative rechallenge. Note: This criterion is not applicable if: (1) the initial AE resulted in death or permanent disability, or (2) the  trial is a single-dose drug trial); or (3) Sponsor's product(s) is/are used only one time Note: if a rechallenge is planned for an adverse event which was serious and which may have been caused by  Merck product, or if re-exposure to Merck product poses additional potential significant risk to the subject,  then the rechallenge must be approved in advance by the sponsor as per dose modification guidelines in the  protocol. Consistency with  Trial Treatment  Profile Is the clinical/pathological presentation of the AE consistent with previous knowledge regarding Merck  product or drug class pharmacology or toxicology? |                                                                                                                                                                                                                              |                                                                                                                                                                                                                                                        |
| The assessment of relationship will be reported on the case report forms /worksheets by an investigator who is a qualified physician according to his/her best  clinical judgment, including consideration of the above elements.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         |                                                                                                                                                                                                                              |                                                                                                                                                                                                                                                        |
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8 statistical analysis plan

The primary goal of the trial is to assess the RECIST-defined tumor response rate outside the radiation field in previously treated NSC lung cancer patients given radiation to an index lesion followed by pembrolizumab. Secondary goals include assessment of toxicity, other efficacy measures such as progression-free survival, response duration, overall survival, and local control of disease within the radiation field, immune response, and biomarkers such as PD-L1 expression. In previous studies (KEYNOTE 001 and 010) the overall response rate (ORR) to pembrolizumab monotherapy has been approximately 20% in this population. Based on this an underlying ORR in the current trial >35% would be considered positive whereas a <20% ORR would be considered negative. A two-stage accrual design that allows for early stopping due to lack of efficacy will be employed to test this hypothesis. The maximum accrual goal is 48 eligible and evaluable patients. Initially 29 eligible and evaluable patients will be entered into the trial. If <6 patients respond (observed ORR <21%) the trial will be stopped for (relative) lack of efficacy. If more than 6 patients respond an additional 19 eligible and evaluable patients will be entered. Pembrolizumab plus radiation will be considered effective if overall 12 or more patients respond (ORR >25%). With this design the likelihood of stopping the trial early for lack of efficacy is >64% if the underlying ORR is <20% and <7% if it is >35%. The overall type I and II errors are 20% and 10%, respectively. Safety is an important secondary endpoint. Toxicity will be graded using CTCAE version 4.0 criteria, categorized by organ system, and summarized as frequency counts and percentages. Assuming the trial accrues all 48 patients the risk of a particular type and/or grade of toxicity will be estimable using an exact 90% confidence interval that has a maximum half-width of 13%. The likelihood of observing at least one such event is 86% even if the associated risk is only 5%. Secondary efficacy endpoints such as progression-free survival, response duration, and overall survival will be summarized using the Kaplan-Meier method. Local control will be summarized as a frequency count and percentage. Other endpoints, such as PD-L1 expression, will be summarized as medians and ranges (e.g. proportion of cells expressing PD-L1) or frequency counts and percentages (e.g. number and percent of patient with PD-L1 expression in >50% of cells) as appropriate.  
Methods such as Fisher's exact test, chi-square tests, logistic regression (categorical data), the logrank test and proportional hazards models (time to event data) will be used to compare patient groups. These analyses are primarily exploratory and it is acknowledged that they will have relatively low statistical power. All genomic, transcriptomic, and proteomic molecular analyses will be exploratory. These studies would be analyzed using a prospective-retrospective statistical analysis plan (SAP).
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8.1 pre-planned subset analysis

Preplanned sub-set analysis will be performed based on (1) histology, (2) number of disease sites at the time of study treatment (≤4 versus >4), (3) PD-L1 status (TPS < 50 and TPS ≥ 50) pretreatment, and (4) TILs status on pre-treatment samples.
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9 labeling packaging storage and

The investigator shall take responsibility for and shall take all steps to maintain appropriate records and ensure appropriate supply, storage, handling, distribution and usage of investigational product in accordance with the protocol and any applicable laws and regulations. Clinical Supplies will be provided by Merck as summarized in Table 7.  
| Table 7 - Product Descriptions Product Name & Potency   | Dosage Form                      |
|---------------------------------------------------------|----------------------------------|
| Pembrolizumab 50 mg                                     | Lyophilized Powder for Injection |
| Pembrolizumab 100 mg/ 4mL                               | Solution for Injection           |
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9.2 packaging and labeling information

Clinical supplies will be affixed with a clinical label in accordance with regulatory requirements.
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9.3 clinical supplies disclosure

This trial is open-label, therefore, the subject, the trial site personnel, the Sponsor and/or designee are not blinded to treatment. Drug identity (name, strength) is included in the label text. Random code/disclosure envelopes or lists are not provided.
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9.4 storage and handling requirements

Clinical supplies must be stored in a secure, limited-access location under the storage conditions specified on the label. Receipt and dispensing of trial medication must be recorded by an authorized person at the trial site. Clinical supplies may not be used for any purpose other than that stated in the protocol.
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9.5 returns and reconciliation

The investigator is responsible for keeping accurate records of the clinical supplies received from Merck or designee, the amount dispensed to and returned by the subjects and the amount remaining at the conclusion of the trial. Upon completion or termination of the study, all unused and/or partially used investigational product will be destroyed at the site per institutional policy. It is the Investigator's responsibility to arrange for disposal of all empty containers, provided that procedures for proper disposal have been established according to applicable federal, state, local and institutional guidelines and procedures, and provided that appropriate records of disposal are kept.
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10 administrative and regulatory details

In accordance with the Health Information Portability and Accountability Act (HIPAA), a subject must sign an authorization to release medical information to the sponsor and/or allow the sponsor, a regulatory authority, or Institutional Review Board access to subject's medical information that includes all hospital records relevant to the study, including subjects' medical history. The Principal Investigator of The Case Comprehensive Cancer Center supervises the retention of all documentation of adverse events, records of study drug receipt and dispensation, and all IRB correspondence for as long as needed to comply with local, national and international regulations. No records will be destroyed until the Principal Investigator confirms destruction is permitted.
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10.2 compliance with financial disclosure

All investigators will follow institutional policy for financial disclosure relating to the study and will be in compliance with federal and institutional guidelines for human research studies.
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10.3 compliance with law audit

The study will be conducted in compliance with ICH guidelines and with all applicable federal (including 21 CFR parts 56 & 50), state or local laws.
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10.4 compliance with trial registration

Under the terms of the Food and Drug Administration Modernization Act (FDAMA) and the Food and Drug Administration Amendments Act (FDAAA), the Sponsor of the trial is solely responsible for determining whether the trial and its results are subject to the requirements for submission to the Clinical Trials Data Bank, http://www.clinicaltrials.gov. Information posted will allow subjects to identify potentially appropriate trials for their disease conditions and pursue participation by calling a central contact number for further information on appropriate trial locations and trial site contact information.
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10.5 quality management system

Authorized representatives of the sponsor, a regulatory authority, an Independent Ethics Committee (IEC) or an Institutional Review Board (IRB) may visit the site to perform audits or inspections, including source data verification. The purpose of an audit or inspection is to systematically and independently examine all study-related activities and documents to determine whether these activities were conducted, and data were recorded, analysed, and 06/06/2019 61 accurately reported according to the protocol, Good Clinical Practice (GCP), guidelines of the International Conference on Harmonization (ICH), and any applicable regulatory requirements. For multicenter studies, participating sites must inform the sponsor-investigator of pending audits.
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10.6 data management

The Overture and OnCore™ Databases will be utilized, as required by the Case Comprehensive Cancer Center, to provide data collection for both accrual entry and trial data management. Overture and OnCore™ are Clinical Trials Management Systems housed on secure servers maintained at Case Western Reserve University. Access to data through Overture and OnCore™
is restricted by user accounts and assigned roles. Once logged into the Overture or OnCore™
system with a user ID and password, Overture and OnCore™ define roles for each user which limits access to appropriate data. User information and password can be obtained by contacting the OnCore™ Administrator at OnCore-registration@case.edu.  
Overture and OnCore™ are designed with the capability for study setup, activation, tracking, reporting, data monitoring and review, and eligibility verification. This study will utilize electronic Case Report Form completion in the Overture database. A calendar of events and required forms are available in Overture and OnCore™.
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11 appendices 11.1 common terminology

The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for adverse event reporting. (http://ctep.cancer.gov/reporting/ctc.html)
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11.2 response evaluation criteria in

RECIST version 1.1* will be used in this study for assessment of tumor response. While either CT or MRI may be utilized, as per RECIST 1.1, CT is the preferred imaging technique in this study. * As published in the European Journal of Cancer: E.A. Eisenhauer, P. Therasse, J. Bogaerts, L.H. Schwartz, D. Sargent, R. Ford, J. Dancey, S. Arbuck, S. Gwyther, M. Mooney, L. Rubinstein, L. Shankar, L. Dodd, R. Kaplan, D. Lacombe, J. Verweij. New response evaluation criteria in solid tumors: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47.  
In addition, volumetric analysis will be explored by central review for response assessment.
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appendix i performance status criteria

| ECOG Performance Status Scale                             | Karnofsky Performance Scale                                                                                                                         |                                   |                        |                 |            |     |
|-----------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------|------------------------|-----------------|------------|-----|
| Grade                                                     | Description                                                                                                                                         | Percent                           | Description Normal, no | complaints,     | no         |     |
| 100                                                       | evidence of disease.                                                                                                                                |                                   |                        |                 |            |     |
| 0                                                         | Normal activity. Full active, able to  carry on all pre-disease performance  without restriction.                                                   | Able to carry on normal activity; |                        |                 |            |     |
| 90                                                        | minor                                                                                                                                               | signs                             | or                     | symptoms        | of         |     |
| disease.                                                  |                                                                                                                                                     |                                   |                        |                 |            |     |
| Symptoms, but ambulatory. Restricted                      |                                                                                                                                                     |                                   |                        |                 |            |     |
| 1                                                         | in physically strenuous activity, but  ambulatory and able to carry out work  of a light or sedentary nature (e.g.,  light housework, office work). | Normal activity with effort; some |                        |                 |            |     |
| 80                                                        | signs or symptoms of disease. Cares for self, unable to carry on                                                                                    |                                   |                        |                 |            |     |
| 70                                                        | normal activity or to do active  work.                                                                                                              |                                   |                        |                 |            |     |
| In bed < 50% of the time. Ambulatory                      |                                                                                                                                                     |                                   |                        |                 |            |     |
| 2                                                         | and                                                                                                                                                 | capable                           | of                     | all             | self-care, | but |
| unable                                                    | to                                                                                                                                                  | carry                             | out                    | any             | work       |     |
| activities. Up and about more than  50% if waking hours.  | Requires                                                                                                                                            | occasional                        | assistance,            |                 |            |     |
| 60                                                        | but is able to care for most of  his/her needs. Requires considerable assistance                                                                    |                                   |                        |                 |            |     |
| 50                                                        | and frequent medical care.                                                                                                                          |                                   |                        |                 |            |     |
| In bed > 50% of the time. Capable of                      |                                                                                                                                                     |                                   |                        |                 |            |     |
| 3                                                         | only limited self-care, confined to bed  or chair more than 50% of waking  hours.                                                                   | Disabled,                         | requires               | special         | care       |     |
| 40                                                        | and assistance. Severely disabled, hospitalization                                                                                                  |                                   |                        |                 |            |     |
| 30                                                        | indicated. Death not imminent.                                                                                                                      |                                   |                        |                 |            |     |
| 100%                                                      | bedridden.                                                                                                                                          | Completely                        |                        |                 |            |     |
| 4                                                         | disabled.                                                                                                                                           | Cannot carry on any self                                   |                        |                 |            |     |
| care. Totally confined to bed or chair.                   | 20                                                                                                                                                  | Very                              | sick,                  | hospitalization |            |     |
| indicated. Death not imminent.  Moribund, fatal processes |                                                                                                                                                     |                                   |                        |                 |            |     |
| 10                                                        | progressing rapidly.                                                                                                                                |                                   |                        |                 |            |     |
| 5                                                         | Dead.                                                                                                                                               | 0                                 | Dead                   |                 |            |     |
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