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13.4 confidentiality and privacy

Participant confidentiality and privacy is strictly held in trust by the participating investigators, their staff, and the sponsor(s). This confidentiality is extended to cover testing of biological samples and genetic tests in addition to the clinical information relating to participants. Therefore, the study protocol, documentation, data, and all other information generated will be held in strict confidence. No information concerning the study or the data will be released to any unauthorized third party without prior written approval of the sponsor. All research activities will be conducted in as private a setting as possible. The study monitor, other authorized representatives of the sponsor, representatives of the Institutional Review Board (IRB), and/or regulatory agencies may inspect all documents and records required to be maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this study. The clinical study site will permit access to such records. The study participant's contact information will be securely stored at the clinical site for internal use during the study. At the end of the study, all records will continue to be kept in a secure location for as long a period as dictated by the reviewing IRB, Institutional policies, or sponsor requirements. Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be stored at the Center for Cancer Research (CCR). This will not include the participant's contact or identifying information. Rather, individual participants and their research data will be identified by a unique study identification number. The study data entry and study management systems used by clinical sites and by CCR research staff will be secured and password protected. At the end of the study, all study databases will be archived at CCR. To further protect the privacy of study participants, a Certificate of Confidentiality has been issued by the National Institutes of Health (NIH). This certificate protects identifiable research information from forced disclosure. It allows the investigator and others who have access to research records to refuse to disclose identifying information on research participation in any civil, criminal, administrative, legislative, or other proceeding, whether at the federal, state, or local level. By protecting researchers and institutions from being compelled to disclose information that would identify research participants, Certificates of Confidentiality help achieve the research objectives and promote participation in studies by helping assure confidentiality and privacy to participants.
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14 pharmaceutical information 14.1 etbx

The combination ETBX-011, ETBX-051, ETBX-061 vaccine (collectively called as TriAd vaccine) regimen refers to the combination of three investigational adenoviral vaccines. All utilize the same second generation E1(-), E2 (-) vector. Subjects will each receive the three vaccines at the same time, at the same doses, through three separate injections administered in different limbs (proximal limb areas) or separate locations. ETBX-011 is a CEA-targeting vaccine that comprises the Ad5 [E1-, E2b-] vector and a modified CEA (CEA(6D)) gene insert. The investigational product ETBX-061 is a MUC1-targeting vaccine that comprises the Ad5 [E1-, E2b-] vector and a modified MUC1 (MUC1c) gene insert. The investigational product ETBX-051 is a Brachyury-targeting vaccine that comprises the Ad5 [E1-, E2b-] vector and a modified Brachyury gene insert. 14.1.1 Source/Acquisition and Accountability TriAd vaccine will be provided by ImmunityBio (previously NantCell) to the investigator. The investigator or designee (e.g. pharmacist) will maintain an ongoing inventory of the investigational product supply according to standard site procedures. The investigational product will be dispensed at the direction of an investigator for administration to a study participant enrolled on the clinical trial. Disposal of expired or unused product will be returned to the manufacturer or disposed of according to standard site procedures based on agreement between the manufacturer and the site.  
14.1.2 Dosage Form:  
| Suspension for injection  Product Name   | ETBX-011 (Ad5 [E1-, E2b-]-CEA(6D) Vaccine)                                                                                                                                                                                                                                                                                                                                     |
|------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Dose                                     | 5 x 1011 VP (standard dose)                                                                                                                                                                                                                                                                                                                                                    |
| Route of Administration                  | SC injection  ETBX vaccine is supplied as a sterile, clear solution in a 2-mL  single-dose vial. The vaccine is provided at a concentration of 5 x  1011 VP per 1 mL and contains ARM formulation buffer (20 mM  TRIS, 25 mM NaCl, 2.5% glycerol, pH 8.0). Each vial contains  approximately 1.3 mL of the vaccine. ETBX-011 should be stored  at ≤ -60°C until ready for use. |
| Physical Description  Manufacturer       | Etubics (a wholly owned subsidiary of ImmunityBio Inc., formerly  known as NantCell, Inc; hereafter referred to as Immunity Bio )                                                                                                                                                                                                                                              |
| Product Name(s):                         | ETBX-061 (Ad5 [E1-, E2b-]-MUC1 Vaccine)                                                                                                                                                                                                                                                                                                                                        |
| Dosage Form:                             | Suspension for injection                                                                                                                                                                                                                                                                                                                                                       |
| Dose                                     | 5 x 1011 VP (standard dose)                                                                                                                                                                                                                                                                                                                                                    |
| Route of Administration                  | SC injection  ETBX vaccine is supplied as a sterile, clear solution in a 2-mL  single-dose vial. The vaccine is provided at a concentration of 5 x  1011 VP per 1 mL and contains ARM formulation buffer (20 mM  TRIS, 25 mM NaCl, 2.5% glycerol, pH 8.0). Each vial contains1  mL of extractable vaccine. The product should be stored at ≤ -60°C  until ready for use.       |
| Physical Description  Manufacturer       | ImmunityBio (previously NantCell)                                                                                                                                                                                                                                                                                                                                              |
| Product Name(s):                         | ETBX-051 (Ad5 [E1-, E2b-]-Brachyury Vaccine)                                                                                                                                                                                                                                                                                                                                   |  
| Dosage Form:                       | Suspension for injection                                                                                                                                                                                                                                                                                                                                                  |
|------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Dose                               | 5 x 1011 VP (standard dose),                                                                                                                                                                                                                                                                                                                                              |
| Route of Administration            | SC injection  ETBX vaccine is supplied as a sterile, clear solution in a 2-mL  single-dose vial. The vaccine is provided at a concentration of 5 x  1011 VP per 1 mL and contains ARM formulation buffer (20 mM  TRIS, 25 mM NaCl, 2.5% glycerol, pH 8.0). Each vial contains 1  mL of extractable vaccine. The product should be stored at ≤ -60°C  until ready for use. |
| Physical Description  Manufacturer | ImmunityBio (previously NantCell)                                                                                                                                                                                                                                                                                                                                         |  
14.1.3 Source The manufacturing department of ImmunityBio (previously NantCell) will supply each vaccine in 2-mL single-dose vials. Each single-dose vial contains a sterile, clear suspension of the ETBX
vaccine at 5 x 1011 VP per 1 mL intended for single dose administration and contains ARM
formulation buffer (20 mM TRIS, 25 mM NaCl, 2.5% glycerol, pH 8.0). Upon receipt of the investigational product, the Investigator or delegated designee will verify that an appropriate shipping temperature was maintained, conduct an inventory, and sign the drug receipt form and send a scanned copy to the Sponsor contact as designated on the form. If a temperature excursion occurs, the Sponsor should be notified immediately, and the investigational product must be quarantined and maintained under the correct storage conditions until further instructions are provided by the Sponsor. The temperature excursion form will need to be completed and returned to the Sponsor. The original drug receipt form and packing slip must be retained in the Investigator's pharmacy records.
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14.1.4 toxicity

The safety of immunizations (injections) with the ETBX-011, ETBX-051, ETBX-061 has been established in a phase I clinical trial. Ten subjects enrolled and no DLTs were observed. Common TRAEs were fever and injection site reactions, all grade 1 or 2.
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14.1.5 formulation and preparation

Each vaccine is supplied as a clear colorless liquid filled in a 2-mL amber vial at a concentration of 5x1011 total virus particles (VP) per 1.0 mL. Each vial is sealed with a rubber stopper and has a white flip off seal. End user of the product will need to flip the white plastic portion of the cap up/off with their thumb to expose the rubber stopper, and then puncture the stopper with an injection needle to withdraw the liquid. The rubber stopper is secured to the vial with an aluminum crimped seal.
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14.1.6 stability and storage

Individual vials (in the desired number) of vaccine will be packaged in a cardboard box and will be shipped over dry ice by overnight courier with a temperature monitoring device included. Upon receipt, one will inspect contents of package for any noticeable damages or defects. Unpack the shipment contents and place the cardboard box containing vaccine vials into a freezer with a monitored temperature control. ETBX-011, ETBX-051 and ETBX-061 vials should be stored at ≤ -60°C. Receiver must stop the temperature monitoring device by turning off the power switch (instructions for handling and operation of temperature monitoring device will be provided with the package).
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14.1.7 etbx dose preparation and

The dose of ETBX vaccine to be injected is 5x1011 VP per 1mL. Prior to injection, the appropriate vial should be removed from the freezer and allowed to thaw at controlled room temperature (20–25°C, 68-77°F) for at least 20 minutes and not more than 30 minutes, after which it should be kept at 2-8°C (35–46°F). The vaccine is stable in the vial for at least 8 hours after removal from the freezer when kept refrigerated at 2-8°C (35-46°F). Once the vaccine has been thawed, it must not be refrozen. Each vial is sealed with a rubber stopper and has a white flip-off seal. The end user of the product will need to flip the white plastic portion of the cap up/off with their thumb to expose the rubber stopper and then puncture the stopper with an injection needle to withdraw the liquid. The rubber stopper is secured to the vial with an aluminum-crimped seal. The thawed vial should be swirled and then, using aseptic technique, the pharmacist or pharmacist designee should withdraw the appropriate volume from the appropriate vial using an appropriately sized syringe. The thawed drug product may be stored at 2 - 8°C in the vial or syringe for a total of up to 8 hours prior to delivery to the patient, if necessary. *Instructions for Dose Preparation - 5 x 1011* Virus Particles Withdraw 1 mL of contents from the vial, prepare the injection site with alcohol, and administer to the subject by SC injection without any further manipulation (refer to the vial label for a description of the vialed ETBX vaccine concentration). 14.1.8 Administration Please refer to section 3.2.3. 14.1.9 Other Information The Ad5 [E1-, E2b-] vector is non-replicating and its genome does not integrate into the human genome. However, since this is a non-replicating recombinant virus, it is recommended that it be handled under Biosafety Level-2 conditions. Any vialed ETBX vaccine material that has been used in the study should be autoclaved or incinerated after use according to institutional policy and according to local, state and federal regulations.  
Version Date: *August 31, 2022* 14.1.10 Incompatibilities None known
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14.2 m7824 (bintrafusp alfa msb0011359c)

M7824 is manufactured and supplied for the trial by EMD Serono Research and Development Institute. The investigator or designee (e.g. pharmacist) will maintain an ongoing inventory of the investigational product supply according to standard site procedures. The investigational product will be dispensed at the direction of an investigator for administration to a study participant enrolled on the clinical trial. Disposal of expired or unused product will be returned to the manufacturer or disposed of according to standard site procedures based on agreement between the manufacturer and the site.
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14.2.2 toxicity

In a phase 1, open-label 3+3 dose-escalation study of M7824 in 16 patients, 3 patients experienced grade 3 drug-related adverse events including skin infection secondary to grade 2 bullous pemphigoid, lipase increased, and colitis with associated anemia. There was no grade 4 - 5 treatment related adverse events. Please see table below for details: Treatment-related TEAE Leading to Permanent Treatment Discontinuation by System Organ Class and Preferred Term in ≥ **2 participants in the Pooled Analysis of Dose** Expansion Cohorts (Source: Investigator Brochure v6)  
| Version Date: August 31, 2022                                                               | EMR200647-001   | MS200647-0008   | Total      |
|---------------------------------------------------------------------------------------------|-----------------|-----------------|------------|
| Primary System Organ Class                                                                  | (N = 539)       | (N = 630)       |            |
| ( = 91)                                                                                     |                 |                 |            |
| Dictionary-Derived Term                                                                     | N (%)           | N (%)           | N (%)      |
| Participants with any SAE                                                                   | 31 (59.6)       | 50 (54.9)       | 371 (58.9) |
| Blood and lymphatic system                                                                  | 27 (5.0)        | o               | 27 (4.3)   |
| disorders                                                                                   |                 |                 |            |
| Anaemia                                                                                     | 19 (3.5)        | 19 (3.0)        |            |
| Endocrine disorders                                                                         | 1 (2.0)         | 2 (2.2)         | 13 (2.1)   |
| Adrenal insufficiency                                                                       | 5 (0.9)         | 2 (2.2)         | 7 (1.1)    |
| Gastrointestinal disorders                                                                  | 64 (11.9)       | 13 (14.3)       | 7 (12.2)   |
| Abdominal pain                                                                              | 5 (0.9)         | 1 (1.1)         | 6 (1.0)    |
| Gastrointestinal haemorrhage                                                                | 7 (1.3)         | 1 (1.1)         | 8 (1.3)    |
| Upper gastrointestinal                                                                      | 2 (0.4)         | 4 (4.4)         | 6 (1.0)    |
| haemorrhage                                                                                 |                 |                 |            |
| Vomiting                                                                                    | 6 (1.1)         | 6 (1.0)         |            |
| General disorders and administration                                                        | 70 (13.0)       | 10 (11.0)       | 80 (12.7)  |
| site conditions                                                                             |                 |                 |            |
| Disease progression                                                                         | 43 (8.0)        | 6 (6.6)         | 49 (7.8)   |
| General physical health                                                                     | 6 (1.1)         | 0               | 6 (1.0)    |
| deterioration                                                                               |                 |                 |            |
| Pyrexia                                                                                     | 8 (1.5)         | 1 (1.1)         | 9 (1.4)    |
| 18 (2.9)                                                                                    |                 |                 |            |
| Hepatobiliary disorders                                                                     | 10 (1.9)        | 8 (8.8)         |            |
| Cholangitis                                                                                 | 2 (0.4)         | 5 (5.5)         | 7 (1.1)    |
| 63 (10.0)                                                                                   |                 |                 |            |
| Infections and infestations                                                                 | 54 (10.0)       | 9 (9.9)         |            |
| Pneumonia                                                                                   | 14 (2.6)        | 3 (3.3)         | 17 (2.7)   |
| Sepsis                                                                                      | 8 (1.5)         | 8 (1.3)         |            |
| Metabolism and nutrition disorders                                                          | 25 (4.6)        | 3 (3.3)         | 28 (4.4)   |
| Decreased appetite                                                                          | 5 (0.9)         | 3 (3.3)         | 8 (1.3)    |
| Neoplasms benign, malignant and                                                             | 61 (11.3)       | 8 (8.8)         | 69 (11.0)  |
| unspecified (incl cysts and polyps)                                                         |                 |                 |            |
| Keratoacanthoma                                                                             | 9 (1.7)         | o               | 9 (1.4)    |
| Squamous cell carcinoma of skin                                                             | 2 (4.1)         | 1 (1.1)         | 23 (3.7)   |
| Tumour haemorrhage                                                                          | 8 (1.5)         | 2 (2.2)         | 10 (1.6)   |
| Renal and urinary disorders                                                                 | 14 (2.6)        | 14 (2.2)        |            |
| o                                                                                           |                 |                 |            |
| Acute kidney injury                                                                         | 10 (1.9)        | 0               | 10 (1.6)   |
| Respiratory, thoracic and mediastinal                                                       | 68 (12.6)       | 6 (6.6)         | 74 (11.7)  |
| disorders                                                                                   |                 |                 |            |
| Dyspnoea                                                                                    | 26 (4.8)        | o               | 26 (4.1)   |
| Pneumothorax                                                                                | 6 (1.1)         | 1 (1.1)         | 7 (1.1)    |
| Pulmonary embolism                                                                          | 9 (1.7)         | 9 (1.4)         |            |
| As of the data cutoff of 24 August 2018, 7 deaths (1.1%) were reported as due to treatment- |                 |                 |            |  
related TEAE, however an additional death (primary cause of intra-abdominal hemorrhage, assessed as treatment-related) started more than 30 days after the end of treatment and is therefore is not included in above count of treatment-related death. In Study EMR200647-001, 3 participants had a treatment-related death: 1 participant had dyspnea, hemolysis and thrombocytopenia, 1 participant had an intracranial tumor hemorrhage and 1 participant had pneumonia. In Study MS200647-0008, 4 participants had a treatment-related death: 2 participants died due to ILD, 1 participant due to sudden death and 1 participant due to septic shock. Please refer to IB v 6.0 Section 5.2.2.9 for a summary of the SAEs from the Sponsor's Global Drug Safety database from 25 August 2018 to 31 December 2019 for ongoing studies.  
In addition, at least 2 instances of nodular regenerative hyperplasia have been observed with the use of this agent Important identified risks have been identified as IRRs including hypersensitivity, irAEs and skin lesions with hyperkeratosis, keratoacanthoma, cutaneous squamous cell carcinoma possibly due to TGFβ inhibition. The important identified risks with M7824 (bintrafusp alfa) observed to date were overall manageable. Anemia, alterations in wound healing or repair of tissue damage, and embryofetal toxicity remain as important potential risks. Mucosal bleeding events of mild to moderate severity were observed in participants treated with M7824 in ongoing studies and are a potential risk for M7824. Events may include epistaxis, hemoptysis, gingival bleeding or hematuria amongst others. In general, these reactions resolve without discontinuation of treatment. In addition, after discussion among NCI investigators on multiple protocols using M7824, multiple bleeding events ranging from low grade gingival bleeding and epistaxis to more serious hemoptysis, GI bleeding and hematuria have been observed. Some of these events can be attributed to bleeding events related to cancer directly and others bleeding events can be attributed to colitis or cystitis which is a known toxicity of anti-PD-L1 agents including M7824. However, there remains the possibility that M7824 may increase the overall risk of bleeding in ways that may not be directly related to direct tumor bleeding or inflammatory bleeding events described with checkpoint inhibitors like M7824. It is hypothesized that this possible increased bleeding risk may be due to TGF beta inhibition which has an effect on angiogenesis; bleeding has also been observed in patients receiving M7824 and may be drug-related (e.g., gum bleeding, nose bleeds, coughing up blood, blood in their urine, or blood in the stool). Accordingly, patients will be notified of the same possible risk in the informed consent document for this study (e.g., gum bleeding, nose bleeds, coughing up blood, blood in their urine, or blood in the stool).  
Several procedures have been performed on patients receiving M7824 at the NCI and no bleeding complications have been reported.  
| bleeding complications have been reported. Procedure   | Number of patients   |
|--------------------------------------------------------|----------------------|
| Percutaneous cholecystostomy                           | 1                    |
| Nephrostomy tube placement                             | 1                    |
| Liver biopsy                                           | 5                    |
| Thoracentesis                                          | 1                    |
| Biliary stent placement                                | 1                    |
| Epidural catheter                                      | 2                    |
| Tracheostomy                                           | 1                    |
| Resection of CNS metastasis                            | 1                    |
| Endoscopic biopsies under anesthesia                   | 10                   |  
| (13 biopsies per occurrence) Complete debridement of papillomas   | 4   |
|-------------------------------------------------------------------|-----|  
14.2.3 Formulation and Preparation M7824 is provided as a sterile liquid formulation and packaged at a 10 mg/mL concentration in USP/ Ph Eur type I 50R vials that are filled with drug product solution to allow an extractable volume of 60 mL (600 mg/60 mL). The vials are closed with rubber stoppers in serum format complying with USP and Ph Eur with an aluminum crimp seal closure. Each single-use vial contains 600mg of M7824, formulated as 10mg/mL of active, 6% (w/v) Trehalose, 40 mM NaCl, 5 mM Methionine, 0.05% (w/v) Tween 20, 10 mM LHistidine at pH 5.5. The liquid formulation is diluted directly with 0.9% sodium chloride solution for injection. The estimated volumes of delivery are anticipated to be no more than 250mL. The verified concentration range in the infusion solution is 0.16 mg/mL to 9.6 mg/mL.
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14.2.4 stability and storage

M7824 must be stored at 2℃ to 8℃ until use. Product stored at room temperature for extended periods of time might be subject to degradation. M7824 must not be frozen. Rough shaking of the reconstituted solution must be avoided. The chemical and physical in-use stability for the infusion solution of M7824 in 0.9% sodium chloride for injection has been demonstrated for a total of 72 hours at room temperature; however, from a microbiological point of view, the diluted solution should be used immediately and is not intended to be stored unless dilution has taken place in controlled and validated aseptic conditions. No other drugs should be added to the infusion containers containing M7824. 14.2.5 Administration procedures See section 3.2.2. 14.2.6 Incompatibilities None known
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14.3 n-803 (alt-803) 14.3.1 acquisition

N-803 is manufactured and supplied by ImmunityBio (previously NantCell) to the Investigator. The investigator or designee (e.g. pharmacist) will maintain an ongoing inventory of the investigational product supply according to standard site procedures. The investigational product will be dispensed at the direction of an investigator for administration to a study participant enrolled on the clinical trial. Disposal of expired or unused product will be returned to the manufacturer or disposed of according to standard site procedures based on agreement between the manufacturer and the site.
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14.3.2 toxicity

In patients receiving the 10 mcg/kg subcutaneous injection, the following were reported grade 1 and 2 toxicities: worsening anemia, diarrhea, anorexia, nausea/vomiting, constipation, fatigue, fever, peripheral IV infiltration, injection site reactions, pain/aches, sinusitis, hypoalbuminemia, hypocalcemia, hypophosphatemia, decreased iron, headaches, dysgeusia, atrial fibrillation, and cough. Grade 3 hypertension, atrial fibrillation, neutropenia, and decreased lymphocyte count were also reported.
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14.3.3 formulation and preparation

N-803 is a soluble complex consisting of two protein subunits of a human IL-15 variant associated with high affinity to a dimeric human IL-15 receptor α (IL-15Rα) sushi domain/human IgG1 Fc fusion protein. The IL-15 variant is a 114 aa polypeptide comprising the mature human IL-15 cytokine sequence with an Asn to Asp substitution at position 72 of helix C (N72D). The human IL-15Rα sushi domain/human IgG1 Fc fusion protein comprises the sushi domain of the human IL-15 receptor α subunit (IL-15Rα) (aa 1-65 of the mature human IL-15Rα protein) linked with the human IgG1 CH2-CH3 region containing the Fc domain (232 amino acids). Aside from the N72D substitution, all of the protein sequences are human. Based on the amino acid sequence of the subunits, calculated molecular weight of complex comprising two IL-15N72D polypeptides and a disulfide linked homodimeric IL-15RαSu/IgG1 Fc protein is 92.4 kilodaltons (kDa). Each IL-15N72D polypeptide has a calculated molecular weight of approximately 12.8 kDa and the IL-15RαSu/IgG1 Fc fusion protein has a calculated molecular weight of approximately 33.4 kDa. Both the IL-15N72D and IL-15RαSu/IgG1 Fc proteins are glycosylated resulting in an apparent molecular weight of N-803 as approximately 113 kDa by size exclusion chromatography. The isoelectric point (pI) determined for N-803 ranges from approximately 5.5 to 6.5. Thus, the fusion protein is negatively charged at pH 7. The calculated molar extinction coefficient at A280 for N-803 is 116,540 M-1, or 1.26 OD280 for a 1 mg/mL solution of N-803, or one OD280 is equivalent to 0.79 mg/mL solution of N-803. The biological drug product, N-803, is formulated in a phosphate buffered saline solution. The drug substance is produced by a recombinant mammalian cell line and is manufactured using protein-free media.  
N-803 is supplied in a 2-mL single-dose/single-use vial containing 0.6 mL of N-803 (extractable volume is 0.5 mL) at a concentration of 1 mg/mL or 2 mg/mL.
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14.3.4 stability and storage

Study medication is provided in a 2mL vial containing 0.6 mL of ALT 803 at a concentration of 2 mg/mL. Study medication must be maintained at a temperature between 2℃ and 8℃. The duration of time during which the product remains stable at room temperature will be obtained from ImmunityBio (previously NantCell). 14.3.5 Administration procedures N-803 is administered subcutaneously. See section 3.2.4 Version Date: *August 31, 2022* 14.3.6 Incompatibilities None known
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| APPENDIX A: -PERFORMANCE STATUS CRITERIA ECOG Performance Status Scale Karnofsky Performance Scale Grade Descriptions Percent Description 100 Normal, no complaints,   | no                                                                                                    |                                                                                                           |                                                              |                 |             |                                   |                                 |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------|--------------------------------------------------------------|-----------------|-------------|-----------------------------------|---------------------------------|
| evidence of disease.                                                                                                                                                   |                                                                                                       |                                                                                                           |                                                              |                 |             |                                   |                                 |
| Normal activity. Fully active, able                                                                                                                                    |                                                                                                       |                                                                                                           |                                                              |                 |             |                                   |                                 |
| 0                                                                                                                                                                      | to                                                                                                    | carry                                                                                                     | on                                                           | all             | pre-disease | Able to carry on normal activity; |                                 |
| performance without restriction.                                                                                                                                       | 90                                                                                                    | minor                                                                                                     | signs                                                        | or              | symptoms    | of                                |                                 |
| disease. Normal                                                                                                                                                        | activity                                                                                              | with                                                                                                      | effort;                                                      |                 |             |                                   |                                 |
| 80                                                                                                                                                                     | some                                                                                                  | signs                                                                                                     | or                                                           | symptoms        | of          |                                   |                                 |
| disease.                                                                                                                                                               |                                                                                                       |                                                                                                           |                                                              |                 |             |                                   |                                 |
| 1                                                                                                                                                                      | Symptoms,                                                                                             | but                                                                                                       | ambulatory.                                                  |                 |             |                                   |                                 |
| Restricted in physically strenuous  activity, but ambulatory and able  to carry out work of a light or  sedentary nature (e.g., light  housework, office work).        | 70                                                                                                    | Cares for self, unable to carry on  normal activity or to do active  work. Requires occasional assistance |                                                              |                 |             |                                   |                                 |
| In                                                                                                                                                                     | bed                                                                                                   | <50%                                                                                                      | of                                                           | the             | time.       | 60                                | but is able to care for most of |
| Ambulatory and capable of all                                                                                                                                          | his/her needs.                                                                                        |                                                                                                           |                                                              |                 |             |                                   |                                 |
| 2                                                                                                                                                                      | self-care, but unable to carry out  any work activities. Up and about  more than 50% of waking hours. | 50                                                                                                        | Requires considerable assistance  and frequent medical care. |                 |             |                                   |                                 |
| 40                                                                                                                                                                     | Disabled, requires special care  and assistance.                                                      |                                                                                                           |                                                              |                 |             |                                   |                                 |
| In bed >50% of the time. Capable  of only limited self-care, confined  to bed or chair more than 50% of                                                                | Severely                                                                                              | disabled,                                                                                                 |                                                              |                 |             |                                   |                                 |
| waking hours.                                                                                                                                                          | 30                                                                                                    | hospitalization indicated. Death  not imminent.                                                           |                                                              |                 |             |                                   |                                 |
| 3                                                                                                                                                                      | 20                                                                                                    | Very                                                                                                      | sick,                                                        | hospitalization |             |                                   |                                 |
| indicated. Death not imminent.                                                                                                                                         |                                                                                                       |                                                                                                           |                                                              |                 |             |                                   |                                 |
| 4                                                                                                                                                                      | 100%                                                                                                  | bedridden.                                                                                                | Completely                                                   |                 |             |                                   |                                 |
| disabled. Cannot carry on any  self-care. Totally confined to bed  or chair.                                                                                           | 10                                                                                                    | Moribund,                                                                                                 | fatal                                                        | processes       |             |                                   |                                 |
| progressing rapidly.                                                                                                                                                   |                                                                                                       |                                                                                                           |                                                              |                 |             |                                   |                                 |
| 5                                                                                                                                                                      | Dead.                                                                                                 | 0                                                                                                         | Dead.                                                        |                 |             |                                   |                                 |