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11.1.3 methods for evaluation of

All measurements should be taken and recorded in metric notation using a ruler, calipers, or a digital measurement tool. All baseline evaluations should be performed as closely as possible to the beginning of treatment and never more than 4 weeks before the beginning of the treatment. The same method of assessment and the same technique should be used to characterize each identified and reported lesion at baseline and during follow-up. Imaging-based evaluation is preferred to evaluation by clinical examination unless the lesion(s) being followed cannot be imaged but are assessable by clinical exam. Clinical lesions. Clinical lesions will only be considered measurable when they are superficial (*e.g.*, skin nodules and palpable lymph nodes) and ≥10 mm in diameter as assessed using calipers (*e.g.*, skin nodules). In the case of skin lesions, documentation by color photography, including a ruler to estimate the size of the lesion, is recommended. Chest x-ray. Lesions on chest x-ray are acceptable as measurable lesions when they are clearly defined and surrounded by aerated lung; however, CT is preferable. Conventional CT and MRI. This guideline has defined measurability of lesions on CT scan based on the assumption that CT thickness is 5mm or less. If CT scans have slice thickness greater than 5 mm, the minimum size of a measurable lesion should be twice the slice thickness. MRI is also acceptable in certain situations (*e.g.* for body scans). Use of MRI remains a complex issue. MRI has excellent contrast, spatial, and temporal resolution; however, there are many image acquisition variables involved in MRI, which greatly impact image quality, lesion conspicuity, and measurement. Furthermore, the availability of MRI is variable globally. As with CT, if an MRI is performed, the technical specifications of the scanning sequences used should be optimized for the evaluation of the type and site of disease. Furthermore, as with CT, the modality used at follow-up should be the same as was used at baseline and the lesions should be measured/assessed on the same pulse sequence. It is beyond the scope of the RECIST guidelines to prescribe specific MRI pulse sequence parameters for all scanners, body parts, and diseases. Ideally, the same type of scanner should be used and the image acquisition protocol should be followed as closely as possible to prior scans. Body scans should be performed with breath-hold scanning techniques, if possible. FDG-PET. While FDG-PET response assessments need additional study, it is sometimes reasonable to incorporate the use of FDG-PET scanning to complement CT scanning in assessment of progression (particularly possible 'new' disease). New lesions on the basis of FDG-PET imaging can be identified according to the following algorithm:
(a) Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD based on a new lesion. (b) No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive FDG-PET at follow-up corresponds to a new site of disease confirmed by CT, this is PD. If the positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, additional follow-up CT scans are needed to determine if there is truly progression occurring at that site (if so, the date of PD will be the date of the initial abnormal FDG-PET scan). If the positive FDG-PET at follow-up corresponds to a pre-existing site of disease on CT that is not progressing on the basis of the anatomic images, this is not PD. (c) FDG-PET may be used to upgrade a response to a CR in a manner similar to a biopsy in cases where a residual radiographic abnormality is thought to represent fibrosis or scarring. The use of FDG-PET in this circumstance should be prospectively described in the protocol and supported by disease-specific medical literature for the indication. However, it must be acknowledged that both approaches may lead to false positive CR due to limitations of FDG-PET and biopsy resolution/sensitivity.  
Note: A 'positive' FDG-PET scan lesion means one which is FDG avid with an uptake greater than twice that of the surrounding tissue on the attenuation corrected image. PET-CT. At present, the low dose or attenuation correction CT portion of a combined PET-CT is not always of optimal diagnostic CT quality for use with RECIST measurements. However, if the site can document that the CT performed as part of a PET-CT is of identical diagnostic quality to a diagnostic CT (with IV and oral contrast), then the CT portion of the PET-CT can be used for RECIST measurements and can be used interchangeably with conventional CT in accurately measuring cancer lesions over time. Note, however, that the PET portion of the CT introduces additional data which may bias an investigator if it is not routinely or serially performed. MIBG (meta-iodobenzylguanidine).The following is recommended, to assure high quality images are obtained. Patient preparation: Iodides, usually SSKI (saturated solution of potassium iodide), are administered to reduce thyroidal accumulation of free radioiodine, preferably beginning the day prior to injection and continuing for 3 additional days (4 days total). For infants and children, one drop t.i.d. is sufficient, for adolescents 2 drops t.i.d., and for adults 3 drops t.i.d. Participants and/or parents are asked about exposure to potential interfering agents. If none is noted, an indwelling intravenous line is established. The dose of MIBG is administered by slow intravenous injection over 90 seconds. Images from the head to the distal lower extremities should be obtained. I-123MIBG scintigraphy is performed to obtain both planar and tomographic images. Planar: Anterior and posterior views from the top of the head to the proximal lower extremities are obtained for 10 minutes at 24 hours and occasionally at 48 hours following injection of 10 mCi/1.7 square meters of body surface area (~150 μCi/kg, maximum 10 mCi). Anterior views of the distal lower extremities are adequate. A large field of view dual head gamma camera with low energy collimators is preferred. SPECT: Most participants receiving I-123 MIBG also undergo SPECT at 24 hours, using a single or multi-headed camera with a low energy collimator. The camera is rotated through 360 degrees, 120 projections at 25 seconds per stop. Data are reconstructed using filtered back projections with a Butterworth filter and a cut off frequency of 0.2-0.5. SPECT/CT may be performed at institutions with this capacity. Ultrasound. Ultrasound is not useful in assessment of lesion size and should not be used as a method of measurement. Ultrasound examinations cannot be reproduced in their entirety for independent review at a later data and, because they are operator dependent, it cannot be guaranteed that the same technique and measurements will be taken from one assessment to the next. If new lesions are identified by ultrasound in the course of the study, confirmation by CT or MRI is advised. If there is concern about radiation exposure from CT, MRI may be used instead of CT in selected instances. Endoscopy, Laparoscopy. The utilization of these techniques for objective tumor evaluation is not advised. However, such techniques may be useful to confirm complete pathological response when biopsies are obtained or to determine relapse in trials where recurrence following complete response (CR) or surgical resection is an endpoint. Tumor markers. Tumor markers alone cannot be used to assess response. If markers are initially above the upper normal limit, they must normalize for a participant to be considered in complete clinical response. Specific guidelines for both CA-125 response (in recurrent ovarian cancer) and PSA response (in recurrent prostate cancer) have been published [*JNCI* 96:487-488, 2004; *J Clin Oncol* 17, 3461-3467, 1999; *J Clin Oncol* 26:1148-1159, 2008]. In addition, the Gynecologic Cancer Intergroup has developed CA-125 progression criteria which are to be integrated with objective tumor assessment for use in first-line trials in ovarian cancer [*JNCI* 92:1534-1535, 2000].  
Cytology, Histology. These techniques can be used to differentiate between partial responses (PR) and complete responses (CR) in rare cases (*e.g.*, residual lesions in tumor types, such as germ cell tumors, where known residual benign tumors can remain). The cytological confirmation of the neoplastic origin of any effusion that appears or worsens during treatment when the measurable tumor has met criteria for response or stable disease is mandatory to differentiate between response or stable disease (an effusion may be a side effect of the treatment) and progressive disease.
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11.1.4 response criteria

11.1.4.1 Evaluation of Target Lesions
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).  
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.  
11.1.4.2 Evaluation of Non-Target Lesions
Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). Note: If tumor markers are initially above the upper normal limit, they must normalize for a patient to be considered in complete clinical response. Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. *Unequivocal progression* should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. Although a clear progression of "non-target" lesions only is exceptional, the opinion of the treating physician should prevail in such circumstances, and the progression status should be confirmed at a later time by the review panel (or Principal Investigator).
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11.1.4.3 evaluation of new lesions

The finding of a new lesion should be unequivocal (i.e. not due to difference in scanning technique, imaging modality, or findings thought to represent something other than tumor (for example, some 'new' bone lesions may be simply healing or flare of pre-existing lesions). However, a lesion identified on a follow-up scan in an anatomical location that was not scanned at baseline is considered new and will indicate PD. If a new lesion is equivocal (because of small size etc.), follow-up evaluation will clarify if it truly represents new disease and if PD is confirmed, progression should be declared using the date of the initial scan on which the lesion was discovered.  
11.1.4.4 Evaluation of Best Overall Response
The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.  
| Target                                                                                       | Non-Target                                                                         | New       | Overall   | Best Overall Response when                       |
|----------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------|-----------|-----------|--------------------------------------------------|
| Lesions                                                                                      | Lesions                                                                            | Lesions   | Response  | Confirmation is Required*                        |
| CR                                                                                           | CR                                                                                 | No        | CR        | >4 wks Confirmation**                            |
| CR                                                                                           | Non-CR/NonPD                                                                                    | No        | PR        | >4 wks Confirmation**                            |
| CR                                                                                           | Not evaluated                                                                      | No        | PR        |                                                  |
| PR                                                                                           | Non-CR/NonPD/not  evaluated                                                                                    | No        | PR        |                                                  |
| SD                                                                                           | Non-CR/NonPD/not  evaluated                                                                                    | No        | SD        | Documented at least once >4  wks from baseline** |
| PD                                                                                           | Any                                                                                | Yes or No | PD        |                                                  |
| Any                                                                                          | PD***                                                                              | Yes or No | PD        | no prior SD, PR or CR                            |
| Any                                                                                          | Any                                                                                | Yes       | PD        |                                                  |
|                                                                                             | See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. |           |           |                                                  |
| **                                                                                           | Only for non-randomized trials with response as primary endpoint.                  |           |           |                                                  |
| ***                                                                                          | In exceptional circumstances, unequivocal progression in non-target lesions may be |           |           |                                                  |
|                                                                                              | accepted as disease progression.                                                   |           |           |                                                  |
| Note: Participants with a global deterioration of health status requiring discontinuation of |                                                                                    |           |           |                                                  |  
Note: Participants with a global deterioration of health status requiring discontinuation of treatment without objective evidence of disease progression at that time should be reported as "*symptomatic deterioration."* Every effort should be made to document the objective progression even after discontinuation of treatment.  
For Participants with Non-Measurable Disease (*i.e.***, Non-Target Disease)**  
| Non-Target Lesions   | New Lesions                                                                                                                                                                                                                                  | Overall Response   |
|----------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------|
| CR                   | No                                                                                                                                                                                                                                           | CR                 |
| Non-CR/non-PD        | No                                                                                                                                                                                                                                           | Non-CR/non-PD*     |
| Not all evaluated    | No                                                                                                                                                                                                                                           | not evaluated      |
| Unequivocal PD       | Yes or No                                                                                                                                                                                                                                    | PD                 |
| Any                  | Yes                                                                                                                                                                                                                                          | PD                 |
|                     | 'Non-CR/non-PD' is preferred over 'stable disease' for non-target disease since SD is  increasingly used as an endpoint for assessment of efficacy in some trials so to assign  this category when no lesions can be measured is not advised |                    |  
11.1.5 Duration of Response Duration of overall response: The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started, or death due to any cause. Participants without events reported are censored at the last disease evaluation). Duration of overall complete response: The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented, or death due to any cause. Participants without events reported are censored at the last disease evaluation. Duration of stable disease: Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements.  
11.1.6 Progression-Free Survival Overall Survival: Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive. Progression-Free Survival: Progression-Free Survival (PFS) is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. Time to Progression: Time to Progression (TTP) is defined as the time from randomization (or registration) to progression, or censored at date of last disease evaluation for those without progression reported.  
11.1.7 Response Review N/a 11.2 Antitumor Effect - **Hematologic Tumors**
N/a 11.3 **Other Response Parameters**
N/a
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12. data reporting / regulatory

Adverse event lists, guidelines, and instructions for AE reporting can be found in Section 7.0 (Adverse Events: List and Reporting Requirements).
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12.1 data reporting

12.1.1 Method The ODQ will collect, manage, and perform quality checks on the data for this study.  
12.1.2 Responsibility for Data Submission Investigative sites within DF/HCC or DF/PCC are responsible for submitting data and/or data forms to the ODQ according to the schedule set by the ODQ.
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12.2 data safety monitoring

The DF/HCC Data and Safety Monitoring Committee (DSMC) will review and monitor toxicity and accrual data from this study. The committee is composed of clinical specialists with experience in oncology and who have no direct relationship with the study. Information that raises any questions about participant safety will be addressed with the Overall PI and study team. The DSMC will review each protocol up to four times a year or more often if required to review toxicity and accrual data. Information to be provided to the committee may include: up-to-date participant accrual; current dose level information; DLT information; all grade 2 or higher unexpected adverse events that have been reported; summary of all deaths occurring with 30 days of intervention for Phase I or II protocols; for gene therapy protocols, summary of all deaths while being treated and during active follow-up; any response information; audit results, and a summary provided by the study team. Other information (e.g. scans, laboratory values) will be provided upon request. 12.3 **Multicenter Guidelines** n/a 12.4 Collaborative **Agreements Language** n/a
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13. statistical considerations 13.1 study

This is an open label Phase II study enrolling patients with MET exon 14 skipping or MET amplification who have previously been treated with a MET inhibitor.  
The primary endpoint is response rate (RR) as measured by RECIST 1.1 criteria. Secondary endpoints are: Progression-Free Survival (PFS): PFS will be defined as the time from the start of study drug to the date of first documented progression or death.  
Disease control rate (DCR): Disease control rate will be defined as the sum of complete response, partial response, and stable disease at 12 weeks by RECIST 1.1.  
Intracranial response rate (IRR): Intracranial response rate will be calculated based on response assessments in the brain for patients with measurable CNS disease at baseline by RECIST v 1.1 criteria.  
Duration of response (DOR): Duration of response will be calculated from the time of first assessment of CR or PR until the first occurrence of progressive disease or death.  
Overall survival (OS): Overall survival will be defined as the time from the start of study drug to the date of death due to any cause. OS time for patients who are alive at the end of hte study or are lost to follow up will be censored at the time of last contact. OS will be estimated using the Kaplan-Meier method.  
Safety and tolerability: Toxicity will be assessed using the CTCAE v4.0 criteria. Exploratory studies will assess biomarkers of response and resistance as well as attempt to establish cell lines and PDX models from optional tumor biopsies.  
All patients who begin study drug on protocol will be considered evaluable. Any patient who does not begin study drug on protocol will be considered not evaluable and will be replaced.
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13.2 sample size accrual rate

The planned sample size is n = 20. Patients who never begin protocol therapy after signing consent or who are not evaluable will be replaced. With n =20 patients, the study will have an 80% power to detect an improvement in the overall response rate of 21.3% from the null of 10% using a one-sided binomial test with alpha of 0.05; i.e. a comparison of response rate of 10% versus 31.3%.
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13.3 stratification factors

No stratification planned 13.4 **Interim Monitoring Plan** The DF/HCC Data and Safety Monitoring Committee (DSMC) will review and monitor toxicity and accrual from this study. 13.5 **Analysis of Primary Endpoints** As described in section 13.1. 13.6 **Analysis of Secondary Endpoints** As described in section 13.1.
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13.7 reporting and exclusions

13.7.1 Evaluation of Toxicity All participants will be evaluable for toxicity from the time of their first treatment.  
13.7.2 Evaluation of the Primary Efficacy Endpoint All participants will be evaluable for response from the time of their first treatment. Participants who never start protocol therapy will be considered inevaluable.
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14. publication plan

The results should be made public within 24 months of reaching the end of the study. The end of the study is the time point at which the last data items are to be reported, or after the outcome data are sufficiently mature for analysis, as defined in the section on Sample Size, Accrual Rate and Study Duration. If a report is planned to be published in a peer-reviewed journal, then that initial release may be an abstract that meets the requirements of the International Committee of Medical Journal Editors. A full report of the outcomes should be made public no later than three (3) years after the end of the study.
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references

[1] American Cancer Society, Cancer Facts and Figures 2015 [2] Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small cell lung cancer. NEJM 2006; 355:2542-2550. [3] Paz-Ares LG, de Marinis F, Dediu M, et al. Paramount: Final overall survival results of the phase 3 study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced non-squamous non-small cell lung cancer. JCO 2013; 2895-2902. [4] Lynch TJ, Bell, DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-39. [5] Paez JG, Janne PA, Lee LC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497-500. [6] Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 2004;101:13306-11. [7] Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non small-cell lung cancer. Nature 2007;448:561-6. [8] Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947-57.  
[9] Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in nonsmall cell lung Anaplastic lymphoma kinase inhibition in non-small cell lung cancer. N Engl J
Med 2010;363:1693-703. [10] Shaw AT, Kim DW, Mehra R, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 2014;370:1189-97. [11] Shaw AT, Ou SH, Bang YJ, et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med 2014;371:1963-71 [12] Ma PC, Jagadeewaran R, Jagadeesh S, et al. Functional expression and mutations of c-met and its therapeutic inhibition with SU11274 and small interering RNA in non-small cell lung cancer. Cancer Res 2005; 65 (4): 1479-88. [13] Kong-Beltran M, Seshagiri S, Zha J, et al. Somatic mutations lead to an oncogenic deletion of met in lung cancer. Cancer Res 2006; 66 (1): 283-9. [14] Onozato R, Kosaka T, Kuwano H, et al. Activation of MET by gene amplification or by splice mutations deleting the juxtamembrane domain in primary resected lung cancers. JTO
2009; 4: 5-11.  
[15] Seo JS, Ju YS, Lee WC, Shin JY, Lee JK, Bleazard T, et al. The transcriptional landscape and mutational profile of lung adenocarcinoma. Genome Res 2012;22:2109-19. [16] Cancer Genome Atlas Research N. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014;511:543-50. [17] Frampton GM, Ali SM, Rosenzweig M, et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Disovery 2015; epub ahead of print. [18] Paik PK, Drilon A, Yu H, et al. Response to MET inhibitors in patients with stage IV lung adenocarcinomas harboring MET mutations causing exon 14 skipping. Cancer Discovery 2015; epub ahead of print. [19] Heist RS. Shim L, Dardaei L, et al. Oncogenic drivers in lung cancer: report of novel transforming fusions including targetable MET exon 14 skipping alterations, manuscript submitted. [20] Mendenhall MA and Goldman JW. JTO 2015; 10 (5): e33-34. [21] Waqar SN, Morgensztern D and Sehn J. MET mutation associated with responsiveness to crizotinib. JTO 2015; 10(5): e29-31. [22] Jenkins RW, Oxnard GR, Elkin S, et al. Response to crizotinib in a patient with lung adenocarcinoma harboring a MET splice site mutation. Clin Lun Cancer 2015; epub ahead of print. [23] Liu X, Jia Y, Stooper MB et al. Next generation sequencing of pulmonary sarcomatoid carcinoma reveals high frequency of actionable met gene mutations. JCO 2015 epub ahead of print. [24] Solomon, B. 2015. MET Amplification in Non-Small Cell Lung Cancer. My Cancer Genome https://www.mycancergenome.org/content/disease/lung-cancer/met/59/ [25] Bang YJ, Su WC, Nam DH, et al (2014) Phase I study of the safety and efficacy of INC280 in patients with advanced MET-dependent solid tumors. J Clin Oncol 32:5s (suppl; abstr 2520.  
[26] Camidge DR, Ou SI, Shapiro G, et al. Efficacy and safety of crizotinib in patients with cMET amplified non-small cell lung cancer. JCO 32:5s, 2014 (suppl; abstr 8001).  
[27] Sequist LV, Heist RS, Shaw AT, et al. Implementing multiplexed genotyping of non-small cell lung cancers in routine clinical practice. Ann Oncol 2011; 22 (12): 2616-24. [28] Gandhi L, Shaw AT, Gadgeel SM, et al. A phase II, open-label, multicenter study of the ALK inhibitor alectinib in an ALK+ non-small-cell lung cancer (NSCLC) U.S./Canadian population who had progressed on crizotinib. J Clin Oncol 33, 2015 (suppl; abstr 8019) [29] Sequist LV, Waltman BA, Dias-Santagata D, et al. Genotypic and histologic evoluation of lung cancers acquiring resistance to EGFR inhibitors. STM 2011; 3 (75): 75ra26. [30] Awad MM, Engelman JA, Shaw AT. Acquired resistance to crizotinib from a mutation in CD74-ROS. NEJM 2013; 369 (12): 1173. [31] Katayama R, Shaw AT, Khan TM, et al. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. STM 2012; 8 (4): 120ra17.  
| 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  performance without restriction. | 90                                                                        | Able to carry on normal activity;  minor signs or symptoms of disease. |
| 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). | 80                                                            | Normal activity with effort; some  signs or symptoms of disease.          |                                                                        |
| 1                                                                                                                                                                                          | 70                                                            | Cares for self, unable to carry on  normal activity or to do active work. |                                                                        |
| In bed <50% of the time.  Ambulatory and capable of all  self-care, but unable to carry out  any work activities. Up and about  more than 50% of waking hours.                             | Requires occasional assistance, but                           |                                                                           |                                                                        |
| 60                                                                                                                                                                                         | is able to care for most of his/her  needs.                   |                                                                           |                                                                        |
| 2                                                                                                                                                                                          | 50                                                            | Requires considerable assistance and  frequent medical care.              |                                                                        |
| In bed >50% of the time. Capable  of only limited self-care, confined  to bed or chair more than 50% of  waking hours.                                                                     | 40                                                            | Disabled, requires special care and  assistance.                          |                                                                        |
| 3                                                                                                                                                                                          | 30                                                            | Severely disabled, hospitalization  indicated. Death not imminent.        |                                                                        |
| 100% bedridden. Completely  disabled. Cannot carry on any  self-care. Totally confined to bed  or chair.                                                                                   | 20                                                            | Very sick, hospitalization indicated.  Death not imminent.                |                                                                        |
| 4                                                                                                                                                                                          | 10                                                            | Moribund, fatal processes  progressing rapidly.                           |                                                                        |
| 5                                                                                                                                                                                          | Dead.                                                         | 0                                                                         | Dead.                                                                  |