TABLE 2.

Proposed endpoints for clinical trials in sarcoidosis (5, 21, 22).

Organ involvement	Domain	Measure	Comments
Pulmonary sarcoidosis	**Symptoms	Dyspnea—mMRC, BDI/TDI Cough—Leicester scale Fatigue—FAS	This should be customized to capture multi-organ and/or extra pulmonary involvement.
	*Physician judgment	Clinical judgment of improvement, worsening or progression.	This is applicable to systemic and all organ-specific forms of sarcoidosis.
	*Steroid sparing	% Reduction in steroid dose, Cumulative steroid dose, Duration of time at minimal steroid doses, % Of participants able to achieve steroid taper to < 10 mg/day.	Consider analyzing drop-out from placebo arm as a secondary outcome. Confounding results may occur from withdrawal from steroid or flare-ups in non-target organs. Measures of steroid toxicity and ways of addressing them need to be put in place.
	Radiology/evidence of activity	Changes in PET/CT chest imaging	Changes in PET scans will need to be defined in terms of SUVmean or SUVmax. There is a need to determine what constitutes a meaningful difference in SUV levels.
	*Medication toxicity/tolerance	Serious AEs, Life threatening AEs, AEs leading to discontinuation of therapy Other AEs	This should be captured in all clinical trials and tailored to investigational drugs and organ system targeted.
	Pulmonary function	FEV1, FVC, DLCo, CPI	There is a need to determine what is clinically meaningful disease specific change in FVC, FEV1 and DLCo for patients with pulmonary sarcoidosis. The CPI has also been validated as a prognostic severity marker in pulmonary sarcoidosis.
	Exercise capacity	6MWD	There is a need to determine what constitutes meaningful change in 6MWD for patients with pulmonary sarcoidosis.
	*HRQoL	SGRQ, SF-36, SAT-Lung FAS KSQ General Health; KSQ Lung	Various PROMs have been used to capture HRQoL. There is a need to create core sets of outcome measures for organ specific and systemic sarcoidosis.
	Mortality	Mortality often not feasible Consider composite outcome—TTCW	TTCW is a predefined composite endpoint that can be customized to capture such events as disease-related hospitalization, all-cause hospitalization, death, transplantation, worsening of 6MWD, PFT or symptom burden.
Cutaneous Sarcoidosis	Cutaneous sarcoidosis disease activity HRQoL	PGA, SASI, CSAMI, Photographs SAT skin, KSQ Dermatology Questionnaire, SAT Fatigue
Cardiac Sarcoidosis	Symptoms Radiology/Evidence of Disease Activity Exercise Capacity Mortality	Arrythmias/arrythmia burden cPET Scan, cMRI, Echocardiogram (LVEF) 6MWD Mortality is often not feasible. Consider composite outcomes assessing all-cause hospitalization, cardiac hospitalization,	Note that mortality will likely never be feasible in view of rarity of disease and much improved prognosis. Though composite outcomes are more achievable, sample size is likely to be prohibitive in view of rarity of disease and much improved prognosis.
Neurosarcoidosis	Imaging/evidence of disease activity HRQoL	MRI Measures assessing cognitive functioning, Functional independence, strength measures of limbs, General Health status questionnaires.
Others Ocular Renal Hypercalcemia	HRQoL measures	General and organ specific HRQoL measures	This can be customized for each organ involved.

**Should be customized to reflect the specific organ(s) of interest.

*Applicable to all organ manifestations of disease.

HRQoL, health related quality of life; TTCW, time to clinical worsening; PFT, pulmonary function tests, FVC, forced vital capacity; FEV1, forced expiratory volume in 1 second; DLCo, diffusion capacity for carbon monoxide; SGRQ, Sant Georges Respiratory Questionnaire; SF-36, Short form-36; SAT-Lung, sarcoidosis assessment test lung component; FAS, fatigue assessment score; KSQ, Kings sarcoidosis questionnaire; mMRC, modified Medical Research Council; BDI/TDI, baseline dyspnea index/Transitional dyspnea index; PET/CT, positron emission tomography/computed tomography scan; cPET, cardiac PET scan; SUV, standardized uptake Value; MRI, magnetic resonance imaging; cMRI, cardiac MRI; AE, Adverse event; 6MWD, 6-min walk distance; PGA, Physician Global Assessment; SASI, sarcoidosis activity and severity instrument; CSAMI, cutaneous sarcoidosis activity and morphology instrument; LVEF, left ventricular Ejection Fraction; CPI, composite physiological index; a weighted index of pulmonary function variables.