Categories	Elements	Definition	Ranking
Nature of treatment	Mechanism of action	The specific process through which a treatment produces its effect (e.g., through delivering a gene to liver cells in the case of gene therapy; or through delivering factor to the body in the case of factor replacement therapy)
Administration	Route of administration	The path by which a treatment is administered to the body (e.g., oral, intravenous, subcutaneous)
	Dose frequency	The number of times a treatment is administered within a specific time period (e.g., twice per week, once per year)
	Duration of administration	The amount of time needed to complete one administration (e.g., 15 min, 1 h)
	Dosage strength	The strength of a treatment, which indicates the amount of active ingredient in each dosage (e.g., concentration of factor, concentration of vectors)
	Place of administration	The geographical place where the treatment is administered (e.g. at home, hospital)
	Ease of administration	The degree of ease to perform an administration
	Ease of product storage	The degree of ease to store a treatment (e.g., the amount of storage space needed, temperature requirements)
Follow‐up	Frequency of monitoring	The number of times a patient has to visit a physician for follow‐up on the effect of the treatment within a specific time period (e.g. once per month, once per year)
Benefits	Effect on factor level	The effect on the amount of working clotting factor in the blood, delivered via factor replacement therapy or produced by the patient after gene therapy (often expressed in percentage, %, of normal levels)
	Effect on annual bleeding rate	The effect of the treatment on the number of bleeding events per year
	Probability that prophylaxis can be stopped after treatment	The chance that use of prophylactic factor replacement therapy can be stopped after treatment (expressed in percentage, %, of patients that can stop prophylaxis)
	Uncertainty regarding long‐term benefits	The degree of uncertainty that the effect of the treatment will be maintained after administration of the treatment (uncertainty may exist because of limited time that patients were followed‐up after treatment administration, or because of limited numbers of patients treated with the treatment)
Quality of Life	Impact on daily life	The impact of the treatment on daily activities
	Impact on participation in physical activity	The impact of the treatment on the performance of physical activity (sports)
	Possibility to undergo major surgery	The impact of the treatment on the possibility to undergo major surgery
Risks	Probability that liver inflammation will develop	The chance that liver inflammation develops after treatment (expressed in percentage, %, of patients that develops liver inflammation)
	Uncertainty regarding long‐term risks	The degree of uncertainty regarding the side effects that can occur after administration of the treatment (uncertainty may exist because of limited time that patients were followed‐up after treatment administration, or because of limited numbers of patients treated with the treatment)
Spontaneously mentioned elements