Table 2.

Patient priorities for input mapped onto the decision uncertainty matrix

Step in technology lifecycle	Type of uncertainty
	Clinical benefit	Value for money	Affordability	Adoption/diffusion
Pre-clinical phase	Patient registries Providing data  Develop or initiate registries [C (indirect); D (direct)]  Provide information on the disease and its impact on patients and families through natural history registries [C (indirect); D (direct)]
	Value definition Designing endpoints Provide input in the creation of endpoints that are relevant, meaningful, and functional [C (direct); D (direct)]
	Early studies and drug discovery Input into research decisions Guide decisions regarding research priorities [C (indirect); D (indirect)]
Clinical trials	Patient registries Providing data  Provide information through natural history registries [A (indirect); C (indirect); D (direct); E (indirect); F (indirect)] B (indirect)?  Report on outcomes when receiving treatment [A (indirect); B (direct); E (direct)]  Provide ‘subjective’ data, such as patient-reported outcomes (PROs) and patient satisfaction [A (indirect); B (direct); E (direct); F (indirect)]	Patient registries Providing data  Provide information through natural history registries [A (indirect); E (indirect); F (indirect); G (indirect); J (direct)]  Report on outcomes when receiving treatment [A (direct); B (direct); E (direct); G (indirect); J (direct)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (direct); B (direct); E (direct); F (indirect); G (indirect); J (direct)]	Patient registries Providing data  Provide information through natural history registries [A (indirect); J (direct)]  Report on outcomes when receiving treatment [A (indirect); J (direct)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (indirect); J (direct)]	Patient registries Providing data  Provide information through natural history registries [A (indirect); J (direct)]  Report on outcomes when receiving treatment [A (indirect); L (indirect); M (indirect); N (direct)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (indirect); L (indirect); M (indirect); N (direct)]
	Value definition Defining value  Define the meaningfulness of clinical outcome measures [C (direct); E (indirect); F (direct)] Designing endpoints Provide input in the creation of endpoints that are relevant, meaningful, and functional [C (indirect); E (indirect); F (direct)]	Value definition Defining value  Define the meaningfulness of clinical outcome measures [G (indirect)] Designing endpoints Provide input in the creation of endpoints that are relevant, meaningful and functional [C (indirect); G (indirect)]	Value definition Defining value Define the meaningfulness of clinical outcome measures [J (indirect)]	Value definition Defining value  Define the meaningfulness of clinical outcome measures [L (indirect); M (direct); N (indirect)] Designing endpoints Provide input in the creation of endpoints that are relevant, meaningful and functional [C (indirect); L (indirect); M (direct); N (indirect)]
	Clinical trials Designing trials  Set clinically meaningful endpoints [B (direct); C (direct); D (indirect); E (direct); F (direct)]  Set patient inclusion/exclusion criteria for trial participation [A (direct); B (direct); C (direct); E (direct)] Providing data Participate in clinical trials [A (direct); B (direct); C (direct); E (direct)]	Clinical trials Designing trials  Set clinically meaningful endpoints [B (direct); C (direct); D (indirect); E (direct); F (direct)]  Set patient inclusion/exclusion criteria for trial participation [A (direct); B (direct); C (direct); E (direct)] Providing data Participate in clinical trials [A (direct); B (direct); C (direct); E (direct)]
Regulatory approval	Patient registries Providing data  Provide information through natural history registries [A (indirect); B (indirect); C (indirect); D (direct); E (indirect); F (indirect)]  Report on outcomes when receiving treatment [A (indirect); B (direct); E (direct)]  Participate in ongoing monitoring and data collection [A (indirect); B (direct); E (direct)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (indirect); B (direct); E (direct); F (indirect)]	Patient registries Providing data  Provide information through natural history registries [A (indirect); E (indirect); G (indirect); J (direct)]  Report on outcomes when receiving treatment [A (indirect); B (direct); E (direct); G (indirect); J (direct)]  Participate in ongoing monitoring and data collection [A (indirect); B (direct); E (direct); G (indirect); J (direct)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (indirect); B (direct); E (direct); F (indirect) G (indirect); J (direct)]	Patient registries Providing data  Provide information through natural history registries [A (indirect); J (direct)]  Report on outcomes when receiving treatment [A (indirect); J (direct]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (indirect); J (direct)]	Patient registries Providing data  Provide information through natural history registries [A (indirect); J (direct)]  Report on outcomes when receiving treatment [A (indirect); L (indirect); M (indirect); N (direct)]  Participate in ongoing monitoring and data collection [A (indirect); L (indirect); M (indirect); N (direct)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (indirect); L (indirect); M (indirect); N (direct)]
	Value definition Defining value Define the meaningfulness of clinical outcome measures [C (direct); E (indirect); F (direct)	Value definition Defining value Define the meaningfulness of clinical outcome measures [G (indirect)]	Value definition Defining value Define the meaningfulness of clinical outcome measures [J (indirect)]	Value definition Defining value Define the meaningfulness of clinical outcome measures [L (indirect); M (indirect); N (indirect)]
	Benefit–harm assessment Input into benefit–harm trade-off acceptability decisions  Provide information on tolerance [A (indirect); B (direct); C (indirect); E (direct); F (indirect)] Make final benefit–harm trade-off decision [F (direct)]	Benefit–harm assessment Input into benefit–harm trade-off acceptability decisions  Provide information on tolerance [A (indirect); B (direct); C (indirect); E (direct); F (indirect)] Make final benefit–harm trade-off decision [F (direct)]		Benefit–harm assessment Input into benefit–harm trade-off acceptability decisions  Provide information on tolerance [A (indirect); B (indirect); J (indirect); L (direct); M (direct); N (direct)] Make final benefit–harm trade-off decision [F (direct); L (direct)]
Post-marketing/real world studies	Patient registries Providing data  Provide information through natural history registries [A (direct), C (indirect); D (direct); E (indirect); F (indirect)]  Report on outcomes when receiving treatment [A (direct); B (direct); E (direct)]  Participate in ongoing monitoring and data collection [A (direct); B (direct); E (direct)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (direct); B (direct); E (direct); F (indirect)]	Patient registries Providing data  Provide information through natural history registries [A (indirect); E (indirect); G (indirect), J (direct)]  Report on outcomes when receiving treatment [A (direct); B (direct); E (direct); G (indirect), J (direct)]  Participate in ongoing monitoring and data collection [A (direct); B (direct); E (direct); G (indirect), J (direct)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (direct); B (direct); E (direct); F (indirect); G (indirect), J (direct)]	Patient registries Providing data  Provide information through natural history registries [A (indirect); J (direct)]  Report on outcomes when receiving treatment [A (indirect); J (direct]; K (indirect)]  Participate in ongoing monitoring and data collection [A (indirect); J (direct); K (indirect)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (indirect); J (direct); K (indirect)]	Patient registries Providing data  Provide information through natural history registries [A (indirect); J (direct)]  Report on outcomes when receiving treatment [A (indirect); L (indirect); M (indirect); N (indirect)]  Participate in ongoing monitoring and data collection [A (indirect); L (indirect); M (indirect); N (indirect)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (indirect); L (indirect); M (indirect); N (indirect)]
	Value definition Defining value  Define the meaningfulness of clinical outcome measures [A (direct); C (direct); E (indirect); F (direct)] Designing endpoints Provide input in the creation of endpoints that are relevant, meaningful and functional [A (direct); C (indirect); E (indirect); F (direct)]	Value definition Defining value  Define the meaningfulness of clinical outcome measures [G (indirect)] Designing endpoints Provide input in the creation of endpoints that are relevant, meaningful and functional [C (indirect); G (indirect)]	Value definition Defining value Define the meaningfulness of clinical outcome measures [J (indirect)]	Value definition Defining value  Define the meaningfulness of clinical outcome measures [L (indirect); M (indirect); N (indirect)] Designing endpoints Provide input in the creation of endpoints that are relevant, meaningful and functional [A (direct); C (indirect); L (indirect); M (direct); N (indirect)]
	Benefit–harm assessment Input into benefit–harm trade-off acceptability decisions Provide information on tolerance [A (direct); B (direct); C (indirect); E (direct); F (indirect)]	Benefit–harm assessment Input into benefit–harm trade-off acceptability decisions  Provide information on tolerance [A (indirect); B (direct); C (indirect); E (direct); F (indirect)] Make final benefit–harm trade-off decision [F (direct)]	Benefit–harm assessment Input into benefit–harm trade-off acceptability decisions Provide information on tolerance [F (direct); L (direct); K (indirect)]	Benefit–harm assessment Input into benefit–harm trade-off acceptability decisions Provide information on tolerance [A (direct); B (indirect); J (indirect); L (direct); M (direct); N (direct)]
Reimbursement decision-making	Patient registries Providing data  Provide information through natural history registries [A (direct), C (indirect); D (direct); E (indirect); F (indirect)]  Report on outcomes when receiving treatment [A (direct); B (direct); E (direct)]  Participate in ongoing monitoring and data collection [A (direct); B (direct); E (direct)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (direct); B (direct); E (direct); F (indirect)]	Patient registries Providing data  Provide information through natural history registries [A (direct); E (direct); G (indirect), J (direct)]  Report on outcomes when receiving treatment [A (direct); B (direct); E (direct); G (indirect), J (direct)]  Participate in ongoing monitoring and data collection [A (direct); B (direct); E (direct); G (indirect), J (direct)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (direct); B (direct); E (direct); F (indirect); G (indirect), J (direct)]	Patient registries Providing data  Provide information through natural history registries [A (indirect); J (direct)]  Report on outcomes when receiving treatment [A (indirect); J (direct]; K (indirect)]  Participate in ongoing monitoring and data collection [A (indirect); J (direct); K (indirect)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (indirect); J (direct); K (indirect)]	Patient registries Providing data  Provide information through natural history registries [A (indirect); J (direct)]  Report on outcomes when receiving treatment [A (indirect); L (direct); M (direct); N (direct)]  Participate in ongoing monitoring and data collection [A (indirect); L (direct); M (direct); N (direct)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (indirect); L (direct); M (direct); N (direct)]
	Value definition Defining value Define the meaningfulness of clinical outcome measures [A (direct); C (direct); E (indirect); F (direct)]	Value definition Defining value Define the meaningfulness of clinical outcome measures [G (indirect)]	Value definition Defining value Define the meaningfulness of clinical outcome measures [J (indirect)]	Value definition Defining value Define the meaningfulness of clinical outcome measures [L (indirect); M (indirect); N (indirect)]
	Benefit–harm assessment Input into benefit–harm trade-off acceptability decisions  Provide information on tolerance [A (direct); B (direct); C (indirect); E (direct); F (indirect)] Make final benefit–harm trade-off decision [F (direct)]	Benefit–harm assessment Input into benefit–harm trade-off acceptability decisions  Provide information on tolerance [A (indirect); B (direct); C (indirect); E (direct); F (indirect)] Make final benefit–harm trade-off decision [F (direct)]	Benefit–harm assessment Input into benefit–harm trade-off acceptability decisions Provide information on tolerance [F (direct); L (direct); K (indirect)]	Benefit–harm assessment Input into benefit–harm trade-off acceptability decisions  Provide information on tolerance [A (indirect); B (indirect); J (indirect); L (direct); M (direct); N (direct)] Make final benefit–harm trade-off decision [F (direct); L (direct)]
	Reimbursement process Provide information on the patient experience  Present individual cases, as well as data that is difficult to quantify, through testimonials and presentation to decision makers [A (direct); B (direct); E (direct), F (direct)] Participate in the decision-making process  Provide input in the creation of decision parameters [A (direct); B (direct); E (direct), F (direct)]  Participate on decision-making panels, providing input and clarifying the input from patient submissions [A (direct); B (direct); E (direct), F (direct)]  Accept when evidence of efficacy is insufficient [F (indirect)] Right to appeal  Present individual case when a negative funding decision has been made [A (direct); B (direct); E (direct), F (direct)] Add to submissions where information provided by the manufacturer was insufficient [A (direct); B (direct); E (direct), F (direct)]	Reimbursement process Provide information on the patient experience  Present individual cases, as well as data that is difficult to quantify, through testimonials and presentation to decision makers [A (direct); B (direct); E (direct), F (direct); G (direct); M (indirect)] Participate in the decision-making process  Provide input in the creation of decision parameters [A (direct); B (direct); E (direct), F (direct); G (direct); H (indirect); I (indirect)]  Participate on decision-making panels, providing input and clarifying the input from patient submissions[A (direct); B (direct); E (direct), F (direct); G (direct); H (indirect); I (indirect)]  Accept when evidence of efficacy is insufficient [F (indirect); H (indirect); I (indirect)] Right to appeal  Present individual case when a negative funding decision has been made[A (direct); B (direct); E (direct), F (direct); G (direct)] Add to submissions where information provided by the manufacturer was insufficient [A (direct); B (direct); E (direct), F (direct); G (direct)]	Reimbursement process Provide information on the patient experience  Present individual cases, as well as data that is difficult to quantify, through testimonials and presentation to decision makers [G (direct); H (indirect); J (direct); K (direct)] Participate in the decision-making process  Provide input in the creation of decision parameters [G (direct); H (indirect); J (direct); K (direct); M (direct); N (direct); O (direct)]  Participate on decision-making panels, providing input and clarifying the input from patient submissions [G (direct); H (indirect); J (direct); K (direct); M (direct); N (direct); O (indirect)] Accept when evidence of efficacy is insufficient [G (direct); H (indirect); J (direct); K (direct); M (direct); N (direct)]	Reimbursement process Provide information on the patient experience  Present individual cases, as well as data that is difficult to quantify, through testimonials and presentation to decision makers [A (direct); B (direct); E (direct); F (direct); G (direct); H (indirect); J (direct); K (direct); L (direct); M (indirect); N (direct); O (direct)] Participate in the decision-making process  Provide input in the creation of decision parameters [A (direct); B (direct); E (direct); F (direct); G (direct); H (indirect); J (direct); K (direct); L (direct); M (indirect); N (direct); O (direct)]  Participate on decision-making panels, providing input and clarifying the input from patient submissions [A (direct); B (direct); E (direct); F (direct); G (direct); H (indirect); J (direct); K (direct); L (direct); M (indirect); N (direct); O (direct)]  Accept when evidence of efficacy is insufficient [A (direct); B (direct); E (direct); F (direct); G (direct); H (indirect); J (direct); K (direct); L (direct); M (indirect); N (direct); O (direct)] Right to appeal  Present individual case when a negative funding decision has been made [A (direct); B (direct); E (direct); F (direct); G (direct); L (indirect); M (direct); N (direct)] Add to submissions where information provided by the manufacturer was insufficient [A (direct); B (direct); E (direct); F (direct); G (direct); L (indirect); M (direct); N (direct)]
	Managed access Providing information on the patient experience  Providing input into the design of a structured approach to collecting information on patient experiences [A (direct); B (direct); E (direct), F (direct); M (direct); N (direct)] Patient registries  Participate in registries as part of data collection for managed access plans (MAPs) [A (direct); B (direct); E (direct), F (direct); J (direct)] Stopping criteria Decide on stopping criteria with input from a specialist with relevant expertise [A (indirect); B (indirect); E (indirect); F (indirect); K (indirect); M (direct); N (direct)]	Managed access Providing information on the patient experience  Providing input into the design of a structured approach to collecting information on patient experiences [A (direct); B (direct); E (direct), F (direct); G (direct); K (indirect); L (direct); M (direct); N (direct)] Patient registries  Participate in registries as part of data collection for MAPs [A (direct); B (direct); E (direct), F (direct); G (direct); H (indirect); J (direct); K (indirect)] Stopping criteria Decide on stopping criteria with input from a specialist with relevant expertise [A (indirect); B (indirect); E (indirect); F (indirect); G (direct); H (indirect); K (indirect); L (direct); M (direct); N (direct)]	Managed access Providing information on the patient experience  Providing input into the design of a structured approach to collecting information on patient experiences [A (indirect); B (indirect); E (indirect), F (indirect); K (direct); L (direct); M (direct); N (direct)] Patient registries  Participate in registries as part of data collection for MAPs [A (indirect); B (indirect); E (indirect), F (indirect); H (indirect); J (direct); K (direct); L (direct); M (direct); N (direct)] Stopping criteria Decide on stopping criteria with input from a specialist with relevant expertise [A (indirect); B (indirect); E (indirect); F (indirect); H (indirect); K (indirect); L (direct); M (direct); N (direct)]	Managed access Providing information on the patient experience  Providing input into the design of a structured approach to collecting information on patient experiences [A (direct); B (direct); E (direct), F (direct); G (direct); K (indirect); L (direct); M (direct); N (direct)] Patient registries  Participate in registries as part of data collection for managed access plans (MAPs)  [A (direct); B (direct); E (direct), F (direct); G (direct); H (indirect) K (indirect); L (direct); M (direct); N (direct)] Stopping criteria Decide on stopping criteria with input from a specialist with relevant expertise [A (direct); B (direct); E (direct), F (direct); G (direct); H (indirect) K (indirect); L (direct); M (direct); N (direct)]
Introduced as insured service/ use in routine clinical practice	Patient registries Providing data  Report on outcomes when receiving treatment [A (direct); B (direct); E (direct); G (direct); L (indirect); M (indirect); N (indirect)]  Participate in ongoing monitoring and data collection [A (direct); B (direct); E (direct); G (direct); L (indirect); M (indirect); N (indirect)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (direct); B (direct); E (direct); F (indirect); G (direct); L (indirect); M (indirect); N (indirect)]	Patient registries Providing data  Provide information through natural history registries [A (direct); E (direct); G (indirect), J (direct)]  Report on outcomes when receiving treatment [A (direct); B (direct); E (direct); G (indirect), J (direct)]  Participate in ongoing monitoring and data collection [A (direct); B (direct); E (direct); G (indirect), J (direct)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (direct); B (direct); E (direct); F (indirect); G (indirect), J (direct)]	Patient registries Providing data  Provide information through natural history registries [A (indirect); J (direct)]  Report on outcomes when receiving treatment [A (indirect); J (direct]; K (direct)]  Participate in ongoing monitoring and data collection [A (indirect); J (direct); K (direct)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (indirect); J (direct); K (direct)]	Patient registries Providing data  Provide information through natural history registries [A (indirect); J (direct)]  Report on outcomes when receiving treatment [A (indirect); L (direct); M (direct); N (direct)]  Participate in ongoing monitoring and data collection [A (indirect); L (direct); M (direct); N (direct)]  Provide ‘subjective’ data, such as PROs and patient satisfaction [A (indirect); L (direct); M (direct); N (direct)]
		Value definition Defining value Define the meaningfulness of clinical outcome measures [J (direct)]	Value definition Defining value Define the meaningfulness of clinical outcome measures [J (indirect)]
	Managed access Providing information on the patient experience  Providing input into the design of a structured approach to collecting information on patient experiences [A (direct); B (direct); E (direct), F (direct); G (direct); J (direct); K (indirect); M (direct); N (direct)] Patient registries  Participate in registries as part of data collection for managed access plans (MAPs) [A (direct); B (direct); E (direct), F (direct); G (direct); J (direct); K (indirect); M (direct); N (direct)] Stopping criteria Decide on stopping criteria with input from a specialist with relevant expertise [A (direct); B (direct); E (direct), F (direct); G (direct); J (direct); K (indirect); M (direct); N (direct)]	Managed access Providing information on the patient experience  Providing input into the design of a structured approach to collecting information on patient experiences [A (direct); B (direct); E (direct), F (direct); G (direct); K (indirect); L (direct); M (direct); N (direct)] Patient registries  Participate in registries as part of data collection for MAPs [A (direct); B (direct); E (direct), F (direct); G (direct); H (indirect); J (direct); K (indirect)] Stopping criteria Decide on stopping criteria with input from a specialist with relevant expertise [A (direct); B (direct); E (direct); F (direct); G (direct); H (indirect); K (indirect); L (direct); M (direct); N (direct)]	Managed access Providing information on the patient experience  Providing input into the design of a structured approach to collecting information on patient experiences [A (indirect); B (indirect); E (indirect), F (indirect);G (direct); K (direct); L (direct); M (direct); N (direct)] Patient registries  Participate in registries as part of data collection for MAPs [A (indirect); B (indirect); E (indirect), F (indirect); G (direct); H (indirect); J (direct); K (direct); L (direct); M (direct); N (direct)] Stopping criteria Decide on stopping criteria with input from a specialist with relevant expertise [A (indirect); B (indirect); E (indirect); F (indirect); G (direct); H (indirect); K (indirect); L (direct); M (direct); N (direct)]