Table 2.

Analysing the health economic Cauliflower Value Toolbox by its essential florets.

Domain	Floret	Definition	Outcome
Population & Disease (yellow in Figure 6)	Central/Root	Epidemiology data by age, gender, at-risk groups & management data.	Basic information for developing a natural disease model with current management impact.
Impact (red in Figure 6)	(1) Vaccine efficacy	Relative reduction in disease/infection incidence rate in the vaccinated group compared with an unvaccinated group.	Obtained through randomised clinical trials.
	(2) Effectiveness (impact) + herd protection	Measured under real-life conditions using case-control techniques or impact studies.	Comparing vaccinated with unvaccinated individuals (historic or not; isolated or not).
	(3) QoC	QoC in hospital care to be measured through bed-day management and people management.	Data should be compared between epidemic periods pre- versus post-vaccination introduction using an impacted summary score.
	(4) Portfolio management	Model-based approach that integrates natural disease history and management among target groups with optimisation analysis by identifying objective functions and specific constraints such as time, budget, logistics for combining different vaccines.	Portfolio management integrates multiple vaccines sequentially over a fixed period of time and budget while achieving maximum health gain.
	(5) Carbon footprint	Total carbon production using vaccination versus no vaccination as an important aspect of societal durability and sustainability of the environment.	Vaccination and reduced vaccine dosing impact carbon footprint in health care compared with no vaccination.
Subject (blue in Figure 6)	(1) Vaccinated subject	QALY to identify how much a disease may impact the utility preference of a subject in different health states.	Allows comparison across different diseases (using a general health-related quality of life instrument with domains common across many disease areas).
	(2) Caregiver	Healthcare professionals: overwork, sick leave, absenteeism, QoL. Informal caregivers: financial due to absenteeism from work and expenses related to providing informal care (out-of-pocket). QoL impact and well-being level should also be assessed.	Healthcare professionals: physicians and nurses may deliver better work and more professional care with fewer errors and better job satisfaction. Informal caregivers: family and friends may be affected both financially and in terms of QoL.
	(3) Employer	Reduction in absenteeism on the work floor will benefit the output of the enterprise. May pay less social security contribution for employees.	Number of days being absent from work because of caring for sick family members or because of being sick themselves as an employee.
	(4) Third party payer	Insured people are vaccinated. Their risk for getting the disease is lower and the need for costly medical care is lowered.	Financial benefit because the risk for hospitalisation is reduced by promoting and using vaccination.
	(5) Society	The disease takes away the benefit a healthy population normally provides (healthy workforce, schools, etc.).	Overall benefit considered from different angles/perspectives (direct, indirect, out of pocket, insurance, etc.).
Cost (green in Figure 6)	(1) Direct medical cost	Cost related to resource use for disease treatment (medical visit, laboratory test, medication, hospitalisation, specific intervention). Important to specify the perspective from which the cost is considered (reimbursement, third party, budget holder, patient [out-of-pocket], and society).	An important direct cost driver is hospitalisation to be specified by type (general ward, intensive care, other).
	(2) Non-medical andnon-healthcare cost	Cost that is not medically related to the disease but is a consequence of the disease like loss in income or production loss. Transport costs.	Other expenses than medical cost due to an episode of illness. They might be paid out of pocket over and above their healthcare expenses or lose income due to time off work.
	(3) BIM and BOM	BIM provides budget estimates of the likely impact of the new intervention. Vaccines always impose a high initial investment with cost offset spread over a long period of time. BOM is a modelling exercise that combines different interventions to achieve an objective function or a goal.	BIM identifies the health care budget change over time before and after the introduction of the new intervention. Three scenarios are possible: maintained budget increase after the introduction, budget neutral, savings because of high cost offset. BOM tries to define how to maximise health gain through a combination of new interventions while working under specific constraints, such as fixed budgets.
	(4) Macro-economic	This approach aims at estimating the broad economic consequences (i.e., beyond the sick person or care giver) of illnesses. It is a top-down approach of economic assessment.	Investing in vaccines means investing in human capital which is a foundation for economic growth. The impact of ill health on the economy goes beyond the number of workdays lost. For governments and donors, the choice of investing in health offers an important economic return expressed in GDP improvement.
	(5) Return on investment	This approach aims at estimating the vaccine investment on better tax payments over time because of maintained healthy conditions.	For governments and donors, the choice of investing in health offers an important economic return particularly in taxes.

QoC, quality of care; QoL, quality of life; QALY, quality-adjusted life-year; BIM, budget impact modelling; BOM, budget optimisation modelling; GDP: gross domestic product