7/16/2009. Cost-benefit, QALYs and the Value of a Statistical Life

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1 7/16/29 Cost-benefit, QALYs and the Value of a Statistical Life Alan McKenzie, Bristol The benefits of many developments in radiotherapy may be obvious for instance, replacing hand planning by computer treatment planning. However, in some cases, it is not so clear that the benefits outweigh the detriments Reduce frequency of quality control checks (eg linac output checks) Introduce routine in-vivo dosimetry for all or most patients at the beginning of their treatment Reduce the cost of the service and free up staff for other work Potential for delay in discovering any errors more severe clinical consequences Treatment error may be detected before harm done Cost of service increases and staff have less time to develop new technology Use IGRT cone-beam CT scanning on every fraction throughout treatment In order to make choices we need to express costs and benefits in terms of the same units Increased patient survival through more accurate targeting Extra time on linac and possible radiation carcinogenesis Linac and staff time Patient survival Treatment morbidity (quality of life) 1

2 7/16/29 It costs 2 per hour to run a linac What value do you put on a human life? For each human life lost in a train crash, society is willing to pay between 1 million and 1 million to avoid such an accident. This is called the Value of a Statistical Life (VOSL). This is the currency that we use to optimise the frequency of checking. The VOSL (value of a statistical human life) lies in the range 1 million to 1 million, but with a narrower range of 2 million to 4 million being applied for most routine purposes. Quality Adjusted Life Years (QALYs) - utility values Healthy person = 1. Home dialysis =.64 Severe angina =.5 We take the very lowest point in this band, 1million. Moderate radiotherapy bowel injury =.47 Death =. 2

3 7/16/29 NICE will fund drugs that cost less than 3, per QALY gained. NICE will fund drugs that cost less than 3, per QALY gained. Note that, at this rate, an extra 3 years of goodquality life resulting from such treatment will cost in the order of 1 million, which is the VOSL! Hence, Society is willing to pay up to 3, per QALY and up to 1 million per life saved How quality of life and QALYs may be derived from the side effects of radiation (N) Prostate 43% (64.8 Gy) 64% (7.2 Gy) 73% (75.6 Gy) Rectal N 13% Gade 2 toxicity for 81 Gy N TD5 (v=1/3) = 88 Gy (Emami 1991 and others) N The key assumption is that the probability of a dose resulting in a given level of damage is correlated with the debilitating effect of the dose in a given patient N

4 7/16/ Rectal toxicity (g =.53) New definition: Detriment is defined as: Detriment = g x N N Detriment Utility value (for surviving patients) = 1 Detriment = 1 (g x N) N Detriment Utility value = Utility value (for surviving patients) years QALYs (assuming survivors live 1 years) Utility value Note that QALYs are proportional to if N and quality of life is ignored years QALYs (assuming survivors live 1 years) Utility value Typical range of treatment dose years Utility value QALYs (assuming survivors live 1 years)

5 7/16/29 Linac Quality Control Some of the following examples are taken from IPEM Report 92 Is it cost-effective to reduce the frequency of linac output checks from weekly to monthly? We assume that the probability of a typical 3.5% excursion is 1% per linear-accelerator-year. We do not include the effects of overdosing in calculating the effects of reducing checking frequencies. This includes excursions resulting from human error. We consider only parameter excursions leading to underdosing and tumour recurrence, and assume that the probability of such an excursion is half the total, ie.5% per annum for a given linear accelerator Treatment model Treatment model Assume, at any one time, radical patient throughput: 5 patients in first week of treatment 5 patients in second week of treatment 5 patients in third week of treatment 5 patients in last week of treatment Assume that each linac treats 26 new radical patients per year 5

6 7/16/29 1 Percent tumour control probability We assume a simple radiobiological model 5 γ 5 =.2 typical 3.5% excursion Output calibration Treatment model Radiobiological model Number of patients with tumour recurrence if there is a parameter excursion Expected number of patients at incident rate of.5% p.a. Weekly calibration % p.a. Monthly calibration D 5 Expected increase of patients with tumour recurrence in moving from weekly to monthly calibration We take 11 years of life from each patient who has a local recurrence of tumour Hence, moving from weekly to monthly calibrations costs.13 x 11 =.14 QALYs Society would be willing to pay up to.14 x 3, = 42 to avoid this! weekly monthly Reducing linac output calibrations from weekly to monthly Saving = 3 x 2 minutes } } } = 1 hour per month = 12 hours per year = 12 x 2 = 2,4 per year In this case, the low chance of loss of life is outweighed by the costs of preventing loss of life. However, the analysis does not account for the remote possibility of a catastrophic error 42 Value of benefit linac time 2,4 Cost of detriment + catastrophic error? Value of benefit linac time 2,4 Cost of detriment 6

7 7/16/29 Is routine in-vivo dosimetry on every patient justified in terms of resources? Total 3964 courses Error Number of errors detected by IVD Number per million courses Wrong photon energy Incorrect MU Incorrect compensating filter Total Incorrect calculation and missing compensating filter Klein et al. Errors in radiation oncology: A study in pathways and dosimetric impact Vol Up to 17 Up to 4288 Total Up to 26 Up to 665 Assume that 5 radical patients per year are saved from underdosing by in-vivo dosimetry in a six-linac centre. Assume an average increase of 1% per radical patient saved from underdosing. Therefore, in-vivo dosimetry contributes 5 x 1% x 11.5 years = 5.8 QALYs per year Therefore, society would be willing to pay 3, per QALY x 5.8 QALYs = 174, per year 7

8 7/16/29 6 hours 6 hours In-vivo dosimetry is cost effective! Total cost of in-vivo dosimetry in 6-linac centre = 6 x 6 = 36 linac hours 6 hours = 72, per year 6 hours linac time 72, 174, 6 hours 6 hours Cost of detriment Value of benefit STV PTV CTV How can you use QALYs to justify IGRT cone-beam CT scanning on every fraction when treating errant prostates? Inter-fractionial motion - both prostate and bony anatomy move relative to the room and the PTV Inter-fractionial motion bothanatomy prostate move and bony Both prostate and -bony anatomyrelative move relative to theand room to the room theand PTVthe PTV 8

9 7/16/29 Inter-fractionial motion bothanatomy prostate move and bony Both prostate and -bony anatomyrelative move relative to theand room to the room theand PTVthe PTV Inter-fractionial motion bothanatomy prostate move and bony Both prostate and -bony anatomyrelative move relative to theand room to the room theand PTVthe PTV Joe Ideally, we should like to plot the position of prostate, not bony anatomy Anterior 2.5 cm Monday Tuesday 1..5 Wednesday Right Thursday Left Inter-fractionial Both prostate motion and -bony bothanatomy prostate move and bony anatomyrelative move relative to the room to theand room theand PTVthe PTV -2.5 Friday Posterior Joe Joe Anterior 2.5 cm Monday Average position of prostate Tuesday Wednesday Thursday Friday Right Re-centre the beam delivery on the average position of the prostate Anterior 2.5 cm Monday Tuesday Left Wednesday Thursday Right Left Posterior Friday Posterior 9

10 7/16/29 Joe Monday Tuesday Calculate the standard deviation of prostate position Anterior 2.5 cm Joe Monday Tuesday Question how bad must the random daily error be before you need to do a daily cone-beam scan and re-centre every day? Anterior 2.5 cm σ sup-inf = 1 cm.5 σ sup-inf = 1 cm.5 Wednesday Thursday Right Left -1. σ L-R =.4 cm -1.5 Wednesday Thursday Right Left -1. σ L-R =.4 cm Friday -2.5 Posterior Friday -2.5 Posterior treated volume underdose CTV CTV treated volume treated volume underdose CTV CTV underdose 1

11 7/16/29 CTV When the prostate is not re-centred with daily CBCT scans, there is a rind of underdosing with particularly errant prostates. Daily random error, σ CBCT / cm loss.5% 1% 3% 2% 4% CTV PTV margin, m / cm Daily random error, σ CBCT / cm 2.5 4% loss 3% 1. 2%.5 1%.5% CTV PTV margin, m / cm So, when the standard deviation of the daily position of the prostate is 1cm (and the treatment margin is 1cm), the benefit of daily scanning and re-centring is 2% treated volume Will daily scanning and re-centring also reduce N? % dose 1% CTV rectum If we do not scan and re-centre every day, random daily changes in position will blur the boundary but, even when large changes are averaged over the patient population, there is no change in N, to the first order. 11

12 7/16/29 Scanning throughout scanning first week CBCT scan first few fractions only 14 years local control recurrence 2½ years loss = 2% 11½ years 14 years We assign a value of.7 for the utility value of a life of a patient cured of prostate cancer, ie 1 year of life =.7 QALYs. This is conservative life may be better! QALYs lost per patient through loss of local control when scanning first few fractions only = 2% x 11.5 years x.7 =.16 QALYs on average Scanning throughout scanning first week Radiation carcinogenesis Scanning throughout scanning first week Hence, benefit of scanning errant prostate patients (1cm SD, 1 cm margin) throughout treatment =.16 QALYs on average. Society would be willing to pay 3, x.16 = 4,8 for this benefit. 4,8 (errant prostates) Value of benefit linac time Cost of detriment Scanning throughout scanning first week CBCT scan throughout treatment.75% chance of radiation induced cancer 7 years 7 years local control recurrence 2½ years 11½ years Effective dose with M2 collimator = 1 msv per prostate scan 3 scans = 3 msv.75% chance of cancer induction for 7-year old man 14 years QALYs lost per patient through radiation carcinogenesis =.75% x 7 years x.7 =.4 QALYs 12

13 7/16/29 Scanning throughout scanning first week CBCT scan throughout treatment.75% chance of radiation induced cancer 7 years 7 years local control Radiation carcinogenesis 1,2 Scanning throughout scanning first week recurrence 2½ years 11½ years 14 years Society would be willing to pay 3, x.4 = 1,2 to avoid this. 4,8 (errant prostates) Value of benefit linac time Cost of detriment Radiation carcinogenesis 1,2 Scanning throughout scanning first week CBCT scanning on every fraction 1 minutes per scan, 3 fractions 5 hours at 2 per hour = 1, for CBCT 4,8 (errant prostates) Value of benefit linac time 1, Cost of detriment 4,8 Value of benefit Radiation carcinogenesis linac time 1, Cost of detriment 1,2 Scanning throughout scanning first week 2,2 Summary for cone-beam CT scanning A methodology has been presented for deciding when it is justifiable to scan and re-centre on every fraction. It relies on quantifying benefit and detriment in terms of cost of QALYs. The transparency of the methodology means that it can be updated as improved data become available (such as rates of radiation carcinogenesis). It may be applied equitably to all patients. 13

14 7/16/29 Conclusions Cost-benefit analysis can be used to underpin hard decisions in radiotherapy QALYs for a given activity may be calculated from, N and probability of radiation carcinogenesis Society is willing to pay up to 3, per QALY (which is approximately equal to 1 million per life) Other quantities in the benefit-detriment equation may also be expressed in terms of money, for example, linac time and staff costs It is more difficult to quantify the effects on staff, patients and the general public of a catastrophic error 14