methods David G Greenhouse 7 021

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					David G Greenhouse

7.021 Section B

Meeting #2

Out of Class Exercise 2


Organization of Study

       We designed a computer simulation of the movement of a population through

various disease states related to ESH, atrial fibrillation, and their treatment. By assigning

each disease state a cost and a utility we can determine the total number of discounted

quality adjusted life years (QALY’s) accumulated by the population. We analyze two

treatment strategies: radioiodine ablation of the thyroid and long-term observation (a wait

and see strategy).

       Using Data 4.0 (Tree Age Software, Inc., Williamstown, MA) we created a

Markov decision tree and implemented a Monte Carlo simulation with a yearly time step.

A schematic of Markov state diagrams for both treatments is shown below. Patients

moved between disease states at probabilities determined by the literature. Costs were

accumulated from a societal perspective given public financial data. Each year’s costs

and benefits were discounted 3% to account for the decreased value of distant costs (e.g.-

inflation). Each simulation ended once all patients had entered the dead clinical state. A

sensitivity analysis was then performed on all costs and transition probabilities in order to

determine the stability of the decision.
Base Case Demographics

       Male and female populations were considered separately. Initially 10,000 patients

were divided into preliminary disease states given their prevalence in the Framingham

data. These patients all begin at age 60 due to the lack of data regarding ESH in patients

younger than 60 years. We also considered all patients to already have ESH confirmed

by third generation TSH assay level less than 0.1 mU/L on two separate occasions at least

two months apart.

Transition Probabilities

       The initial probability of having repeatedly high TSH assays was estimated from

the Wickham survey among others. These values range from 0.2-11.8%, but is likely

between 0.6-1.2%. Disease prevalence data for atrial fibrillation for the general

community were taken from the Framingham study. In order to determine the probability

of developing atrial fibrillation from the ESH disease state we utilized the data of Sawin,

et al and Scheibner, et al. Scheibner’s data showed a 12.3% chance of developing atrial

fibrillation (n=613), a marked increase over the 2.3% chance in the rest of the population

(n=22,300). We assumed the chance of developing atrial fibrillation to be uniformly

distributed over the lifespan of the population. Unfortunately, this study defined ESH as

those with a TSH <0.4 mU/L. As well, they did not require a repeated positive result.

Nevertheless, this suggests that the actual rate of development of atrial fibrillation in

those with ESH is higher than 12.3% since many “normal” patients without ESH (and

most likely a lower incidence of atrial fibrillation) were included in the population. The

probability of overt hyperthyroidism following diagnosis of TSH was taken from
Wiersinga as 5% per year when untreated. Age related all-cause mortalities were taken

from the CDC’s National Vital Statistics Report, 2002.

Treatments, Costs, and Efficacy

        For all costs, we took a societal perspective. Therefore, whenever possible, we

compiled average medicare costs for treatments and physician consultations. For

radioiodine, we assumed an average treatment of 12mCi and recommend a standardized

dose regimen based on palpated thyroid size (Kok SW, et al). We assume 85% of

subclinically hyperthyroid patients treated with iodine will no longer be hyperthyroid

after one year. The remaining 15% will require re-administration of treatment (after

which no patients are still hyperthyroid). 15% of those treated once and 20% of those

treated twice will become hypothyroid from too high a dosage. The costs of treatment for

hypothyroid patients included treatment with levathyroxine at $340 per year (Osby’s,

2000). Patients with atrial fibrillation incur a cost of $1,458 per year using the data of

GB Lumber, et al.


        When available quality of life weights were taken from Tengs, et al’s

compilation: “One thousand health-related quality-of-life estimates”. For the ESH

untreated state with no symptoms we assigned it a QALY of 1.0, since by definition there

is no loss of quality of life. For the inconvenience of radioiodine therapy we assigned

that year a QALY of 0.8. For mixed disease states, such as ESH with atrial fibrillation

we assigned the lower QALY score.

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