Nonsteroidal Anti Inflammatory Drug NSAIDInduced Ulcer

Organic Health Protocol

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Consider the example of a 60-year-old man who is treated for his osteoarthritis with 375 mg of naproxen (Naprosen) bid. Because of his epigastric pain and nausea, the patient undergoes an esophagogastroduodenoscopy, which reveals a nonbleeding gastric ulcer with a clear ulcer base. His physician now wonders whether the naproxen should be replaced by a cyclooxygenase-2-selective inhibitor (COX-2), such as 100 mg celecoxib (Celebrex) bid or tid.

As an alternative to COX-2, the physician also considers treatment with a proton pump inhibitor (PPI), such as 20 mg of rabeprazole (Aciphex) once daily or bid. Which treatment option should be given preference?

Figure 2-1 depicts a decision tree to illustrate the current scenario. The initial decision between a COX-2 and a PPI is depicted by the first fork on the left side of the tree and symbolized by the open square at the first branching point. For the time being, the cost numbers in the lower right corner of each box should be ignored; we will deal with them later. The decision in favor of a COX-2 is followed by two chance events, symbolized by the open circle at the next branching point following the COX-2 decision. The patient may fare well on COX-2 and no other events or costs will ensue, or the patient will fail COX-2 treatment, redevelop his ulcer, and require a switch from COX-2 to PPI treatment added to a regular NSAID, such as naproxen. The branches leading off the chance node are assigned the two probability values (p) of .9 and .1. In general, all probabilities emanating from a chance node need to add up to 1.0. The NSAID plus PPI outcome is followed by yet another set of two probabilities. The patient may stay free of recurrent ulcerations on the NSAID plus PPI combination, and drug cost alone will be encountered with a .9 probability, or the patient may develop ulcer complications. The occurrence of future complications under NSAID plus PPI treatment in this patient, given his present ulcer, is given an overall p value of .1. Lastly, three possible complications are considered: pain, hospital admission, and death, with the three respective p values of .9, .09, and .01. The time frame of the analysis is restricted to one year.

A decision tree provides the means to describe the natural disease history and the possible occurrence of future events in terms of a flow diagram. The flow runs from the left to the right side of the tree and ends in a set of final events without further progression. In the tree of Figure 2-1, all boxes indicating final events have been shaded with a light gray. To calculate the tree outcome, the final events need to be described in terms of some commensurable values, the most commonly used descriptor being money. Frequently, however, the events can also be described in terms of other health parameters, such as healthy or pain free days, hospital days, or number of deaths, as long as the same unit of measurement is used to describe all the different outcomes. The physician estimated that episodes of pain would cost overall $500 per year. Similarly, the physician estimated that one hospital admission per year for ulcer complication would cost on the average $3,000. Death was equated with the average annual income in the United States. Lastly the drug costs associated with NSAID plus PPI treatment or COX-2 treatment was estimated based on pharmacy listings.

The tree outcome is calculated from right to left. The cost values of the final outcomes are multiplied by their probability of occurrence and added. The final fork on the right, for example, yields:

This process is called averaging out, because it calculates the average expected outcome of a chance fork. It is repeated again at the next fork to the left. For illustrative purposes, however, the drug costs that are still incurred in patients who experience ulcer complications have been left out. Rather than $1,020, the correct value of the box should be listed as $1,020 + $1,800 = $2,820, and the expected value of the next chance fork is actually:

This value also corresponds to the general expected value of PPI, as opposed to COX-2 treatment at the initial decision fork. Rather than redraw this part of the decision tree twice following the box labeled PPI, the detailed tree was executed only once and the expected value was then transferred to the initial PPI box. The identity of the two event boxes is symbolized by their double outline. The process

COX-2

-$632

PPI

10% switch $1,902

drug costs alone $1,200

drug costs alone $1,200

NSAID + PPI

10% switch $1,902

drug costs alone $1,800

with complications 9C 10% $1,020

pain

hospital

death

$30,000

FIGURE 2-1 Decision tree for management of NSAID-induced peptic ulcer. COX-2 = cyclooxygenase-2-receptor antagonist; NSAID = nonsteroidal anti-inflammatory drug; PPI = proton pump inhibitor.

of averaging out is thus carried out from right to left until all boxes have been assigned a value. The first box on the left contains the cost difference of the COX-2 minus PPI treatment strategy. A cheaper COX-2 treatment translates into a negative value for the overall tree. Accordingly, in this patient with active peptic ulcer, preference should be given to the COX-2 treatment strategy.

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