Outcome measures

Many of the questions listed above address issues within the clinical episode, but the evaluation of the longer-term value or benefit of a diagnostic test is more complex. Longterm costs and benefits, as in management of a chronic condition such as diabetes, may be influenced by other (confounding) factors. The complexity depends on the rela- 

---

Acetyl-i-carnitine (4) is marketed in Italy for dementia as of this writing it is also in Phase III clinical trials in the United States and Europe. In a double-blind, placebo-controUed clinical trial over a one-year period involving 130 patients with clinically diagnosed AD, a slower rate of deterioration in 13 of the 14 outcome measures was observed in the dmg-treated group (28). Earfler smaller scale pilot studies in demented patients had also shown some improvement of various behavioral and cognitive functions (29). 

Mode of evaluation Cost measurement Outcome measurement... 

Cost-benefit analysis Cost-effectiveness analysis Cost-consequences analysis Cost-utility analysis Cost-offset analysis Comprehensive Comprehensive Comprehensive Comprehensive Comprehensive Monetary valuation of outcomes One outcome only Multiple outcomes measured Summary utility score of outcomes No outcomes measured... 

Outcome measurement is not discussed further in this chapter, hut it should he emphasized that some distinctive contributions could be made by economics. These include the development of summary unidimensional measures (discussed in the cost-utility section earlier), and benefit valuation in monetary terms (with its attendant difficulties, even though valuation methods are breaking new ground). However, acceptable (and potentially insightful) economic evaluations can be conducted without resorting to utility or benefit measurement. Cost-effectiveness and cost-consequences approaches have a lot to offer, building on outcome measures which will be more familiar to non-economist researchers in the field. It is for this reason that cost-effectiveness and cost-consequences analyses, linked to drug trials, are the most likely to be used over the next few years. 

Cost-utility analysis is similar to cost-efFectiveness analysis in approach, but uses utility as the outcome measure. The utility value is a measure that combines preferences for and values of the overall effect of an intervention on survival, physical and mental health, and social function. Utility is combined with estimates of length of life to provide an assessment of quality-adjusted life years (QALYs). As in cost-efFectiveness analysis, incremental cost-utility ratios are calculated to estimate the cost of producing one extra QALY. 

Cramer SC, Koroshetz WJ, Einklestein SR The case for modality-specific outcome measures in clinical trials of stroke recovery-promoting agents. Stroke 2007 38 1393-1395. 

All clinical trials should have a pre-specified research question, which may be stated in the form of a primary hypothesis (or possibly a few primary hypotheses). An objective outcome measure or measures should also be clearly identified, such as the results of a biochemical test or the score on a validated scale. This allows statistical tests to be applied in order to assess the likelihood that any differences in response between treatment groups resulted from the active treatment and were not due to chance. 

With investigations of phytochemicals and functional foods, the outcome measure is generally going to be a biomarker of disease, such as serum cholesterol level as a marker of heart disease risk, or indicators of bone turnover as markers of osteoporosis risk. Alternatively, markers of exposure may also indicate the benefit from a functional food by demonstrating bioavailability, such as increased serum levels of vitamins or carotenoids. Some components will be measurable in both ways. For instance, effects of a folic acid-fortified food could be measured via decrease in plasma homocysteine levels, or increase in red blood cell folate. 

This example shows not only that it is difficult to develop outcome measures, but that measuring outcomes may be rendered more difficult and complicated by other factors. On the one hand, spurious effects may be found, caused by factors other than regulatory functions. On the other hand, even when regulation does work, detection of the desired outcomes and their impact may be difficult. 

Even though outcome measures may fail to detect the intended effects, this does not automatically mean that regulation is ineffective it may be that this particular regulatory mechanism, although necessary, is unable to produce the intended outcomes alone. The challenge is to identify factors that will complement the regulatory mechanism in order to achieve the desired outcomes. 

Examining the inspectors workloads will also help to establish reasons for the success or failure of the inspection process. EHiring their inspection of pharmaceutical establishments, inspectors may learn of the presence of unregistered products, counterfeit products, etc. Quantitative information on these and other issues is valuable as an outcome measure. 

Each of the countries operates a quality analysis system for post-marketing control of drug quality, albeit with vast differences in capacity. Data on the outcome measure for drug quality— the number of dmg samples that failed quality tests compared with the total number of samples collected— are available in all the countries, except the Netherlands. Failure rates are high in some countries, e.g. Tunisia and Uganda. In Australia, high failure rates are found for herbal and other complementary products, compared with prescription dmgs. Empirical data on sanctions applied in such instances are not available. 

Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004 8 R204-R212. 

The success of therapy is measured by the degree to which the care plan decreases the pretreatment deterioration rate, preserves the patients functioning, and treats psychiatric and behavioral symptoms. The primary outcome measure is thus subjective information from the patient and the caregiver, although the MMSE can be a helpful tool for monitoring changes in the severity of illness. There are no physical examination or laboratory parameters that are used to evaluate the success of therapy. 

A randomized, double-blind, placebo-controlled trial evaluating the use of a monophasic OC containing 30 meg ethinyl estradiol and 3 mg drospirenone, a progesterone with anti-androgenic effects, showed improvement in the treatment arm compared with placebo.31 In particular, appetite, food cravings, and acne improved. However, active treatment was not associated with a statistically significant improvement in the overall outcome measure, the Calendar of Premenstrual Experiences (COPE) scale, perhaps because of the small sample size (n = 82). 

TABLE 46-3. Expected Outcome Measures for Select Menstrual Bleeding Disorders8 10,11,15 1e 20 22 33 36... 

Although many clinical studies have been performed evaluating antibiotics for ABRS, no randomized, double-blind, placebo-controlled studies have used pre- and posttreatment sinus aspirate cultures as an outcome measure. Despite this, antibiotics appear to resolve symptoms more quickly and reduce failure rates and complications compared with no treatment.35-37 Since diagnosis usually is based on clinical presentation and not sinus aspirate cultures, clinicians must attempt to differentiate ABRS from viral rhinosinusitis. Therefore, it is important to limit antibiotic use to cases where infection is unlikely to resolve without causing prolonged disease patients with mild to moderate symptoms that persist for 10 days or worsen over 5 to 7 days and patients with severe symptoms,31,34... 

Recent advances in the treatment of cancer of the colon and rectum now offer the potential to improve patient survival, but for many patients, improved disease- and progression-free survival represent equally important therapeutic outcomes. In the absence of the ability of a specific treatment to demonstrate improved survival, important outcome measures should include the effects of the treatment on patient symptoms, daily activities, performance status, and other quality-of-life indicators. Individualized patient care to balance the risks associated with treatment with the benefits of a specific treatment regimen is necessary to optimize patient outcomes. 

Most treatment-resistant depressed patients have received inadequate therapy. Issues to be considered in patients who have not responded to treatment include the following (1) Is the diagnosis correct (2) Does the patient have a psychotic depression (3) Has the patient received an adequate dose and duration of treatment (4) Do adverse effects preclude adequate dosing (5) Has the patient been compliant with the prescribed regimen (6) Was treatment outcome measured adequately (7) Is there a coexisting or preexisting medical or psychiatric disorder (8) Was a stepwise approach to treatment used (9) Are there other factors that interfere with treatment ... 

---