Health technology assessment.

The developing role and use of diagnostic imaging continue to emerge as disease management paradigms are refined and clinical guidelines are employed more often. Health technology assessment, HTA (also known as health care technology assessment), is fundamentally a form of policy research. By formulating effective HTA, the short- and long-term effects of health care technology are studied in a systematic and multidisciplinary way. The fundamental aim of all HTA is to assist those individuals and organizations who stand to benefit from a new health technology (patients), those who will apply the technology (providers), and those who will pay for it (payers) to make better decisions about the technology they utilize by supplying information that is of a high scientific standard and population-based. Effective HTA is especially useful to health care providers, payers, professional groups in health care, manufacturers, political decision-makers and the general public or consumers of health care technology because it represents a process through which effective technology can be identified and ineffective technology can be understood in the context of its limitations. HTA is a multidisciplinary undertaking requiring combined expertise in clinical medicine, epidemiology, biostatistics, bioengineering, health economics, administration, psychology, sociology, ethics and legal science. Additionally, the experiences and opinions of health technology users and consumers of health care (especially patient advocacy groups) are needed to form an overall accurate understanding of the technology under review.

Utility evaluations for Markov states of lung cancer for PET-based disease management.

BACKGROUND: Utilities for the health outcomes states (Markov states) of non-small cell lung carcinoma (NSCLC) should be measured to evaluate management options for patients because patients are key participants in the process of care, and their assessment of diagnostic and therapeutic value in the options presented to them ultimately impacts their net health outcomes. This investigation sought to measure utilities for stage-dependent outcomes states of NSCLC. METHODS: Persons (n = 23) with suspected NSCLC based on physical findings and computed tomography completed a short utilities survey. Utility valuations were obtained according to severity of morbidity and varied considerably. Respondents rated these health states according to accuracy measures for 18flurodeoxyglucose (18FDG) positron emission tomography (PET) imaging and medastinoscopy. RESULTS: The results demonstrate that stage-dependent morbidity is an important consideration for patients with NSCLC and should be included in any decision analysis regarding the evaluation or treatment of NSCLC. Respondents valued the quality of information obtained from non-invasive PET and invasive mediastinoscopy comparably. The utilities obtained from this investigation are useful in clinical decision-making based on Markov processes because they provide an initial estimation of utility assessment for 18FDG-based diagnostic evaluation of lung cancer. CONCLUSIONS: Consequently, these utilities will be useful in future decision analyses that require patient preference in the assignment of the evaluation of decision options (branches).

The willingness to pay for positron emission tomography (PET): evaluation of suspected lung cancer using contingent valuation.

BACKGROUND: In this study, contingent valuation is used to estimate the willingness-to-pay (WTP) for positron emission tomography (PET) imaging by patients with suspected benign or malignant lung disease. METHODS: Patients (n = 87) undergoing thoracic computed tomography were surveyed for their WTP for PET for the evaluation of lung disease in lieu of further testing. Patients were provided background PET information and a two-page self-administered questionnaire. The survey queried basic demographic information, perceived risk of malignancy, and perceived life expectancy given a diagnosis of malignancy. RESULTS: Patients with increased perception of risk were willing to pay more than those with lower perceived risk. Patients who were self-payers for their health insurance indicated a lower WTP than those who did not pay any out-of-pocket insurance premiums. CONCLUSIONS: Individuals are willing to pay additional out-of-pocket costs for diagnostic imaging to reduce their perception of risk and improve their quality of life.

Decreased serum E-selectin concentration after 89Sr-chloride therapy for metastatic prostate cancer bone pain.

UNLABELLED: Palliative systemic radionuclide therapy with 89Sr-chloride is a useful intervention for patients with bone pain from metastatic prostatic cancer. Although this radionuclide is highly effective, its mechanism of action remains unresolved. This investigation sought to determine whether systemic radionuclide therapy decreases the production of cell adhesion molecules (E-selectins) that participate in the metastatic process. METHODS: Sera were collected from 25 men with metastatic (stage IV) prostate carcinoma who received 89Sr-chloride palliative therapy and from 10 age-matched healthy volunteers. The serum concentration of E-selectin was quantified by an enzyme-linked immunosorbent assay. Sera from 5 patients who received 2 courses of radionuclide therapy were also included in the analysis. RESULTS: A 2.8-fold decrease in serum E-selectin concentration occurred within 2 mo of radionuclide therapy (P < 0.0001). At 10 mo, however, the concentration increased to a mean (+/- SD) of 151.2 +/- 51.3 ng/mL, surpassing the baseline concentration. This pattern coincided with symptomatic improvement and subsequent health status deterioration. For patients who received 2 courses of radionuclide therapy, a second fall in serum E-selectin concentration followed the second radionuclide treatment. CONCLUSION: A significant decrease in serum E-selectin concentration was observed after systemic radionuclide therapy. This finding suggests that expression of cell adhesion molecules, an important determinant of metastatic progression, may be inhibited by 89Sr-chloride.

Variation in oncologic opinion regarding management of metastatic bone pain with systemic radionuclide therapy.

UNLABELLED: The objective of this study was to determine whether there is consistency of opinion regarding the management of metastatic bone disease pain among medical oncologists who are given the option of using systemic radionuclide therapy (89Sr, 153Sm). METHODS: One hundred board-certified medical oncologists were given a brief clinical summary of three patients with metastatic cancer. Management options included oral, parenteral and transdermal delivery forms of opioid analgesics; external beam irradiation; and systemic radionuclide therapy. The oncologists rated, in whole numbers from 1 (most appropriate) to 10 (least appropriate), their opinions on the appropriateness of each proposed intervention for each patient. RESULTS: Systemic radionuclide therapy was perceived consistently as having low appropriateness for palliation of metastatic bony pain compared with opioid analgesics. A slight increase in appropriateness for systemic therapy was indicated for the patient with widespread metastatic disease, who, on the basis of literature reports, was unlikely to benefit from such therapy. The oncologists rated the appropriateness of systemic therapy as low in the patient with limited early disease, in which the literature indicates the greatest benefit will be derived from such intervention. CONCLUSION: Referring oncologists perceive the appropriateness of systemic radionuclide therapy as low. Their perception of its appropriateness increases with extent of disease. As a result, this palliative option is underutilized or used in less-than-optimal disease settings.

Recombinant human growth hormone for AIDS-associated wasting.

OBJECTIVE: To review the current literature regarding the role of recombinant human growth hormone (rhGH) in the treatment of AIDS-associated wasting and to briefly describe alternative therapies. DATA SOURCES: A literature search was performed on MEDLINE and AIDSLINE for the period from January 1985 through September 1997. Key words used in the search strategy were growth hormone, human immunodeficiency virus, acquired immune deficiency syndrome, wasting, and weight gain. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in this review. Abstracts were included only when they were judged to add critical information. Thereafter, the inclusion was restricted to English-language articles and abstracts on clinical trials and human studies in AIDS-associated wasting. DATA SYNTHESIS: Body wasting, characterized by an involuntary loss of body cell mass, is a well-recognized feature of many chronic diseases, including infection with HIV AIDS-associated wasting is a metabolic disorder characterized by weight loss, depletion of lean body mass (LBM), and preservation of body fat, leading to muscle weakness and organ failure. rhGH has been approved by the Food and Drug Administration for use in treating AIDS-associated wasting. The adverse event profile is similar to that of other rhGH products. The recommended dosage of rhGH is 4-6 mg administered by subcutaneous injection daily. It offers a more expensive alternative to appetite stimulants such as megestrol acetate and dronabinol. CONCLUSIONS: Trials with rhGH on the control of wasting in patients with AIDS have been encouraging, but with limited conclusive evidence of sustainable positive outcomes. Studies demonstrate that rhGH increases LBM and decrease adipose tissue, but how these translate into long-term outcomes such as decreased hospitalization, morbidity, and mortality has yet to be determined. A formal health economic assessment is needed to properly determine the impact of rhGH on the healthcare system.

Quantitation of biochemical markers of bone resorption following strontium-89-chloride therapy for metastatic prostatic carcinoma.

UNLABELLED: The urinary production of pyridinium collagen cross-links, pyridinoline (PYD) and deoxypyridinoline (DPD), has been correlated to increased bone resorption in patients with neoplasms. This study investigated the production of these compounds in patients with metastatic prostate carcinoma who received palliative treatment that did and did not include 89Sr-chloride therapy. METHODS: Urinary production of PYD and DPD was measured by high-performance liquid chromatography and natural flucrescence detection methods. The urine from several age-matched groups of patients was examined for these compounds including healthy controls (n = 20), patients with early-stage (Stage A-B) prostate carcinoma (n = 8), patients with metastatic prostate carcinoma treated with conventional analgesic and radiotherapeutic palliation (n = 20), patients with metastatic disease who underwent 89Sr-chloride therapy (n = 20) and patients with mild Paget's disease (n = 5). Patients were also monitored for urinary PYD and DPD production for a 6-mo interval after a palliative intervention. RESULTS: Elevated PYD and DPD (p < 0.05) concentrations were measured in patients with metastatic and nonmetastatic prostate cancer and Paget's disease. The urinary production of these compounds remained unchanged for 6 mo after 89Sr-chloride therapy for symptomatic osseous metastases. However, the patients who did not undergo 89Sr-chloride therapy exhibited a two-fold increase in PYD and a four-fold increase in DPD above controls during the interval. CONCLUSION: PYD and DPD are sensitive and specific bone resorption markers which demonstrate a slowing of bone resorption after palliative 89Sr-chloride therapy in patients with bone metastases.

Serum PICP as a bone formation marker in 89Sr and external beam radiotherapy of prostatic bony metastases.

The clinical management of skeletal metastatic disease is problematic because of the difficulty in treating and accurately monitoring therapy impact and disease progression. This investigation measured serum procollagen type I C-terminal peptide (PICP) concentrations as a semi-quantitative index of bone turnover in patients with metastatic prostatic adenocarcinoma before and following palliative 89Sr chloride therapy. 10 patients with early stage (stage A2, B1 and B2) biopsy-confirmed prostatic adenocarcinoma were investigated (n = 10). Two groups of 10 patients each (n = 10 per group) with advanced (stage D) metastatic prostatic adenocarcinoma who had previously undergone hormonal manipulation were also investigated. One group of patients with scintigraphically documented metastatic bone disease received additional irradiation for new symptomatic bone metastases, whereas the other group received 89Sr chloride therapy. A radioimmunoassay for PICP was used to measure serum concentrations of patients in each of these groups as well as positive and negative controls. The concentration of serum PICP rose from 649 +/- 279 before treatment with external beam radiotherapy to 927 +/- 157 ng ml-1 4 months after therapy (p < 0.05). However, the results demonstrated a four-fold decrease (p < 0.001) in serum PICP in clinical responders to 89Sr chloride therapy versus baseline 4 months after the completion of treatment. The clinical non-responders demonstrated no significant change in PICP concentrations during that interval. This may be due to an increase in untreated bony metastases in the non-89Sr treated group. Although a relatively small representative group of patients was studied, these data demonstrate that serum PICP concentration correlates with clinical response to 89Sr chloride therapy. This objective laboratory technique may be useful for monitoring and predicting the need for 89Sr chloride therapy and optimizing palliative care. It may also be extremely useful in predicting a therapeutic response to such intervention.

Increased superoxide anion production in polymorphonuclear leucocytes on exposure to isobutyl-2-cyanoacrylate.

Alkyl-2-cyanoacrylates have been employed in a variety of surgical procedures, although the pathophysiological basis for their cytotoxicity has not been resolved. Previous reports indicated that leucocytes infiltrate the site of cyanoacrylate application in situ. Consequently, human polymorphonuclear leucocytes were treated with 0-200 mM cyanoacrylate isobutyl-2- and superoxide anion radical production, lactate dehydrogenase release, and intracellular reduced glutathione content were quantitated following this treatment. In addition, some cells were also treated with 0-20 mM ascorbic acid before exposure to the adhesive. Pretreatment with ascorbic acid resulted in a statistically significant decrease in superoxide production (up to 111%), decrease in lactate dehydrogenase release (up to 26.4%) and a like increase in glutathione content (up to 26.6%). These results indicated that the cytotoxic properties of isobutyl-2-cyanoacrylate were diminished in a dose-dependent manner with addition of ascorbic acid, a free radical trapping agent. Moreover, isobutyl-2-cyanoacrylate appeared to increase specifically the production of superoxide anion. These findings suggested that the cytotoxicity of this class of adhesives may be associated with the formation of reactive oxygen intermediates.