The consequences of diarrhea occurring during chemotherapy for colorectal cancer: a retrospective study.

PURPOSE: Diarrhea is one of the dose-limiting toxicities associated with chemotherapy agents in treatment regimens for colorectal cancer. The objectives of this study were to analyze the impact of all grades of diarrhea on clinical decisions for patients receiving treatment for colorectal cancer by characterizing the diarrhea that occurred, quantifying changes in chemotherapy treatment, identifying methods to treat diarrhea, and determining the economic impact. Patients and Methods. We retrospectively reviewed the treatment of 100 consecutive patients with colorectal cancer who experienced diarrhea during the course of chemotherapy. The diarrhea was documented in the progress notes and graded according to National Cancer Institute Common Toxicity Criteria. Changes in chemotherapy treatment and resource utilization associated with diarrhea were recorded. RESULTS: The 100 patients received 673 chemotherapy cycles, of which 45% +/- 2% were associated with diarrhea. Approximately 52% of patients experienced diarrhea of grades 3 or 4, and 56 patients underwent 66 modifications in their chemotherapy treatment, such as dose reductions (22), delays in therapy (8), discontinuations of therapy (15), or multiple changes (11). Thirty-seven patients consumed resources beyond oral antidiarrheals to control diarrhea: 14 patients received emergency outpatient treatment, 23 patients were hospitalized, 21 patients received intravenous fluids, and one death due to dehydration was reported. Discussion and Conclusion. Diarrhea was a significant consequence of colorectal chemotherapy, with the majority of patients experiencing grades 3 or 4 diarrhea and 56% of all patients also modifying their chemotherapy treatment. Even mild diarrhea of grades 1 and 2 was associated with changes in treatment in 11% of patients; thus, diarrhea of all grades should be recognized and treated appropriately to maintain full-dose chemotherapy.

The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory.

BACKGROUND: Fatigue is a major disease and treatment burden for cancer patients. Several scales have been created to measure fatigue, but many are long and difficult for very ill patients to complete, or they are not easy to translate for non-English speaking patients. The Brief Fatigue Inventory was developed for the rapid assessment of fatigue severity for use in both clinical screening and clinical trials. METHODS: The study enrolled 305 consecutive, consenting adult inpatients and outpatients with cancer who could understand and complete the self-report measures used in the study. The same instruments also were administered to 290 community-dwelling adults to obtain a comparison sample. Research staff completed a form that indicated the primary site and stage of the cancer, rated the Eastern Cooperative Oncology Group performance status of the patient, described the characteristics of the pain, and described the current pain treatment being provided to the patients. RESULTS: The BFI was shown to be an internally stable (reliable) measure that tapped a single dimension, best interpreted as severity of fatigue. It correlated highly with similar fatigue measures. Greater than 98% of patients were able to complete it. A range of scores defining severe fatigue was identified. CONCLUSIONS: The BFI is a reliable instrument that allows for the rapid assessment of fatigue level in cancer patients and identifies those patients with severe fatigue.

Cost-effectiveness of interferon-alpha and conventional chemotherapy in chronic myelogenous leukemia.

OBJECTIVE: To compare the cost-effectiveness of interferon-alpha with that of hydroxyurea as initial therapy for patients with chronic myelogenous leukemia (CML) in the chronic phase. DESIGN: A decision analysis and Markov model that described the natural history of the therapeutic process. The Markov model contained two treatment arms (interferon-alpha and hydroxyurea) and eight states of health (complete hematologic remission with cytogenetic response, complete hematologic remission without cytogenetic response, partial hematologic remission, chronic phase without hematologic remission, accelerated phase, blast crisis, bone marrow transplantation, and death). Probabilities, costs, and utilities were obtained from published clinical studies and clinical investigators. MEASUREMENT: Quality-adjusted years of life saved and costs and qualities discounted at 5% per year. SETTING: University medical centers in North America and Europe. PATIENTS: Meta-analysis of results from patients studied in clinical trials. RESULTS: The model's predictions of median survival (69 months with interferon-alpha therapy and 58 months with hydroxyurea therapy) were derived from data in the recent literature. In patients 50 years of age, interferon-alpha improved life expectancy over hydroxyurea by approximately 18 months. The marginal cost-effectiveness of interferon-alpha (incremental discounted cost of interferon-alpha compared with that of conventional therapy) was $34800 per quality-adjusted year of life saved. The model was sensitive to the monthly cost of interferon-alpha therapy (if the cost of interferon-alpha is reduced by one third, the cost-effectiveness becomes $19300 per quality-adjusted year of life saved) but was not particularly sensitive to the costs associated with blast crisis or bone marrow transplantation. The other significant variable was quality of life during therapy with interferon-alpha; when this measure was varied from 70% to 100% of the quality of life during hydroxyurea therapy, cost-effectiveness changed from $123200 to $25620 per quality-adjusted year of life saved. When the quality of life associated with interferon-alpha was less than 62% of the quality of life associated with hydroxyurea, the discounted quality-adjusted life expectancy with interferon-alpha was less than that with hydroxyurea. CONCLUSION: Compared with hydroxyurea, interferon-alpha is, in most clinical scenarios, a cost-effective initial therapy for patients with chronic-phase CML who can tolerate the drug.

Impact of clinical trial protocols on patient care systems at the University of Texas M.D. Anderson Cancer Center.

Clinical trial protocols represent a significant component of the research program at the University of Texas M.D. Anderson Cancer Center. Currently, there are nearly 800 active protocols using more than 150 investigational drugs. Sponsors of these trials include the National Cancer Institute, numerous pharmaceutical companies, and a variety of other funding sources. Because of our large patient base, however, routine participation in cooperative groups is limited. The impact of clinical trial protocols on patient care systems is a growing concern that is addressed primarily by the Surveillance Committee at M.D. Anderson. Like many institutional review boards, this committee reviews all protocols and must grant approval before the activation of any clinical trial. The issues of medical ethics, including a risk-benefit assessment for research subjects, equitable patient selection, safeguards for economically disadvantaged populations, and the general requirements for informed consent, also fall under the purview of this board. For any comprehensive cancer center to succeed, it must have strong research programs that enhance treatment options for patients. The crisis in financing health care significantly threatens the viability of cancer research. Reimbursement for the related costs of individuals participating in clinical trials has become a battle ground for third-party payers. The resulting economic risk is shared by health care providers and patients. As a consequence, many cancer centers, including M.D. Anderson, have initiated an economic-impact analysis for protocols as a component of the review process. This analysis includes an estimation of the patient care costs compared to the funding allocated to support the research. Future research will include pharmacoeconomic analysis and other ways to relate the costs and outcomes of treatment protocols. In the interim, we must monitor reimbursement trends for patients enrolled in clinical trials closely and amend the informed consent process to include a discussion of potential economic risk or hardship to patients if insurance claims are denied. Cancer care providers, third-party payers, the federal government, and society at large must work together to address the funding of cancer research and patient care.

Strategic management of biotechnology agents.

The use of biologic response modifiers to demonstrate a value-driven approach to strategic management by pharmacists is described. To participate in decisions on the use of technology in their institutions, pharmacists must practice strategic management. This process includes environmental scanning, analysis of clinical and pharmacoeconomic data, and development of clinical management approaches. It is ideal for analyzing biologic response modifiers such as filgrastim and sargramostim. Emphasis must be placed on maximizing the fit among the products, the institution, and the health care environment. Pharmacists will find plentiful opportunities for clinical management with biotechnology agents. Practitioners who specialize in determining the total cost of care by using pharmacoeconomic methods are needed, as are practitioners trained to monitor the complicated biotechnology agents. Also, the institution needs to forecast accurately the impact of emerging biotechnology agents. If pharmacists can develop and control clinical, pharmacoeconomic, and reimbursement information databases for biotechnology agents, the pharmacy profession will be in a strong position to meet the challenges of biotechnology and realize the inherent opportunities.

Strategic planning for the colony-stimulating factors.

The rapid development and emergence into the marketplace of therapeutic and diagnostic biotechnology products pose a considerable challenge to pharmacists, particularly in light of economic strictures wrought by changes in the health care field. At the same time, the pharmacy profession is moving to a position of greater involvement and responsibility in the clinical management of drug therapy. These changes mandate that pharmacists become strategic thinkers, capable of designing and implementing plans that can integrate biotechnology products into their institutions' practices in a way that both enhances patient care and maintains or promotes financial stability. A strategic plan model incorporating the components of environmental scanning and strategy formulation, implementation, and analysis can be applied to the recombinant colony-stimulating factors.

Drug usage guidelines, Part 3: assessment of acceptance of the program.

The Drug Usage Guidelines (DUG) program, as perceived by the members of the P & T Committee and by physicians who had prepared and submitted DUGs, was demonstrated to be an effective method for evaluating drugs for formulary inclusion. The majority of P & T members felt that the DUG program had strengthened the drug review process without being too tedious or preventing the addition of valuable drugs to the formulary. Sixty-eight percent of physicians who had submitted a DUG expressed the opinion that it served as a vehicle for providing educational information on rational therapeutics. A majority of respondents stated that they would recommend the DUG program to other hospitals.

Drug usage guidelines, Part 2: Analysis of program outcome.

The effect of integrating a Drug Usage Guidelines (DUG) program with a hospital formulary system was analyzed. Significant changes were observed in both the number of requests submitted to the P & T Committee and the number of drugs added to the formulary after implementation of the DUG program. Failure to follow the DUG submission protocol, particularly with respect to the requirement for supportive clinical data from the primary literature, led to delayed consideration and eventual withdrawal of several highly promoted drug products. The initial involvement of physicians in the planning and implementation of the DUG program has been an important factor in the continued success of the program.

Strengthening the formulary system by implementing a drug usage guidelines program.

The development and implementation of a Drug Usage Guidelines (DUG) program in a 1,200-bed, federal teaching hospital are described. The program was designed to promote effective formulary control through established procedures for the review and evaluation of drugs submitted to the Pharmacy and Therapeutics (P & T) Committee for addition to the formulary. The procedures required the submission of the DUG and an oral presentation to the Committee prior to any final vote on the request. Anticipated potential benefits of the DUG program are to: (1) stimulate rational drug therapy, (2) provide reliable drug information to the professional staff in a usable format, (3) promote a thorough evaluation of therapeutic agents before approving for formulary inclusion, and (4) provide physician-generated guidelines for use as criteria in drug utilization review audits.

Influencing drug use through prescribing restrictions.

The effect of several drug restriction policies on benzodiazepine and cephalosporin use was evaluated in a large federal hospital. Computerized drug-use data were examined for the 10-year period from 1972 through 1981. The five major types of drug restrictions implemented were the: (1) requirement that all diazepam prescriptions be countersigned by the chief of staff, (2) deletion of cephalothin sodium from the formulary, (3) required countersignature by a physician from the infectious disease service for all cefazolin sodium prescriptions, (4) requirement that justification accompany all cefazolin sodium prescriptions after the countersignature requirement was lifted, and (5) amendment of the countersignature requirement for diazepam with a series of designated exceptions. All of the restrictions resulted in a decrease in the number of dosage units dispensed; however, the required countersignature by the chief of staff and deletion from the formulary were the most effective in restricting drug use. The effect of the restriction policies appears to be related to the influence or power of the restriction enforcer and the perceived importance of the restriction, as well as the relative difficulty of drug acquisition by the prescriber. Formulary deletion, countersignature requirements, or restricted use to a service or physician are action plans that may alter the use rates of drugs.

Internal standards: rationale for use in a drug utilization review program.

The comparison of drug usage data gathered from different institutions would be easier if standardized criteria were employed. There are, however, major difficulties encountered in gaining approval of such criteria from different physician groups. To facilitate the criteria approval process, "internal standards" were developed. These internal standards reflected the acceptable deviations from the standardized criteria, hence, permitting flexibility for innovation in drug therapy. A retrospective drug utilization review was conducted in two hospitals. The internal standards assigned were very similar to the 0 percent-100 percent standards recommended by InterQual except for the criteria on monitoring parameters and duration of therapy. It would appear from these preliminary results that the assignment of internal standards enhances the use of standardized criteria which, in turn, will allow comparisons of data.