The pharmacoeconomics of high-cost biotechnology products.

Biotechnology products have created therapy options in areas that have been historically limited. These improvements in patient care have resulted in a reappraisal of the emphasis placed on product acquisition costs and a movement toward evaluating the impact of the product on the entire health care system. Strategic planning for biotechnology products allows pharmacists to partner with the medical staff and financial/administrative representatives of the institution to measure clinical outcomes, estimate cost and revenue impact, document utilization, and promote cost-effective use of these new therapies to generate the maximum benefit for dollars expended.

Managing high cost and biotech drugs: two institutions' perspectives.

A proactive and multidisciplinary approach is used at The University of Texas MD Anderson Cancer Center to forecast the effect of new biotechnology and other high-cost agents prior to their commercial availability. Protocols, practice guidelines, and drug-use policies are developed to promote cost-effective use of these agents. To promote optimal utilization, two pharmacoeconomic strategies are used: cost reduction and drug performance. An economic impact analysis is performed on pending drug protocols, which includes hospital cost, patient billing, and estimates of insurance reimbursement denial risk. The management of biotechnology drug usage at the University of Pittsburgh Medical Center is through the drug advisory program (DAP). DAP is an organized, multidisciplinary program comprising numerous drug usage review functions including drug information, therapeutic evaluation and modification, drug morbidity and surveillance, and an investigational drug service. The objective of DAP is therapeutic efficiency, which has as its key elements efficacy, low toxicity, and low cost. The actual work of DAP takes place via multiple subcommittees and task forces whose recommendations are forwarded to the P & T Committee. These multidisciplinary groups ensure the involvement of the appropriate specialists in therapeutic decisions and, therefore, successful implementation of the recommendations.

Formulary decision making in a specialty hospital: effective management of potent and costly drug therapies.

Substantial progress has been made in the treatment of cancer in the past few decades. Complex drug therapy regimens, supportive-care therapies, and therapeutic complications--namely, infection--have made clinical management challenging, however. In this exclusive Hospital Formulary interview, Michael Keating, MD, and William Dana, PharmD, Chairman and Secretary, respectively, of the University of Texas M.D. Anderson Cancer Center's P & T Committee, discuss successful methods of maintaining an effective formulary in a cancer center. Although efficacy and toxicity of therapy remain the primary considerations when evaluating drugs, with a formulary weighted with cancer chemotherapeutic agents, antibiotics, and other supportive intravenous formulations, cost is also critical. These health professionals describe how they balance the issues associated with rational, yet cost-effective drug therapy.

Ifosfamide and mesna.

The chemistry, pharmacology, pharmacokinetics, and adverse effects of ifosfamide and mesna are described separately, followed by a discussion of the adverse effects of concurrent ifosfamide and mesna, the clinical spectrum of ifosfamide, and the dosage and administration of the two drugs. Ifosfamide, an active analogue of cyclophosphamide, differs from other direct alkylating substances in that it requires biotransformation in the liver before it can exert its alkylating effects. The bioavailability of ifosfamide after oral administration exceeds 95%. The adverse effects of ifosfamide include hematologic, urinary tract, GI tract, and CNS toxicity. Mesna is a thiol compound designed to function as a regional detoxificant of urotoxic oxazaphosphorine cytostatics such as ifosfamide. The drug is rapidly oxidized in the plasma to its dimeric form, dimesna, one third of which is converted back to mesna by glutathione reductase. The mean total urinary availability of mesna administered orally is 76%. Mesna may produce gastrointestinal and allergic reactions. The adverse effects of concurrent ifosfamide and mesna include urinary tract and renal toxicity. Although current FDA-approved labeling is limited to refractory germ cell testicular cancer, ifosfamide has also shown efficacy in the treatment of lymphoma, lung cancer, and sarcomas. Optimum dosage and scheduling remain to be determined; studies suggest that a fractionated dosage schedule provides antineoplastic activity with tolerable toxicity. Ifosfamide, used in combination with mesna for uroprotection, provides a useful therapeutic option for the management of patients with testicular cancer, soft tissue sarcomas, or high-grade malignant lymphomas.

Ethinyl estradiol and medroxyprogesterone acetate in patients with epithelial ovarian carcinoma: a phase II study.

Patients with ovarian carcinoma refractory to chemotherapy received a sequential combination of ethinyl estradiol and medroxyprogesterone acetate in two dose regimens. There was no difference in therapeutic activity of the two dose regimens. Of 65 patients, nine (14%) responded to treatment and 13 (20%) had stable disease. Vascular complications occurred in three patients; hemiplegia developed in one of those. Nine patients had significant nausea and vomiting, and one experienced severe depression that required treatment withdrawal. The sequential and combined use of ethinyl estradiol and medroxyprogesterone acetate may provide an alternative treatment for certain patients with ovarian carcinoma that does not respond to optimum chemotherapy. Additional studies are required to determine if synergism exists between this treatment and other modalities of therapy. Further investigation is required into the vascular disorders that complicate therapy to determine whether appropriate preventive measures are possible.

Genotoxic classification of anticancer drugs.

The effects of bacterial DNA excision repair on the mutagenic and lethal actions of 17 injectable anticancer drugs have been used to classify them into three levels of potential risk to medical personnel who are involved in their preparation and administration.

Risk of handling injectable antineoplastic agents.

Uptake of mutagenic substances by persons handling injectable antineoplastic agents was studied, and various methods of preventing such exposure were evaluated. Six persons who prepared i.v. admixtures individually collected their urine in 24-hour batches during several eight-day study periods; each prepared from 12 to 90 admixtures per working day during each period. I.V. personnel prepared admixtures in both horizontal laminar-flow hoods and vertical-flow biological-safety cabinets, and using gloves and masks. Three pharmacy personnel who did not handle any drugs served as controls. Urine was concentrated (each 24-hour sample was concentrated to about 1 ml), and the Salmonella/mammalian microsome mutagenicity test (Ames test) was used to detect mutagenic activity in the urine concentrates. Mutagenicity was observed in the urine of all personnel during periods when they prepared antineoplastic admixtures in horizontal laminar-flow hoods, both when using no protection and while wearing gloves or masks. When admixtures were prepared in the vertical-flow biological safety cabinet by personnel wearing gloves, no urine mutagenicity was detected. The control group showed no urine mutagenicity. Protective intervention methods should be used by all persons handling antineoplastic agents. Guidelines for handling these drugs are presented.

Human serum albumin usage in a comprehensive cancer center.

During 1977, M.D. Anderson Hospital and Tumor Institute used 270,575 g of human serum albumin (HSA) at a patient cost of $1.1 million. For a 1-month period in early 1978, a survey of HSA usage was conducted in the 440-bed hospital. Patients who were started on albumin during the study period were included and monitored for the duration of their therapy. The largest groups of patients receiving albumin were those with gynecological tumors (30%) and gastrointestinal tumors (16%). Two-thirds of all patients receiving HSA were also receiving intravenous hyperalimentation (IVH); 80% of all HSA used was given to IVH patients. Although the IVH patients received a smaller daily dose of HSA, the average length of their therapy was about three times longer than that of the non-IVH patients. The mean total dose for the IVH patients was 344 g as compared to 180 g for non-IVH patients. For all patients, the mean total dose of HSA was 289 g at a patient cost of $1212. Of the patients, 66% had an initial serum albumin level determined before therapy was begun, 43% had a serum albumin level run at the termination of therapy, 16% had neither, and 28% had only one serum albumin level during their HSA therapy. Ninety percent of the patients had at least one period of 4 days or longer without a serum albumin level being obtained.

Drug information services in an oncology institution.

Information requests received over a 14-month period in the drug information service of an oncology hospital were reviewed. Requests were classified as to the nature of the question, category of requestor and geographical distribution of both questions and requestors. Inquiries were tabulated as either oncology-related or nononcology and further divided into one of 12 information categoreis. Those questions concerning investigational chemotherapy and unproven cancer remedies were tabulated. An average of 104 requests monthly were received. Prescribing practitioners accounted for 47.7% of all inquirers. Overall, 39.4% of total requests were oncology-related. The majority (72%) of total requests originated within the institution. The greatest number of requests (17.7%) were of a general review nature. The second greatest number (14.3%) were efficacy-related questions which solicited an opinion as to the appropriateness of drug use. Methods need to be developed for measuring the impact of drug information services on prescribing habits.