Quality assurance program for a hospital investigational-drug service.

The development and implementation of a quality-assurance (QA) program for a pharmacy-based investigational-drug service are described. The objective of the QA program was to assess the quality of the activities in the areas of drug acquisition, inventory control, availability of drug data sheets and dispensing guidelines, provision of a quarterly drug accountability report, and documentation of drug dispensing to patients and decentralized pharmacy areas. The audit criteria were based on hospital policies and procedures and federal regulations for the handling of investigational drugs. Audits of four randomly selected protocols are conducted quarterly by a pharmacist who is not affiliated with the investigational drug service. The results of the first two audits have identified several areas for improvement, including the need for additional pharmacy staff education regarding study protocols, the importance of maintaining complete and accurate drug accountability records by decentralized pharmacists, and the need to provide a centralized source of study protocol information. The QA program has enabled the investigational-drug service to establish and enforce the policies and procedures for the appropriate handling of investigational drugs in this institution.

Albumin utilization in a university hospital.

The inappropriate use of high-priced agents such as human serum albumin significantly contributes to the rising cost of medical care. A utilization review was conducted at the University of Michigan Hospital in order to identify the appropriateness of use of this agent. Criteria were developed and prescribing was retrospectively evaluated for 81 patients. Of the 935 units administered to these patients, 692 (74 percent) were judged to be inappropriate. This inappropriate use accounted for a projected annual expenditure of nearly $281,000. Interventions have previously demonstrated success in improving prescribing.

Development and funding of a pharmacy-based investigational drug service.

The development, implementation, and operation of a pharmacy-based investigational drug service (IDS) at a university medical center are described. Before the IDS was established, pharmacy participation in investigational drug research was limited to the preparation of novel dosage forms. Medication errors, improper storage and labeling, and inadequate inventories of investigational drugs were common problems. Stepped-up enforcement by FDA and the National Cancer Institute (NCI) of guidelines for investigational drug control prompted the formation of a multidisciplinary task force, which recommended that the department of pharmaceutical services expand its support of investigational drug studies to include inventory control, record keeping, and clinical services. The IDS is supported by both the hospital and the school of medicine and currently receives 36% of its funding from principal investigator grants and contracts. The IDS coordinates more than 100 study protocols and dispenses more than 4000 doses of investigational drugs annually. The IDS is staffed by 1.0 full-time equivalent (FTE) clinical pharmacist and 0.5 FTE technician. Inventory control and billing functions are performed by a departmental microcomputer system. The IDS has demonstrated a positive gross margin for each of its first two years of operation. Problems associated with the control and use of investigational drugs at this institution have been successfully corrected by the implementation of a pharmacy-based IDS.

Pimozide: use in Tourette's syndrome.

The orphan drug pimozide was recently approved for marketing in the U.S. for the treatment of Tourette's syndrome (TS). TS is characterized by recurrent, involuntary motor movements and vocal tics, and is believed to be due to neurochemical dysfunction. Pimozide's receptor selectivity differs from that of haloperidol, the standard agent used for TS. Clinical trials with pimozide demonstrate a positive response for many patients, although superiority over haloperidol has not been demonstrated in general. Pimozide causes annoying side effects in a large percentage of patients and may cause severe side effects (e.g., tardive dyskinesia, cardiovascular toxicity) with prolonged use and/or at higher doses. The long half-life of pimozide allows for once-daily dosing. Pimozide should be reserved for treatment of patients with TS who have not responded to haloperidol or who cannot tolerate haloperidol's adverse effects.

New drug evaluations amiloride (Midamor, Merck, Sharp and Dohme).

Amiloride is a potassium-sparing diuretic that is pharmacologically similar to triamterene. It has been widely used abroad for several years, alone and in combination with hydrochlorothiazide. As a potassium-sparing agent, amiloride appears to be approximately as effective as triamterene and spironolactone and to have a longer duration of action than triamterene, allowing once daily dosing. The diuretic effect of amiloride is mild, as are all agents that act at distal tubular sites. Amiloride appears to have an antihypertensive effect approximating that of the thiazides and spironolactone-an advantage over triamterene, which is devoid of antihypertensive effects. Amiloride will probably be most useful as a potassium-sparing agent in combination with the thiazide and loop diuretics. It should be kept in mind, however, that many patients on thiazide diuretics do not need supplemental potassium or potassium-sparing agents if they have no other complicating factors, such as digitalis therapy. When hypokalemia causes symptoms, a potassium-sparing agent have advantages over oral potassium supplements in patient tolerance and compliance. Because of the possibility of tumorigenicity and estrogenic side effects, spironolactone's popularity has been decreasing in recent years. Amiloride will probably be a strong competitor of triamterene and spironolactone because of its longer duration of action than triamterene and, from early indications (cf. ticrynafen), more benign side effects than spironolactone. The drug should be used with great caution, if at all, in patients with impaired renal function, however. The benefits of amiloride will have to be weighed against the cost of the drug in individual patients.