Therapeutic substitution in the health maintenance organization outpatient environment.

Health maintenance organizations (HMO) are growing in number as a cost-effective way of providing health care. In some, stringent formulary management policies including programs authorizing therapeutic substitution are practiced. Under this concept a drug that has been previously determined to be therapeutically equivalent to a second drug, even though it is not chemically equivalent to the prescribed drug, is automatically dispensed without contacting the prescriber. This study was undertaken to learn the extent and conditions under which therapeutic substitution is being practiced in the HMO setting. A survey was sent to all HMO in the U.S. inquiring into the operation of the pharmacy services. Specific focus was on the operation of the formulary and the policies and procedures being followed. The main goal was to learn how many programs authorize therapeutic substitution, what drugs are allowed, and what procedures are followed once the substitution is made. Of the 481 surveys sent out, 192 (40 percent) usable responses were received. Results indicate that 30.5 percent of HMO pharmacy plans allow therapeutic substitution. These programs were most likely to be of the staff-model or the group-model and least likely to be of the independent practice association type. HMO with an inhouse pharmacy more frequently had policies allowing therapeutic substitution than those using outside pharmacy services.

Accuracy of serum gentamicin concentration predictions generated by a personal-computer software system.

Predictions of serum gentamicin concentration and half-life, using a personal-computer software system (SIMKIN [simulated kinetics]), were compared for accuracy as increasing amounts of patient-specific data were supplied to the computer. Data for a two-year period were collected for patients of a hospital's pharmacokinetic consultation service; the study group included adults who had at least one serum concentration for which time of last gentamicin dose was recorded. Input variables were age, weight, height, sex, serum creatinine concentration, concomitant drugs and diseases, gentamicin dosage, time of infusion, dosing interval, number of doses on each regimen, and time and reported value of all serum gentamicin concentrations. Individualized dosing regimens were calculated on the basis of literature estimates, and half-life and serum concentrations were then estimated for these regimens and compared with actual values. One or two measured serum concentrations were then added to the input data. The computer-estimated half-lives (obtained from single-point or two-point analysis in different dosage intervals) were compared with the half-lives determined from actual serum concentration data. Gentamicin serum concentrations were similarly compared. The computer's ability to predict subsequent serum concentrations improved in sequence for literature-averaged prediction and single-point and multipoint analysis. Accuracy of predicting whether peak concentrations were therapeutic or subtherapeutic and whether trough concentrations were toxic also improved as more patient-specific data were input. SIMKIN appropriately evaluated demographic and laboratory data and adequately predicted gentamicin half-lives and serum concentrations.

Improving pharmacy and therapeutics committee operations.

A panel discussion of various aspects of the operations of pharmacy and therapeutics (P & T) committees is presented. Pharmacy and therapeutics committee operations in various types and sizes of hospitals are described. Ways of stimulating physicians' interest in P & T committee activities, difficult problems faced, scope of issues dealt with by P & T committees, functions of P & T subcommittees, the value of drug information from pharmaceutical representatives, and the influence of research funds from the pharmaceutical industry on committee decisions are discussed. Panel members also present their views on therapeutic alternates, FDA-nonapproved use of drugs, and counter-detailing. Finally, suggestions for improving P & T drug evaluations, cost-containment issues, and the authority of P & T committees are discussed. A well-prepared agenda, good educational material, active members, and strong leadership are important for successful P & T committee operations.

Therapeutic substitution: has its time arrived?

Therapeutic substitution refers to substitution by the dispenser of a drug product that is not chemically identical but is therapeutically equivalent to the product prescribed, pursuant to guidelines established by the hospital P & T Committee. Until recently, the extent to which this concept has been adopted by hospitals across the country was unknown. Late in 1980, we conducted a nationwide survey of hospital pharmacies to learn more about therapeutic substitution. This paper reviews some of the issues involved, some of the findings of our study, and the pros and cons of therapeutic interchange. It also provides an update as to some of the recent changes that are occurring in therapeutic substitution procedures.

Antibiotic restriction in hospitals associated with medical schools.

Restriction of antibiotic use in 112 hospitals that are primary teaching facilities for medical schools was studied by mail questionnaire to pharmacy directors and infectious disease physicians. Questions involved whether use of certain antipseudomonal penicillins, aminoglycosides, and second- and third-generation cephalosporins was restricted, reasons for restrictions, existence of a formal education program on new antibiotics, whether the physician respondents agreed with the practice of antibiotic restriction, what percent of requests for use of restricted agents was denied, formulary status of the drugs, the procedure for authorizing dispensing of restricted agents, and the percent of drug expenditures represented by restricted agents. Direct control (specialist authorization or restricted indications for use) was used in 62 (57%) of 108 institutions responding. Nonformulary status indirectly controlled use in 35 institutions. No significant differences in the prevalence of restrictions were found for hospital size, ownership, physician's view of the restrictions, or presence of an education program. Most (85%) of the physicians agreed with restriction practices. Cost was the reason given most frequently for restriction of the penicillins and cephalosporins, while aminoglycosides were most frequently restricted because of bacterial resistance. The specialist's oral authorization was the most common method of approval for use of restricted agents. Expenditures for restricted drugs varied widely, suggesting that different levels of control were considered "restriction" by the responding institutions. Control of antibiotic use is common in these teaching hospitals associated with medical schools. No best method for antibiotic restriction was evident.

Therapeutic substitution practices in short-term hospitals.

Hospital policies concerning the automatic interchange of therapeutically equivalent drugs were examined. A questionnaire was sent to the chief pharmacists at 6326 shot-term hospitals throughout the United States. The survey items solicited demographic data and formulary policies on generic and therapeutic substitution. A total of 2437 (39%) usable questionnaires were returned. Approximately 40% of the hospitals reported that their formulary system allows the stocking of a single product to represent a given therapeutic category. A total of 751 hospitals reported that their formulary system allows automatic dispensing of the therapeutically equivalent drug product without contacting the physician for permission. Therapeutic substitution was found particularly prevalent in federally owned hospitals. There were regional variations in the existence of therapeutic substitution. Factors that appeared to be associated with therapeutic substitution were: drug use review activity, medical school affiliation, existence of a formulary system, perceptions of favorable view by the state board of pharmacy, and favorable perception of the savings generated through bid purchasing. Reasons for not engaging in therapeutic substitution included the following: (1) would not be accepted by the physicians, (2) interferes with physicians' right to select the drug, (3) unnecessary risk of civil liability, (4) violation of laws, and (5) expected benefits do not justify the cost. Most respondents thought that physicians are usually aware of therapeutic substitutions that occur. Although they were a minority, a large percent of the respondents had a formulary system that allowed automatic interchange of generically inequivalent products within a therapeutic class of drugs. The influence of therapeutic substitution on drug therapy outcomes and cost savings need to be evaluated.

State regulatory positions concerning therapeutic substitutions in hospitals.

State regulatory agencies were surveyed to determine their views concerning hospital policies that allow therapeutic substitution. A questionnaire consisting of 10 close-ended questions was sent to the executive secretary of each board of pharmacy in the 50 states and District of Columbia. Agencies were contacted by telephone in four weeks if they did not respond. Of the 51 jurisdictions surveyed, 34 answered all of the questions, 13 answered some, and 4 did not respond. None of the 13 partial respondents expressed their views concerning the legality of therapeutic substitution in the institutional setting. Fifteen agencies indicated they would view this practice as illegal, 17 said it is in accordance with policies established by the P & T committee and therefore not subject to state or federal regulation, and two agencies gave qualified responses. Seven agencies indicated enforcement procedures would be initiated if they were to learn that therapeutic substitution was being practiced in a hospital within their jurisdiction. Three states were uncertain about what action would likely be taken, 23 indicated no action would be taken, and two gave qualified responses. All 39 agencies responding to the question indicated they had never taken action against the practice of a formulary system that allows therapeutic substitution. Few state laws address the practice of therapeutic substitution, and opinions of regulatory agencies vary. Moreover, the opinions rendered have not been tested in the courts.

Therapeutic substitution and the hospital formulary system.

Physicians consent and statutory regulations relating to therapeutic substitution are discussed. Some hospitals have adopted policies allowing the interchange of a chemically inequivalent product deemed therapeutically identical by the P & T committee. In the absence of statutory regulation, hospital pharmacists usually refer to (1) the physician's agreement to abide by hospital bylaws (including the formulary system) when joining the hospital staff, or (2) prescription blanks and order sheets preprinted with the statement "substitution permitted unless otherwise indicated" as the legal authority for therapeutic substitution. Only two states have addressed the legality of therapeutic substitution. An opinion of the Oregon Attorney General and a Washington state statute both authorize therapeutic substitution under certain circumstances if the prescriber has given prior consent. Neither of the states specifies, however, whether the agreement of prescribers to abide by hospital bylaws constitutes authorization of therapeutic substitution. It is proposed that state boards of pharmacy and state legislatures draft laws that address therapeutic substitution and specify acceptable methods of consent.

Computer-assisted antibiotic use review.

The use of a computer system for an antibiotic review program is described. A commercial system was selected as the software base for the development of the antibiotic use review (AUR) program. The AUR system is composed of three parts: (1) editing and verifying data from the patient's pharmacy profile card, (2) updating the data base, and (3) generation of reports. The system is flexible in its reporting capabilities. Potential functions of the system include identifying patterns of bacterial resistance. The computer system is an efficient tool for the clinical review of antibiotic use in a quality assurance program.

Evaluation of albumin use by medical audit.

The appropriateness of albumin prescribing and accuracy of records of albumin use were studied at a 476-bed hospital. Medical records of 15 adults who had undergone surgery within one week of albumin administration were compared with eight prescribing and charting criteria that were developed by pharmacists. Charts of patients who did not meet every criteria were reviewed by a committee to determine if exceptions to the criteria were justifiable. Albumin prescribing was empirical for approximately 60% of the patients. Albumin use as judged by laboratory values was inappropriate in three patients. Charting of the amount and rate of albumin administered was inaccurate, incomplete or difficult to interpret for eight (53%) of the patients. The dosage of albumin prescribed was inappropriate for two (13%) patients. Appropriate concomitant therapy (e.g., packed red blood cells) was not prescribed for two patients. For only three patients did the patient's charge correspond to the amount charted as being administered. On an annual basis, patient charges for albumin were projected to be $9,321 less than the hospital's cost for the product. The audit identified problems in albumin prescribing and charting that, when corrected, would result in cost savings and improved patient care.