Peter J. Jewesson

Industry Sponsorship and Authorship of Clinical Trials Over 20 Years

BACKGROUND The pharmaceutical industry has become a major source of funding for biomedical research. Our general observation is that pharmaceutical industry employees are appearing with increasing frequency as coauthors of clinical trial publications. OBJECTIVE To characterize clinical trial funding, reporting, and sources; investigate author—industry affiliation; and describe clinical outcome trends over time. METHODS We reviewed 500 randomly selected clinical trials published in 5 influential medical journals over a 20-year period (1981–2000). RESULTS Of the 500 clinical trials reviewed, 181 (36%) involved pharmaceutical industry as an independent (n = 104) or joint (n = 77) sponsor and 180 (36%) involved a peer-review funding source; the balance (139; 28%) lacked any declared sponsorship. The percentage of industry-sponsored clinical trials increased to 62% during 1997–2000. The percentage of nonprofit sponsored clinical trials remained constant over time, while the percentage of those without funding declaration declined. Reported author affiliation with industry increased to 66% of clinical trials sponsored only by industry. An increase in the percentage of clinical trials with reported author—industry affiliation was observed for all journals. Regardless of funding source, the majority of clinical trials reported clinical outcomes that favored the study drug. CONCLUSIONS Pharmaceutical industry—sponsored and mixed-funding clinical trials are common, and the relative incidence of published trials with these declared funding sources in the 5 journals reviewed has increased. Industry employees are appearing as coauthors of clinical trial publications with increasing frequency.

Double-blind comparison of teicoplanin versus vancomycin in febrile neutropenic patients receiving concomitant tobramycin and piperacillin: effect on cyclosporin A-associated nephrotoxicity.

A prospective, randomized, and double-blind study comparing teicoplanin with vancomycin in the initial management of febrile neutropenic patients was conducted. Teicoplanin was administered at 6 mg per kg of body weight every 24 h (q24h) intravenously (i.v.) after initial loading at 6 mg/kg q12h for three doses. Vancomycin was administered at 15 mg/kg q12h i.v. Patients also received piperacillin (3 g q4h i.v.) and tobramycin (1.5 to 2.0 mg/kg q8h i.v.). Of 53 patients enrolled, 50 were judged to be evaluable. Among these, 25 received teicoplanin and 25 received vancomycin. At enrollment, both groups were comparable in age, sex, renal function, underlying hematologic condition, and concurrent therapy. Both groups had similar sites of infection and microbial pathogens. Empirical antimicrobial therapy resulted in the cure of or improvement in 23 (92%) teicoplanin patients and 21 (84%) vancomycin patients (P = 0.67). Failures occurred with two vancomycin patients but no teicoplanin patients. Clinical response was indeterminate for two patients in each group. Adverse reactions occurred significantly more often in the vancomycin group than in the teicoplanin group (P = 0.01), and these reactions required the termination of the study regimens of 6 vancomycin versus 0 teicoplanin patients (P = 0.02). Nephrotoxicity was observed more frequently in the vancomycin group (10 versus 2 patients; P = 0.02). Subgroup analysis revealed a significant deterioration of renal function when vancomycin and cyclosporin A, but not teicoplanin and cyclosporin A, were used concurrently (P = 0.02). Among patients who received vancomycin and amphotericin B or teicoplanin and amphotericin B concurrently, deterioration in renal function was equivalent in both groups. Teicoplanin in the dosage employed was tolerated better than vancomycin in the empirical treatment of fever and neutropenia in our patient population.

Adverse reactions in a dose-ranging study with a new long-acting fluoroquinolone, fleroxacin.

New fluoroquinolones have generally been well tolerated. In a double-blind evaluation of oral fleroxacin, using 400, 600, or 800 mg once daily for 7 days in an ambulatory setting for treatment of uncomplicated genital infections, we encountered unexpectedly high rates of adverse reactions. The objective of this analysis was to determine whether any factors in addition to dose could be found to account for our observations. Adverse reactions developed in 66 (84%) of 79 individuals, and severe reactions arose in 38 (48%). Most frequent were central nervous system reactions (70%), with insomnia being especially frequent (49%); gastrointestinal reactions (39%) and photosensitivity reactions (10%) were also common. Development of any reaction (central nervous system reactions, insomnia, and severe intestinal reactions) was dose related. Development of photosensitivity reactions correlated with an outdoor occupation. No other factors, including usual daily caffeine use, correlated with the development of adverse reactions. In our study, fleroxacin taken as a single daily 600- or 800-mg dose was associated with an unacceptably high rate of adverse reactions. Other studies are required to determine whether this problem is unique to fleroxacin or will occur with higher doses of other fluoroquinolones possessing similar chemical modifications and/or good tissue penetration and very long half-lives.

Cost Analysis of an Adult Outpatient Parenteral Antibiotic Therapy (OPAT) Programme A Canadian Teaching Hospital and Ministry of Health Perspective

AbstractBackground: Outpatient parenteral antibiotic therapy (OPAT) programmes have become prevalent over the past 2 decades. From the US perspective, these programmes have been shown to reduce healthcare costs. No comprehensive analysis has been published from the Canadian perspective. Objective: To describe a Canadian OPAT programme for the 3-year period since its inception and to conduct a treatment cost analysis. Design and methods: Demographics and resource utilisation data (health professional labour, laboratory and diagnostic tests, antimicrobials, delivery, home nursing care, catheters and catheter placement) were prospectively collected for enrollees in the OPAT programme over the evaluation period. Avoided hospital resource utilisation was estimated via retrospective chart review by the investigators. Costs were retrospectively assigned to each resource and total cost avoidance by the OPAT programme was determined from each perspective. Perspective: A teaching hospital and a provincial Ministry of Health (MOH). Main outcome measures and results: 140 treatment courses were initiated for 117 adult patients (mean age 54 years) who were enrolled into the programme. Mean pre-OPAT length of hospital stay was 12 days, and mean OPAT duration was 22.5 days. Bone/joint (39%), skin and soft tissue (16%), cardiac (13%) and respiratory tract (12%) infections were the most common infections managed. The most commonly used antimicrobials were vancomycin (29%), cloxacillin ± gentamicin (22%) and ceftriaxone ± gentamicin (11%). 85%of enrollees successfully completed their planned antimicrobial treatment regimens. Premature discontinuation of antimicrobial therapy for various reasons occurred in the remaining 15% of courses. The mean cost per treatment course of OPAT was 1910 Canadian dollars (

Intravenous-to-Oral Stepdown Program: Four Years of Experience in a Large Teaching Hospital

Can) from the hospital perspective and

An assessment of quality of sleep and the use of drugs with sedating properties in hospitalized adult patients

Can6326 from the MOH perspective. Assuming that patients would have otherwise completed their antimicrobial therapy in hospital, the mean cost per treatment course was estimated to be

Quality-of-Life Assessment in an Outpatient Parenteral Antibiotic Program

Can14 271. The overall cost avoidance of the OPAT programme was

Sequential Antibiotic Therapy: Effective Cost Management and Patient Care

Can1 730 520 (hospital perspective) and

Cost-Effectiveness and Value of an IV Switch

Can1 009 450 (MOH perspective) over the 3-year assessment period. Sensitivity analyses revealed the results to be robust to plausible changes. Conclusions: This analysis supports the premise that an adult OPAT programme can substantially reduce healthcare costs in the Canadian healthcare setting.

Selecting antibacterials for outpatient parenteral antimicrobial therapy: Pharmacokinetic-pharmacodynamic considerations

OBJECTIVE: To assess the impact of an intravenous-to-oral (iv-po) stepdown program on the relative use of oral and parenteral dosage forms of select antimicrobials. DESIGN: A retrospective review of drug utilization records before and after a trial comparing metronidazole and clindamycin prescribing trends from a 12-month baseline period to a four-year follow-up period. SETTING: One thousand-bed Canadian tertiary care referral teaching center. INTERVENTION: An authorized iv-po stepdown program was developed to promote the oral route of drug administration. Reminders of iv-po stepdown were produced for metronidazole and clindamycin and these notes were sent to nursing units with the parenteral dosage form. The notes then were attached to the front of the health record to serve as a reminder to prescribers that an equally effective, well-tolerated, and less-expensive oral dosage form was available for use. RESULTS: A 44 percent relative increase in the use of oral metronidazole and a 79 percent relative increase in the use of oral clindamycin occurred. When acquisition and delivery costs were considered, cumulative cost savings from 1988 to 1991 resulted for metronidazole (