1 / 31

"Clinical Trials and Clinical Endpoints"

"Clinical Trials and Clinical Endpoints" . James R. Bradford, DVM, Dipl. ABVP Pharmacia Animal Health. Mycoplasmal Pneumonia. Clinical and production disease Recognized financial impact early ’70’s Research with Lincomycin began in 1974

guinevere
Download Presentation

"Clinical Trials and Clinical Endpoints"

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. "Clinical Trials and Clinical Endpoints" James R. Bradford, DVM, Dipl. ABVP Pharmacia Animal Health

  2. Mycoplasmal Pneumonia • Clinical and production disease • Recognized financial impact early ’70’s • Research with Lincomycin began in 1974 • FDA approval “for the reduction in severity of pneumonia due to Mycoplasma hyopneumoniae” granted in 1978

  3. Mycoplasmal Pneumonia of Swine Is… • A distinct clinical disease with distinct lesions and a recognized cause • Often part of a more severe respiratory disease complex • Potentiator for Pasteurella multocida, some APP, PRRSV (Pijoan, Thacker) • Additive with Swine Influenza Virus (Thacker and Halbur) • Treatable as a single entity or as part of a complex

  4. Clinical Endpoints • % of pigs affected • Number of lobes involved in each pig • % of lung involved • Respiratory score • Cough • Respiratory difficulty

  5. Pivotal Studies • In vitro MIC determination for challenge strain correlated with concentration at site of infection • Challenge trials - dose titration, duration of treatment • Field efficacy trials – dose confirmation, fixed duration

  6. Challenge Model • Must have pigs free of M. hyopneumoniae • Usually very mild disease compared to field challenge • All animals at same stage of infection • Can treat at earliest appearance of clinical signs • May give false sense of efficacy

  7. Treatments – Challenged Pigs

  8. Treatment Initiation • At onset of clinical signs (Clinical disease present) • Expected to be day 10 PI • Actually day 8 PI – 13.6% of pigs coughing

  9. Clinical Endpoints • % of lobes with lesions – incidence measure • % of total lung with lesions – severity measure

  10. Lesions Observed a a b b a a b b a,b different, p<.05

  11. Duration of Treatment% Lung with Lesions

  12. Conclusion • In the challenge model, lincomycin at 220 and 330 ppm resulted in a significant reduction in severity and incidence of lesions caused by M. hyopneumoniae. • The optimum treatment regime based on lesion and performance data was 220 ppm for 21 days.

  13. Field Trials • Herds with history of problems with MPS • Pigs at an age already likely infected with MPS

  14. 4 Field Trials • Indiana, Florida, Alabama, and Minnesota • Pigs 8-12 weeks of age • 6 cohort pigs killed and necropsied to confirm disease • 3 sites tested 4 inclusion rates: 0,110, 220, 330 ppm • 1 site tested 0, 220 ppm only

  15. Clinical Observations • Gross Pathology • Number of lobes involved • Estimated percent of total lung involved • Microscopic Pathology • Right cardiac lobe sampled based on lesion location for histopathologic scoring • Production Parameters (ADG and ADFI)

  16. Replications per Treatment

  17. % Pigs with MPS Lesions An estimate of the number of pigs exposed for sufficient time to develop lesions

  18. % Lobes Affected –All Pigs a ab b b % a,b different, p<.05 Lincomycin suppressed the advancement of the disease process.

  19. Mean % Total Lung Involved All Pigs a ab % b b a,b different, p<.10 220 ppm reduced severity by 49%, 110 ppm by 27%(ns)

  20. Lesions Scored Microscopically for Aging of MP Lesion % of Pigs a,b,cMeans in the same column with different superscripts differ significantly (p<.05)

  21. Trial Conclusion • Lincomycin administered in the feed at 220 ppm for 21 days is effective in the reduction of pneumonia lesions associated with Mycoplasma hyopneumoniae.

  22. Conclusions Based on 25 Years Experience • It is possible to measure clinical endpoints of mycoplasmal pneumonia both in clinical trials and in field trials. • The approval process to provide substantial proof of efficacy was was rigorous and has stood the test of time. • Production parameters are an important auxiliary component of the research process, but not the approval process.

  23. If We Designed a Plan Today….. • Similar approach • Laboratory – in vitro determination of efficacy correlated with drug at the site of infection • Challenge – validated challenge models run in production-like facilities for dose and duration selection • Field trials – field efficacy trials with dose and duration confirmation

  24. If We Designed a Plan Today….. • Field efficacy trials – • Multi-location – production units • History of respiratory disease with M.hyopneumoniae as a key component • Co-infections with PRRSv acceptable/welcome • Experimental unit ? – pen, room, barn, site

  25. If We Designed a Plan Today….. • Clinical Endpoints • % lung involved and % pigs affected would still be critical measurements • % lung involved could be measured more accurately today with grids and computer calculation and could be measured on a sample of pigs killed over the course of the trial • Fluorescent antibody test would provide better confirmation of cause of pneumonia

  26. Lincomix effects on culling Pharmacia - Bradford 9/00

  27. Lincomix pulled

  28. Lincomix pulled

  29. Lincomix pulled

More Related