DOCSLIB.ORG

Identifying Optimal Femoral Neck Fractures Treatments Using a Network Meta-Analysis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Identifying Optimal Femoral Neck Fractures Treatments Using a Network Meta-Analysis Identifying optimal femoral neck fractures treatments using a network meta-analysis Jacob Lavigne Experimental Surgery McGill University September 2018 A thesis submitted to McGill University in partial fulfillment of the requirements of the degree of Doctor of Philosophy in Experimental Surgery © Jacob Lavigne, 2018 Jacob Lavigne Identifying optimal femoral neck fractures treatments using a network meta-analysis PhD Thesis Table of Contents Abstract ......................................................................................................................................... 3 French ........................................................................................................................................ 3 English ....................................................................................................................................... 4 Acknowledgements ....................................................................................................................... 5 Contribution of authors ................................................................................................................ 6 Introduction .................................................................................................................................. 7 Background (literature review) ................................................................................................. 7 Patient profile ........................................................................................................................ 7 Rates and socioeconomic burden ......................................................................................... 8 Anatomy of the hip ................................................................................................................ 9 Etiology and fracture patterns ............................................................................................ 13 Diagnosis and Treatment ..................................................................................................... 19 Burden of illness .................................................................................................................. 36 Rationale ................................................................................................................................. 43 Research Questions ................................................................................................................. 44 Objectives ................................................................................................................................ 48 Hypotheses .............................................................................................................................. 48 Methodology ............................................................................................................................... 50 Review protocol registration ................................................................................................... 50 Database search ...................................................................................................................... 51 Selection criteria ..................................................................................................................... 53 Bias Assessment ...................................................................................................................... 55 Data extraction and cleaning .................................................................................................. 56 Network Meta-Analysis ........................................................................................................... 58 Direct treatment effect calculations ................................................................................... 58 Software and model selection ............................................................................................. 59 Indirect and mixed treatment effect calculations ............................................................... 60 Assumption testing .............................................................................................................. 60 Sensitivity analyses .............................................................................................................. 61 EQ-5D/Mortality Partial Order Set Analysis ............................................................................ 62 1 Jacob Lavigne Identifying optimal femoral neck fractures treatments using a network meta-analysis PhD Thesis Results ......................................................................................................................................... 62 Prisma Flow Chart (combined) ................................................................................................ 63 EQ-5D results ........................................................................................................................... 65 Sample characteristics ......................................................................................................... 65 Bias Assessment .................................................................................................................. 69 NMA, Assumption Tests and Ranking ................................................................................. 70 Mortality .................................................................................................................................. 75 Sample Characteristics ........................................................................................................ 76 Bias Assessment .................................................................................................................. 80 NMA, Assumption Testing and Ranking .............................................................................. 82 AVN .......................................................................................................................................... 87 Sample characteristics ......................................................................................................... 87 Bias Assessment .................................................................................................................. 90 NMA, Assumption Testing and Ranking .............................................................................. 91 EQ-5D/Mortality Partial Order Set Analysis ............................................................................ 96 Discussion.................................................................................................................................... 99 Interpretations and original contributions ............................................................................. 99 Critique of the literature ....................................................................................................... 112 Limitations and solutions (next steps) .................................................................................. 117 Conclusion and summary .......................................................................................................... 122 Appendix A ................................................................................................................................ 123 Appendix B ................................................................................................................................ 135 Appendix C ................................................................................................................................ 135 Appendix D ................................................................................................................................ 140 Bibliography .............................................................................................................................. 141 2 Jacob Lavigne Identifying optimal femoral neck fractures treatments using a network meta-analysis PhD Thesis Abstract French Les fractures du col du fémur sont des blessures graves caractérisées par un fardeau de maladies important et un taux de mortalité élevé. Le taux de ces blessures est estimé à augmenter et créer un poids considérable pour le secteur de la santé dans les prochaines années. En raison de l'impact de cette blessure sur ceux qui en souffrent ainsi que sur la société, il est nécessaire d'identifier le traitement optimisant la guérison. Pour ce faire, une méta-analyse de réseau a été réalisée selon trois résultats (qualité de vie, mortalité et ostéonécrose avasculaire de la tête du fémur) et les traitements ont été classés en fonction de chaque résultat. De plus, les résultats de l'analyse de la qualité de vie et de la mortalité ont été combinés pour donner un classement sommatif. L’arthroplastie totale de la hanche sans ciment a été classée comme étant le meilleur traitement pour la qualité de vie, tandis que l'hémiarthroplastie unipolaire cimentée était le meilleur en termes de mortalité. Aucun contraste significatif n'a toutefois été trouvé pour cette dernière. La capsulotomie avec réduction ouverte et une greffe osseuse iliaque a été classé la meilleure pour l’ostéonécrose. Les broches étaient significativement supérieures aux vis canulées pour cette complication. Le classement combiné suggère que l’arthroplastie totale avec ou sans ciment ou l’hémiarthroplastie avec ciment devraient être utilisés comme traitement des fractures du col du fémur déplacées chez les personnes
Load more

Recommended publications
  • Nitrate Prodrugs Able to Release Nitric Oxide in a Controlled and Selective
    Europäisches Patentamt *EP001336602A1* (19) European Patent Office Office européen des brevets (11) EP 1 336 602 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.7: C07C 205/00, A61K 31/00 20.08.2003 Bulletin 2003/34 (21) Application number: 02425075.5 (22) Date of filing: 13.02.2002 (84) Designated Contracting States: (71) Applicant: Scaramuzzino, Giovanni AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU 20052 Monza (Milano) (IT) MC NL PT SE TR Designated Extension States: (72) Inventor: Scaramuzzino, Giovanni AL LT LV MK RO SI 20052 Monza (Milano) (IT) (54) Nitrate prodrugs able to release nitric oxide in a controlled and selective way and their use for prevention and treatment of inflammatory, ischemic and proliferative diseases (57) New pharmaceutical compounds of general effects and for this reason they are useful for the prep- formula (I): F-(X)q where q is an integer from 1 to 5, pref- aration of medicines for prevention and treatment of in- erably 1; -F is chosen among drugs described in the text, flammatory, ischemic, degenerative and proliferative -X is chosen among 4 groups -M, -T, -V and -Y as de- diseases of musculoskeletal, tegumental, respiratory, scribed in the text. gastrointestinal, genito-urinary and central nervous sys- The compounds of general formula (I) are nitrate tems. prodrugs which can release nitric oxide in vivo in a con- trolled and selective way and without hypotensive side EP 1 336 602 A1 Printed by Jouve, 75001 PARIS (FR) EP 1 336 602 A1 Description [0001] The present invention relates to new nitrate prodrugs which can release nitric oxide in vivo in a controlled and selective way and without the side effects typical of nitrate vasodilators drugs.
    [Show full text]
  • June 2011 Circular No
    7 th June 2011 Circular No. P06/2011 Dear Healthcare Professional, Re: European Medicines Agency finalises review of bisphosphonates and atypical stress fractures Bisphosphonates have been authorised in the EU for hypercalcaemia and the prevention of bone problems in patients with cancer since the early 1990s. They have also been available since the mid 1990s for the treatment of osteoporosis and Paget’s disease of the bone. Bisphosphonates include alendronic acid, clodronic acid, etidronic acid, ibandronic acid, neridronic acid, pamidronic acid, risedronic acid, tiludronic acid and zoledronic acid. They are available in the EU as tablets and as solutions for infusion under various trade names and as generic medicines2. In 2008, the CHMP’s Pharmacovigilance Working Party (PhVWP) noted that alendronic acid was associated with an increased risk of atypical fracture of the femur (thigh bone) that developed with low or no trauma. As a result, a warning was added to the product information of alendronic acid-containing medicines across Europe. The PhVWP also concluded at the time that it was not possible to rule out the possibility that the effect could be a class effect (an effect common to all bisphosphonates), and decided to keep the issue under close review. In April 2010, the PhVWP noted that further data from both the published literature and post- marketing reports were now available that suggested that atypical stress fractures of the femur may be a class effect. The working party concluded that there was a need to conduct a further review to determine if any regulatory action was necessary. Page 1 of 3 Medicines Authority 203 Level 3, Rue D'Argens, Gzira, GZR 1368 – Malta.
    [Show full text]
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
    US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG .
    [Show full text]
  • Effects of Teriparatide and Bisphosphonate on Spinal Fusion Procedure
    Effects of Teriparatide and Bisphosphonate on Spinal Fusion Procedure: A systematic review and network meta-analysis (Supplementary) Index of Supplementary Supplementary File 1. Database and search strategy Supplementary File 2. Risk of bias Supplementary File 3. Forest plot of fusion rate Supplementary File 4. Cumulative probability and SUCRA of fusion rate Supplementary File 5. Inconsistency test for network meta-analysis of fusion rate Supplementary File 6. Publication bias in network meta-analysis of fusion rate Supplementary File 7. Forest plot of ODI Supplementary File 8. Cumulative probability and SUCRA of ODI Supplementary File 9. Inconsistency test for network meta-analysis of ODI Supplementary File 10. Publication bias in network meta-analysis of ODI Supplementary File 11. Forest plot of adverse event Supplementary File 12. Cumulative probability and SUCRA of adverse event Supplementary File 13. Inconsistency test for network meta-analysis of adverse event Supplementary File 14. Publication bias in network meta-analysis of adverse event Supplementary 1 Database and search strategy Supplementary 1 Database and search strategy Database Search strategy #1. terrosu #2. forteo #3. teriparatide #4. parathyroid hormone #5. PTh #6. #1 OR #2 OR #3 OR #4 OR #5 #7. bonviva #8. alendronate #9. fosamax #10. olpadronate #11. neridronate #12. nericia #13. pamidronate #14. aredia #15. APD #16. zometa #17. avlasta #18. risedronate Primary #19. actonel search #20. boneva strategy #21. bisphosphonate #22. ibandronic #23. disambiguation #24. zoledronate #25. #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 #26.
    [Show full text]
  • Tissue Engineering Approaches to the Treatment of Bisphosphonate-Related Osteonecrosis of the Jaw George Bullock
    Tissue engineering approaches to the treatment of bisphosphonate-related osteonecrosis of the jaw George Bullock A thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy The University of Sheffield Faculty of Engineering Department of Materials Science and Engineering March 2019 Abstract Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a disease defined by necrotic jaw bone that has become exposed through the surrounding soft tissue, which affects patients with osteoporosis and bone metastases taking the anti-resorptive bisphosphonate (BP) drugs. Currently this disease is without a specific treatment, in part due to its complex, and not fully understood, pathophysiology. This research used tissue engineering principles to further investigate the effects of BPs on the soft tissue, both in two and three dimensions, and investigated a potential preventative treatment for the disease in vitro. The BPs investigated were pamidronic acid (PA) and zoledronic acid (ZA), two BPs most commonly associated with BRONJ. We explored the effects of PA and ZA on human oral fibroblasts and keratinocytes at clinically relevant concentrations in 2D. Both PA and ZA caused significant reductions to metabolic activity, and further study indicated an increase in apoptosis in fibroblasts, and apoptosis and necrosis in keratinocytes. PA and ZA led to a significant reduction in proliferation, and ZA reduced the adhesion of keratinocytes. However, BPs did not affect cellular migration. A 3D oral mucosa model was used to investigate PA and ZA. PA prevented the stratification of newly formed epithelia and reduced the thickness of healthy epithelia. ZA showed the same effects, but at higher concentrations was also toxic.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • WHO-EMP-RHT-TSN-2018.1-Eng.Pdf
    WHO/EMP/RHT/TSN/2018.1 The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization [2018] Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO.
    [Show full text]
  • Bisphosphonates and Osteonecrosis of the Jaw: Update on Risk Minimisation Including New Recommendations on Preventative Dental Measures
    IRIS H MEDICINE S BOA RD BISPHOSPHONATES AND OSTEONECROSIS OF THE JAW: UPDATE ON RISK MINIMISATION INCLUDING NEW RECOMMENDATIONS ON PREVENTATIVE DENTAL MEASURES Bisphosphonates are a class of medicines together with current guidelines produced by approved for various indications related to their learned societies. The review also incorporated inhibitory effect on bone resorption in certain advice from a group of experts representing all malignant and benign diseases, including areas of medicine where bisphosphonates are prophylaxis and treatment of osteoporosis; used, dentistry and bone surgery, and treatment of Paget’s disease; and as part of some representatives of patients’ organisations.Whilst it cancer regimens, particularly for metastatic bone is recognised that risk factors for ONJ are multiple cancer and multiple myeloma. Detailed information and currently not fully elucidated, the most on the approved indications for use, warnings and significant risk factors for the development of ONJ precautions etc. is described in the product in association with bisphosphonates are information for the individual products concerned considered to be bisphosphonate potency, route of (alendronic acid, clodronic acid, etidronic acid, administration and cumulative dose of ibandronic acid, neridronic acid, pamidronic acid, bisphosphonate exposure. A history of dental risedronic acid, tiludronic acid, zoledronic acid). disease, including invasive dental procedures, The risk of osteonecrosis of the jaw (ONJ) in dental trauma, periodontal disease, and poorly association with the use of bisphosphonates has fitting dentures is associated with an increased risk been closely monitored and reviewed at EU level of ONJ. Further research is needed to increase on several occasions, with a number of risk knowledge about the underlying mechanisms and minimisation measures taken, including updates risk factors for ONJ, and about how best to minimise to the product information and communication to these risks.
    [Show full text]
  • Assessment Report for Bisphosphonates Containing Medicinal Products
    13 July 2011 EMA/725125/2011 Patient Health Protection Assessment report for bisphosphonates containing medicinal products International non-proprietary names: Alendronic acid, clodronic acid, etidronic acid, ibandronic acid, neridronic acid, pamidronic acid, risedronic acid and tiludronic acid Procedure No.: EMEA/H/A-31/1279 Assessment Report as adopted by the CHMP with all information of a commercially confidential nature deleted. 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7523 7051 E-mail [email protected] Website www.ema.europa.eu An agency of the European Union © European Medicines Agency, 2011. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 3 1.1. Referral of the matter to the CHMP ....................................................................... 3 2. Scientific discussion ................................................................................ 3 2.1. Introduction ...................................................................................................... 3 2.2. Non-clinical aspects ............................................................................................ 4 2.3. Clinical aspects .................................................................................................. 4 2.3.1. Introduction ..................................................................................................
    [Show full text]
  • Page 1 of 51 NO. 1901/2006 Wissenschaftliche Prüfungsarbeit
    ARTICLE 45 EU WORKSHARING PROCEDURE CONDUCTED ACCORDING TO PAEDIATRIC REGULATION (EC) NO. 1901/2006: WHAT HAS BEEN ACCOMPLISHED FOR PAEDIATRIC USE ? - A RETROSPECTIVE ANALYSIS Wissenschaftliche Prüfungsarbeit zur Erlangung des Titels „Master of Drug Regulatory Affairs“ der Mathematisch-Naturwissenschaftlichen Fakultät der Rheinischen Friedrich-Wilhelms-Universität Bonn vorgelegt von Dr. Elke Maneke aus Celle Bonn 2015 Page 1 of 51 Betreuer und 1. Referent: Professor Dr. Birka Lehmann Zweiter Referent: Dr. Ingrid Klingmann Page 2 of 51 Summary The lack of information and availability of appropriate pharmaceutical formulations exposed children to an increased risk to experience adverse drug reactions due to inappropriate dosing information including a risk for insufficient or even missing efficacy. Consequently, a variety of measures have been implemented by Regulation (EC) No.1901/2006 as amended in order to ameliorate medicinal care of paediatric populations. With introduction of Article 45 (1) of the Paediatric Regulation, paediatric use information in the SmPC was supposed to be improved by assessing study data from paediatric clinical trials, which have been completed before 26 January 2007. Considering the line-listings submitted by MAHs in January 2008, 167 studies have been provided for centrally authorized medicines; 18,000 studies for nationally authorized small molecules; 609 studies for nationally authorized vaccines and 625 studies for herbal and homoeopathic medicines. Since the majority of paediatric studies falling under the scope of an Article 45(1) of Regulation (EC) No.1901/2006 have been submitted for nationally licensed medicinal products, the retrospective analysis focussed exclusively on active substances subject to an Article 45 EU Worksharing Procedure. Assessment reports of 162 active substances encompassing small molecules; vaccines and biologics have been reviewed and summarized in Annex A.
    [Show full text]
  • International Comparison of Medicines Usage: Quantitative Analysis
    International Comparison of Medicines Usage: Quantitative Analysis Phill O’Neill, Jon Sussex Contents List of abbreviations 2 Executive summary 3 1. Introduction and background 4 2. Method2. 5 2.1 Selection of comparator countries and therapy areas 5 2.2 Data used in the study 6 2.3 Analysis and presentation 9 2.4 Limitations in the presentation of the analysis 10 3. Results 3. 11 3.1 Overview 11 3.2 Results by therapy area 13 Cancer14 Statins16 Acute myocardial infarction 16 Alteplase for stroke 17 Novel oral anti-coagulants 17 2nd generation anti-psychotics 18 Dementia 18 Multiple sclerosis 19 Osteoporosis 19 TNF medicines 20 Hepatitis C 20 Respiratory distress syndrome 21 Respiratory syncytial virus 22 Wet age-related macular degeneration 22 3.3 Summary of the results by therapy area 23 References 27 Appendix 1: Benchmarking usage of HIV and diabetes medicines 2012/13 28 Appendix 2: List of medicines included in the analysis 30 1 List of abbreviations ABPI Association of the British Pharmaceutical Industry Acute MI Acute myocardial infarction ATC Anatomic therapeutic chemical coding DDD Defined daily dose DH Department of Health DPP-4 inhibitors Dipeptidyl peptidase-4 inhibitor medicines DTP Direct to pharmacy distribution model EphMRA European Pharmaceutical Market Research Association EU5 France, Germany, Italy, Spain, UK GLP-1 agonists Glucagon-like peptide-1 agonist medicines HIV Human immunodeficiency virus IMS Intercontinental Medical Statistics NICE National Institute for Health and Care Excellence NOAC Novel oral anti-coagulant
    [Show full text]
  • EMEA: CHMP Assessment Report on Bisphosphonates and Osteonecrosis of The
    European Medicines Agency London, 24 September 2009 EMEA/CHMP/291125/2009 CHMP ASSESSMENT REPORT ON BISPHOSPHONATES AND OSTEONECROSIS OF THE JAW Procedure under Article 5(3) of Regulation (EC) No 726/2004 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK Tel. (44-20) 74 18 84 00 Fax (44-20) 74 18 86 68 E-mail: [email protected] http://www.emea.europa.eu © European Medicines Agency, 2009. Reproduction is authorised provided the source is acknowledged. 1 BACKGROUND INFORMATION ON THE PROCEDURE On 19 February 2009, Denmark (DK) presented to the EMEA a request for a CHMP opinion under Article 5(3) of Regulation (EC) No 726/2004 to review issues related to the adverse event osteonecrosis of the jaw (ONJ) following the use of bisphosphonates. Currently, medicinal products authorised in the European Union containing bisphosphonates are manufactured using alendronic acid, clodronic acid, etidronic acid, ibandronic acid, neridronic acid, pamidronic acid, risedronic acid, tiludronic acid, and zoledronic acid as active substance. Centrally authorised bisphosphonate-containing medicinal products include Aclasta and Zometa (zoledronic acid), Bondenza, Bonviva, Bondronat (ibandronic acid) and Adrovance and Fosavance (alendronic acid). A first informal class review performed by the Pharmacovigilance Working Party (PhVWP) in 2005 resulted in revised labelling aiming at minimising the risk for developing ONJ. During 2007 increasing concern emerged that these risk minimisation measures did not suffice, as the numbers of spontaneously reported cases did not decline substantially. A second class review was therefore initiated in December 2007. Information was requested from the Marketing Authorisation Holders (MAHs) of bisphosphonate-containing medicinal products with Lists of Questions issued in December 2007 and April 2008.
    [Show full text]