Off-label Prescribing

David Cavalla, is an expert on secondary uses for existing drugs, or drug repurposing. He currrently operates through his consultancy, Numedicus Ltd, having worked in drug repurposing for 15 years. Previously he was CEO of Arachnova, and prior to that held various senior positions in pharmaceutical drug discovery at GSK and Napp Research Centre. He has written widely on drug discovery strategy, and is the author of 70 published papers and patents.

• Foreword, ixAcknowledgement, xiAuthor’s note on the cover design, xiiiIntroduction, xv1 What is off-label medication, and how prevalent is it?, 1What is ‘off-label’ medicine?, 2Scope of the issue, 82 Where it all went right: new uses for existing drugs supported by good evidence, 19Examples where products have been through regulatory approval for a secondary use, 19Finasteride: pseudohermaphroditism and hair growth, 19Sildenafil: re-tasking the blue pill for a life-threatening illness, 21Doxycycline: from killing bugs to protecting gums, 22Raloxifene: from cancer to bone disease and back again, 23Galantamine: using snowdrops to improve memory, 24Cyclosporine: preventing immune attack on organs and skin, 25Dimethyl fumarate: a remarkable drug for multiple sclerosis, 26Botox: a drug to kill or cure you, 27Examples where evidence is uncertain and not to regulatory standards, 28Tricyclic antidepressants: for curing more than emotional pain, 28Aspirin for cancer, 30Retrospective data: looking back to create future therapies, 303 Shared decision making and consent, 33Viewpoint of the patient, 34Viewpoint of the prescriber, 37Professional guidelines, 38Patient awareness, 41Practitioner attitudes, 41Diagnosis, 444 Gaming the system: the role of the pharmaceutical industry, 47Normal drug development and drug repurposing development, 48Gaming the system, 53Orphan use, 56Pharmaceutical marketing, 61Expanding uses for non-pharmaceuticals, 64DTC advertising, 64Patents and genericisation, 65Conclusion, 685 Do no harm: Safety and efficacy, 71Relative safety, 73Different therapeutic uses, 73Chronic versus acute dosing, 78Different dose, 81Differences between children and adults, 82Other patient populations, 86Fatal ADRs, 87Quality of evidence, 88Strong evidence, 89Poor evidence, 91Doctors do not know evidence, 94Proximity of off-label to on-label, 96Debunking medical myths, 1016 Liability, injustice and reimbursement: who should pay?, 105A prescriber’s ethical and professional duties, 105Medical professional participation in off-label promotion, 105A prescriber’s legal position, 106Consent, 106Liability, 111Reimbursement, 113Compendia, 115NICE, 117Compassionate access, 120Cost, as a driver for off-label medicine, 1217 The role of regulation in off-label medicine, 125Regulators do not regulate medical practice, 126Off-label marketing, 128Off-label fines, 130Whistle-blowers, 134European situation, 134Tip of the iceberg, 136Free speech, 1388 Justifying unapproved medicine, 143Constraints on making changes, 144Moves to enhance off-label medicine, 145Diagnosis shifting, 146A partial solution: clinical trial transparency, 147A solution based on increased regulatory supervision, 152My solutions, 153Professional standards, 153Reimbursement and pricing, 156Outcomes, 159Conclusion, 173References, 175Index, 191

“Despite a rather uninspiring title I found this book to be a fascinating read providing great insight into medicine development and regulation with many interesting examples provided to support the authors views . In my opinion it is actually a lot more balanced and intellectually satisfying than the much higher profile "Bad Pharma" (although that too is also worth reading). I would recommend this book as essential reading for anyone with a professional interest in helping ensure that medicines are used safely in an appropriately governed way and more generally to anyone that is interested in the world of medicine use.”  (Director of Medicines Information at Guy's and St Thomas' Hospital, 29 May 2015)