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Off-label Prescribing: Justifying Unapproved Medicine



Off-label Prescribing: Justifying Unapproved Medicine

David Cavalla

ISBN: 978-1-118-91207-2 March 2015 Wiley-Blackwell 216 Pages


Today’s medicines are regulated for their efficacy and safety and, once approved, they can be marketed for certain uses as justified by the data. Regulatory bodies in developed countries are constituted by legal statute and operate as parts of government, ostensibly in the interests of the people as patients.

But once approved, medicines can be used for any purpose the prescriber thinks fit and appropriate for the patient. One in five prescriptions is therefore written outside regulatory purview.

Off-label Prescribing looks into the corners of our medicated lives, where drug regulation runs up against medical practice, and concerns the use of a drug that has been approved for one use (in medical parlance, ‘indication’) being used for a different indication; alternatively, being used on a different set of patients from the ones it is approved for, or at a different dose. Usually the patient is unaware of what is going on, having not been informed by their doctor of this aspect of his or her prescribing choice.

The book examines how and why this occurs, what the various medical professions have to say about it, and how pharmaceutical companies benefit by moving into this poorly regulated area. Off-label Prescribing pulls these complex issues together in one volume, to highlight current practice, its advantages and weaknesses and how the author suggests practice should evolve in the future. It will therefore be of interest to all those who prescribe (and receive) medicines, combined with a greater objective to provide more transparency and discussion for professionals.

Foreword, ix

Acknowledgement, xi

Author’s note on the cover design, xiii

Introduction, xv

1 What is off-label medication, and how prevalent is it?, 1

What is ‘off-label’ medicine?, 2

Scope of the issue, 8

2 Where it all went right: new uses for existing drugs supported by good evidence, 19

Examples where products have been through regulatory approval for a secondary use, 19

Finasteride: pseudohermaphroditism and hair growth, 19

Sildenafil: re-tasking the blue pill for a life-threatening illness, 21

Doxycycline: from killing bugs to protecting gums, 22

Raloxifene: from cancer to bone disease and back again, 23

Galantamine: using snowdrops to improve memory, 24

Cyclosporine: preventing immune attack on organs and skin, 25

Dimethyl fumarate: a remarkable drug for multiple sclerosis, 26

Botox: a drug to kill or cure you, 27

Examples where evidence is uncertain and not to regulatory standards, 28

Tricyclic antidepressants: for curing more than emotional pain, 28

Aspirin for cancer, 30

Retrospective data: looking back to create future therapies, 30

3 Shared decision making and consent, 33

Viewpoint of the patient, 34

Viewpoint of the prescriber, 37

Professional guidelines, 38

Patient awareness, 41

Practitioner attitudes, 41

Diagnosis, 44

4 Gaming the system: the role of the pharmaceutical industry, 47

Normal drug development and drug repurposing development, 48

Gaming the system, 53

Orphan use, 56

Pharmaceutical marketing, 61

Expanding uses for non-pharmaceuticals, 64

DTC advertising, 64

Patents and genericisation, 65

Conclusion, 68

5 Do no harm: Safety and efficacy, 71

Relative safety, 73

Different therapeutic uses, 73

Chronic versus acute dosing, 78

Different dose, 81

Differences between children and adults, 82

Other patient populations, 86

Fatal ADRs, 87

Quality of evidence, 88

Strong evidence, 89

Poor evidence, 91

Doctors do not know evidence, 94

Proximity of off-label to on-label, 96

Debunking medical myths, 101

6 Liability, injustice and reimbursement: who should pay?, 105

A prescriber’s ethical and professional duties, 105

Medical professional participation in off-label promotion, 105

A prescriber’s legal position, 106

Consent, 106

Liability, 111

Reimbursement, 113

Compendia, 115

NICE, 117

Compassionate access, 120

Cost, as a driver for off-label medicine, 121

7 The role of regulation in off-label medicine, 125

Regulators do not regulate medical practice, 126

Off-label marketing, 128

Off-label fines, 130

Whistle-blowers, 134

European situation, 134

Tip of the iceberg, 136

Free speech, 138

8 Justifying unapproved medicine, 143

Constraints on making changes, 144

Moves to enhance off-label medicine, 145

Diagnosis shifting, 146

A partial solution: clinical trial transparency, 147

A solution based on increased regulatory supervision, 152

My solutions, 153

Professional standards, 153

Reimbursement and pricing, 156

Outcomes, 159

Conclusion, 173

References, 175

Index, 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)