Clinical Pharmacology - Regulation, Introduction and Monitoring of Medicines

Question 1

Who is going to be interested in your healthcare/prescribing?

Answer 1

• Public
• MPs (if you are a democracy)
• Industry
• Doctors/Pharmacists
• Media

Question 2

You are dictator-for-life!

How are you going to Structure your health Care system?

what questions do you need to think about?

Answer 2

Who is going to be interested in your healthcare/ prescribing?

Who will you allow to prescribe?

Can your prescribers prescribe whatever they want to prescribe?

Question 3

Drug companies have hiked _____ exorbitantly over the past several years

Answer 3

prices

Generic drugs should be cheaper once patent ends

Mylan pharmaceuticals: 548% increase in price of EpiPen

Isuprel and Nitropress: Valeant Pharmaceuticals increased costs of:

• Isuprel: $180 to $1,472 a vial, a 718 percent increase.
• Nitropress ($215 a vial to $881) a 300% increase

Valeant: bought ‘old’ drugs and increased their prices precipitously

Question 4

how has spending on presciption drugs changed?

Answer 4

Number of drugs being prescribed for older people or more conditions is increased

Question 5

what is the price difference of drugs like between he US and UK?

Answer 5

Same drug in us cost much more than it would in Europe and uk

Another drug showing the difference in price in the UK and Switzerland compared to the US

Question 6

Pharmaceutical advertising - Direct to consumer advertising - what is it?

Answer 6

the pahrma companies advertising directly to comsumers

very expensive

Only 2 countries you can advertise direct to the consumers in the US and New Zealand

Question 7

Pharma direct to consumer advertising - what are the advantages?

Answer 7

Empowers patients

Disease education

Prompts patients to seek more timely medical advice and support

May result in earlier diagnosis and treatment

May improve adherence

Question 8

Pharma direct to consumer advertising - what are the disadvantages?

Answer 8

Consumers think it increases prices (Consumers think it increases price as the 5.4 billion dollars has to be paid somewhere)

Reduces authority of the doctor (as patient more empowered)

Inflates demand for new/expensive drugs even if not appropriate

Off patent use (eg surgical glue)

Question 9

Advertising to doctors:

Things are now very ________ regulated in the UK in terms of the amount of advertising and promotion that companies can do to your _______ professionals

Answer 9

tightly

medical

Question 10

what are the statistics for prescribing in scotland? (2011-2012)

Answer 10

Total spend on the NHS is up to around 13 billion which is the same as the deficit

Question 11

With all new drugs being considered for use in the general population you need to know what?

Answer 11

• Does it work?
• What dose is therapeutic?
• What dose is toxic?
• Is it safe?
• Is it necessary?

Question 12

Who regulates drugs/devices in the UK?

Answer 12

Commission on Human Medicines (CHM)

Formerly Committee for Safety of Medicines (CSM)

Question 13

what do Commission on Human Medicines (CHM) do?

Answer 13

Advises Ministers on matters relating to human medicinal products

Advises Licensing Authority (LA)

Considers representations by an applicant or MA (Marketing authorisation) holder

Promotes collection and investigation of information relating to adverse Drug Reactions to human medicines.

Question 14

CMH sits within a bigger organisation called the MHRA

Medicines & Healthcare products Regulatory Agency (MHRA) –Executive Agency of DoH

what is their role?

Answer 14

Post-marketing surveillance – ADRs and incidents

Assessment & Authorisation of medicinal products for sale in UK

Devices

Quality control

Internet sales & counterfeiting (drugs coming to the UK that are made elsewhere)

Clinical Trials regulation

Statutory controls

Promotion of safe use

Manage British Pharmacopoeia & Clinical Practice Research Database

They will ask for a report of the first prescriptions of the drug to see how its been

Question 15

Why is pharmacovigilance needed?

Answer 15

Rarer the side effects may not be identified in the RCT

So you do need post marketing surveillance of a drug to see how it is doing once it has came into the world

Question 16

how do you report an ADR?

Answer 16

yellow card scheme

Question 17

Where have all the yellow card reports came from?

Answer 17

Need to be looked at to see if they are truly related to the drug or if they are part of a wider sickness profile of the patient

Question 18

how does the yellow card shceme work?

Answer 18

Question 19

How do you know when a signal is significant?

Answer 19

Question 20

•Another role is monitoring drug ___________, ________ of the drug

Careful regulation of where did the drug ____ ____, what is it, and does it do what it _____ on the tin

Answer 20

production

standard

come from

says

Question 21

what is the European Medicines Agency? and what is their role?

Answer 21

European equivalent of FDA (food & drug administration in the US)

Ensure quality, safety and efficacy of drug

Marketing Authorisation (MA) or License Valid for whole of EU

Committee for Medicinal Products for Human Use (CHMP):

• Quality
• Safety
• Efficacy

Question 22

Once drugs are on the ______, companies can ______ whatever the market will ____; prices for cancer therapies now routinely top $100,000 a year.

Answer 22

market

charge

bear

Question 23

So who decides whether a drug can be used?

(In the US, insurance companies)

Answer 23

Scottish Medicines Consortium (SMC)

Question 24

what is the role of the Scottish Medicines Consortium (SMC)?

Answer 24

Principal remit is to make decisions on the cost effectiveness of new/existing pharmaceutical products in respect of their use in NHS Scotland

They will all get together and discuss and look at the evidence for the specific drug and decide if it should be available for the general population in Scotland

Question 25

who makes up the Scottish Medicines Consortium (SMC)?

Answer 25

Representation from all Area Drugs and Therapeutics Committees: - Pharmacists - Health economists - Pharma representatives - Lay representatives - Physicians - NHS management

Question 26

whata re the good things about the SMC?

Answer 26

comprehensive assessment (of new drugs) rapid response uniformity within Scotland minimise “post code prescribing” education

Question 27

what are the threats of the SMC?

Answer 27

pharmaceutical freedom funding

Question 28

what do SMC do with submissions?

Answer 28

3 month assessment process at time of launch Submission by manufacturer Health economic analysis Cost per QALY (quality adjusted life years) central Attempt to be fair and reasonable Problem with very expensive drugs – Political overtones

Question 29

what are the 3 different outcomes from the SMC?

Answer 29

* Approved for use * Approved for restricted use * Not recommended

Question 30

why may a drug by not recommened by the SMC?

Answer 30

* Clinical effectiveness not convincing * Cost-effectiveness not demonstrated * No submission by manufacturer * Phamasuticals are allowed to: * Resubmission * Appeal * Individual Patient Treatment Requests (IPTRs) – if a particular consultant wants a drug for a patient

Question 31

Cycstic fibrosis: Life-threatening, Childhood onset, Caused by mutation in cystic fibrosis transmembrane regulator (CFTR) G551D-CFTR occurs in ~12% cases in Scotland Ivacaftor selectively potentiates CFTR in those with G551D mutation Two key studies to date - Aged 6-11 years and 12+ Both showed 10% improvement in FEV1 Some improvement in respiratory symptoms and weight Not clear how/if this translates into survival Substantial extrapolation

Answer 31

"Not recommended” Weakness of economic case Balance of cost/benefit unfavourable veyr expensive “Not recommended” advice from SMC Huge publicity in National Press Politically unacceptable Scottish Government overruled SMC by setting up an “Rare Conditions Medicines Fund” (RCMF) to facilitate provision of ivacaftor to CF patients with G551D-CFTR mutation (£25M) Review of SMC processes

Question 32

Enhancing access to new medicines: what is an end of life medicine?

Answer 32

“A medicine used to treat a condition at a stage that usually leads to death within 3 years with currently available treatments.”

Question 33

Enhancing access to new medicines: what are orphan and ulta-orphan medicines?

Answer 33

Orphan medicines - “A medicine with EMA designated orphan status (ie conditions affecting fewer than 2,500 people in a population of 5 million) or a medicine used to treat an equivalent size of population irrespective of whether It has designated orphan status.” Ultra-orphan medicines - “A medicine used to treat a condition with a prevalence of 1 in 50,000 or less (or around 100 people in Scotland.”

Question 34

what are the challanges of enhancing access to new medicine

Answer 34

Company engagement – expected to improve Current QALY “threshold” may already be over generous (£13,000 per QALY may be more appropriate) Incentive to propose PAS may be reduced Net budget impact in year 1 may be £70M Equivalent changes in England & Wales may have inflated drugs budget by an estimated 7.5%

Question 35

Area Drugs & Therapeutics Committees - what is their role?

Answer 35

Response to SMC appraisal “Approved for use” - Expected to approve for local use, unless equally effective alternative available locally. (“Me too” scenario). Local preference taken into account. Cost may be a consideration “Not recommended” - Default position is not to approve for local use, IPTR may apply (individual patient treatment requests)

Question 36

Why local Formularies?

Answer 36

* Local ownership of decisions * (but much common ground in Scotland) * familiarity with limited range * effectiveness * value * primary/secondary care issues * new technology - intranet/websites, hyperlinks to guidelines * electronic prescribing - GPASS, EMIS, Vision etc

Question 37

what is the role of ADTCs?

Answer 37

* development of regional formularies * implementation of SMC advice * implementation of NICE/QIS appraisals * implementation of SIGN guidelines * dealing with drugs not on SMC agenda * dealing with unlicensed products * rationing new and expensive drugs * regional “shared care/interface” issues * education & communication * prescribing errors * “out of line” prescribers * antimicrobial policies * Patient Group Directives

Question 38

disinvestment - Recommend removal from Grampian Joint Formulary why may this happen?

Answer 38

[a] evidence for superior efficacy/safety/kinetics now available for alternative product [b] evidence from major outcome studies now favour an alternative product [c] evidence of superior cost/benefit now available for an alternative product [d] evidence that this product is of limited clinical effectiveness