Objectives Provide PAAB code advice in response to

Objectives • Provide PAAB code advice in response to proposed campaign plans. • Make rulings about whether specific activities and/or messages are aligned with the code (emphasis on digital). • You’ll flex your evidence requirement muscles to make rulings about whether presented references are appropriate for the proposed codes.

PAAB 401 Patrick Massad Deputy Commissioner, PAAB patrickm@paab. ca November 2014

Afternoon Main Topics • Building compliant campaigns across both digital and traditional media • Ensuring there is a fair balance between risk in benefits in advertising • Submitting claims reflecting the evidence standards in the PAAB code and guidances

Corrazon® (50 mg Babugatran tablet) • Rx anticoagulant • Indicated for prevention of stroke in patients with atrial fibrillation • Key safety considerations: Bleeding and diarrhea • 1 tablet BID regardless of kidney or liver status • Don’t take within 1 hour of milk product consumption • Market leader (TRx data) • Winner of MMEA for the Canadian television ad “Tu ares mi Corrazon” (i. e. Massad Marketing Excellence Award)

Gorilza® (100 mg Babugatran) • Pretty much Corrazon in a once daily pill (thanks to our patented Chepeziac Controlled Release Matrix®) • It’s in the same PM as Corrazon but it has its own pivotal trials and a separate Part III section • Canada is the first country in the world to launch it • Available since Nov 1, 2014.

Key Branding Images Corrazon Spokesperson for Corrazon Gorilza

Exercise 1. Conceptualize a website Keep in mind that PAAB Pharma Inc wants a single website: – For both products AND – Disease info in two formats • One written for the 6 th grade level • One written using language and content appropriate for clinicians At least one person per table should neatly map out a highlevel description of the structure of your website. Specifically…

i. e. create something like this…

Specifically… • On a conceptual level, determine the site’s structure – Map out where general types of information would go (e. g. “Corrazon Claims”, “Disease info”, “Safety Info” for both products in all audiences). • What is the landing page url? • Identify outgoing links (e. g. corporate website) • If applicable, where/which gating mechanisms will be employed • Identify which segments will be coded with a “no index” command • Describe any links on your landing page. The manufacturer has a lengthy legal page on the corporate website for privacy. Don’t worry about SEO and SEM and incoming links yet. That will come soon. 15 min

URL www. strokepreventionatpaabpharma. ca No-index command used on all pages following a gating mechanism Since homepage is not branded, it can link to corporate site home page. 5 min

Exercise 1 part Deux Where appropriate, include instructions related to meta data. 5 min

Switching gears. For now… Forget about the combined website. For the website, www. corrazon. ca your boss wants you to get the following SEM keywords approved by PAAB. Do you need to manage her expectations for any of the following? a. The word “Corrazon” b. The word “Corrazone” c. The word “Corrazoon” d. The word “Pradaxi” e. Study names (both pivotal and ongoing) e. g. Raj study. f. The keyword phrase “side effects” g. The word “Bleeding” h. The word “Efficacy” i. The Broad Match Key Word “Corrazon” j. The keyword phrase “Two dogs rowing” 5 min

Let’s add UGC functionality to our combined site. Is intervention necessary in the following cases? If so, how are you intervening? a. Patient portal: “I took my Corrazon with me when I visited the capital of Canada, Toronto”. b. Patient portal: “I experienced severe skin discoloration while on Corrazon” [There is no mention of this effect in the product monograph] c. Patient portal: “I take my tablet with a glass of milk. I have not had diarrhea since starting this”. d. Public section: “Corrazon sucks. My doctor put me on it to prevent a stroke. Well, I’ll tell you one thing, it succeeded in preventing me from having enough cash to buy my Viagra. ” 5 min

Which of these scenarios require monitoring? a. PAAB Pharma Inc purchases Corrazon Facebook banner ads. Do the walls and timelines the ad appears next to need to be monitored by PAAB Pharma Inc? b. How about comments in an app description for PAAB Pharma Inc’s unbranded app on A. Fib? c. How about comments in response to a You. Tube video for the Corrazon TV commercial posted by Sexy. Saskatoon. Man. User 4723? d. How about posts on a Corrazon Face. Book page created by PAAB Pharma Inc? e. The Taco Bell dog is a spokesperson for Corrazon. Might PAAB Pharma Inc be responsible for tweets from his personal Twitter account? 5 min

Apps!! You’ll be doing internal training on PAAB requirements for app descriptions accessible in the apple store. Write down all elements the PAAB will need to review and note one or two important regulatory pointers to keep in mind for each element. 5 min

Question What changes if the app is going to only be available from the website we created?

Fair Balance

HCP rotating banner ad 1. Draw a single banner ad (with multiple frame) for both Gorilza and Corrazon which highlights the following elements: – Item 1. The statement “Corrazon is the # 1 dispensed anticoagulant by cardiologists”[referenced appropriately to IMS Brogan Compuscript] – Item 2. Two cartoon Rx Pads. One with the text “Corrazon 50 mg BID”, the other with the text “Gorilza 100 mg OD”. – Item 3. The PM statement “Not metabolized in kidney or in liver” – Item 4. The statement “CCS recommends Babugatran as a first line agent for prevention of stroke in atrial fibrillation patients”[reference to the 2012 Canadian Cardiovascular Society guidelines] – Item 5. The statement “Corrazon and Gorilza are indicated for the prevention of stroke in patients with atrial fibrillation” – Item 6. Designate an area on the banner which will contain the balance level. What level of FB are you using? Where will the indication appear? Given only what you know for sure, is there a problem with one of the items. 5 min

Identify all ways you could meet highest level FB requirements Corrazon reprint holder 5 min

Identify all ways you could meet highest level FB requirements Gorilza Tent Card 5 min

What level of FB is required based on visible content? • A two sided card containing only information describing the ongoing Raj study. Here is one of the two sides: RAJ Trial Landmark Study In DVT Prevention Endpoint: • Primary: Lorem ipsum dolor sit amet, consectetur • Secondary: sed do eiusmod tempor incididunt ut Will be the largest study in DVT prevention (n=7000) Start date: Feb 2012 www. corrazon. ca End date: March 2015 • By the way, do any issues jump out? • Can we add this study to our website when published? 5 min

Evidence

Recall this claim which PAAB Pharma Inc wanted? ? • “Gorilza is Corrazon in a once daily dosing format”. • “Gorilza offers the efficacy and safety of Corrazon in a once daily dosing format”. • “Gorilza demonstrated similar efficacy and safety to Corrazon. Gorilza is dosed once daily”. • Gorilza is babugatran in a once daily dose

Please approve this tiny unsolicited change indicated by use of red font Babugatran 5 years of use in Canada: • 50, 000 patient years of use • Gorilza is babugatran in a once daily dose

Can we make the claim “Celebrex has a lower incidence of abdominal pain vs Diclofenac”? Compromise: How about “Celebrex has a 4. 1% incidence of abdominal pain vs 9% for Diclofenac”?

Exercise 2: See table 25 (ONLY table 25 for now) You are the reviewer. PAAB Pharma submitted the following presentation referenced to Table 25 of the Xarelto PM: Total Stroke and Systemic Embolism: Xarelto demonstrated reduction vs Warfarin (1. 7%/yr vs 2. 15%/yr respectively, p=0. 015)* That’s only part of the piece, but it’s the entire segment relating to table 25. Any changes required? 5 min

Exercise 2 continued: See table 4 (ONLY table 4 for now) You are the reviewer. PAAB Pharma submitted the following presentation referenced to Table 4 of the Xarelto PM: Demonstrated Efficacy: • Lower rate of intracranial hemorrhage vs warfarin (0. 49%/yr vs 0. 79%/yr, p=0. 019)* That’s only part of the piece, but it’s the entire segment relating to table 4. Any changes required? 5 min

Say table 4 was based on an interim analysis and updated data is now available. When can the APS be revised to include the updated data?

Exercise 2 continued: See table 2 (ONLY table 2 for now) You are the reviewer. PAAB Pharma submitted the following presentation referenced to Table 2 of the Pradaxa (dabigatran) PM: Safety Profile: • Similar incidence of adverse events vs warfarin (72. 0% vs 70. 8% p=NS)* That’s only part of the piece, but it’s the entire segment relating to table 2. Any changes required? 5 min

e. Detailing: Clicking on an icon next to the claim reveals… Scenario 1 Scenario 2 Linkage assessed Reviewed as though it were APS copy

Hypothetical Survey Question “Imagine that there was a Corrazon patch on the market that was as at least as effective but safer than warfarin, Pradaxi, and Eliquist. Would you like to try that patch? ” A. Fib Patients Cardiologists No 28% No 26% Yes 74% Yes 72% Yes No

“If your anticoagulant therapy entailed replacing a patch once per week, how likely are you to adhere to your anticoagulant therapy? ” 70% 65% 60% 50% 40% 30% 25% 20% 10% 0% Not likely Somewhat likely Very likely

Global Creative: With Gorilza, stroke prevention takes less than 10 seconds per day Gorilza Once daily dosing

Merci