Development of Publications forProactive and Reactive Distribution

to Health Care ProfessionalsJeffrey E Fletcher PhD, Senior Clinical Publications Lead

Danielle Titus PharmD, Senior Medical Information Manager,Christopher Norenberg, Director Promotional Regulatory Affairs

Kevin Krause, Senior Therapeutic Brand LeaderAstraZeneca

Learning objectives

Following this presentation the attendee should:

Understand how publications in the scientificliterature or presented at scientific congressescan be used by the brand team in theirinteractions with health care professionals

Understand the differences between proactiveand reactive distribution of publications

Know which regulations cover proactive andreactive distribution of publications in the US

Know how to develop publications that best meetthe needs of the brand team

Proactive distribution ofon-label information

Distribution by sales force

Promotional activity regulated by Division of DrugMarketing, Advertising and Communication(DDMAC) 21 CFR 202.1

Must be on-label

Peer-reviewed, good science, not misleading

Must contain proper disclosures (eg, includes anoff-label dosage)

Must provide fair balance (cannot only provideefficacy information, must provide safety)

Must be accompanied by package insert

No DDMAC review required

Physician information request

Not a promotional activity, unsolicited request forspecific information

Regulated, not regularly reviewed, by DDMAC• Must be scientifically accurate, representing the

complete body of knowledge to answer question• Full “fair balance” not required in the same manner as

promotional material

On-label or off-label information

Above must be accompanied by package insert

Investigational drug information• No efficacy or safety claims• Only results

Scientific exchange

Not a promotional activity

Examples:• Publication of clinical study in a journal• Poster/slide presentations in scientific sessions• Field medical information scientist discussion with HCP

On-label or off-label information

Conclusions should not over interpret results, orotherwise be misleading

Off-label informationdissemination

Regulated by DDMAC (21 CFR 99) Food & DrugAdministration Modernization Act (FDAMA) 1997

New use of approved product, not unapproved drugDissemination of scientifically-sound peer-reviewedreprints (unabridged, full article) under specifiedconditions (proper disclosure), sNDA submitted within3 years (development plan submitted)

Must be no risk to public health, not false or misleadingThere can be no association with promotional material

No abstracts or letters to the editor, or supplementsfunded by manufacturers

Can include health economic information to formularycommittees

Must submit to DDMAC 60 days prior to dissemination!Must submit to DDMAC 60 days prior to dissemination!

Use of publications with healthcare professionals

Promotional dissemination (proactive)

Sales force

Scientific dissemination (reactive)

Field medical directors

Field medical information scientists

Medical information managers (eg,physician information requests)

Managed care dossier

Publications used promotionally

GeneralIndication/use and dose consistent with label• Should not mention off-label use in discussion• Can have disclaimer accompanying article for

some off-label information (eg, additional doseoutside label)

Published in peer-reviewed journal

Publications used promotionally

Study designProspectively planned

Appropriate selection methods for patients

Randomized and single- or double-blindstudy

Well-described treatment regimen with cleardescription of dose, schedule, duration, androute of administration

Appropriate control (active or placebo)

Publications used promotionally

MethodsPredefined methods used for assessing subjectresponse (well defined, reliable, and validated)

Analytical methods appropriate for detecting drugeffect

Sample size adequate

Adverse events collected and reported

Qualifications defined for dose reduction andtreatment interruptions due to toxicity

All enrolled patients accounted for, including allwithdrawals

Publications used promotionally

Endpoints and statisticsClinically meaningful endpoints orappropriate surrogate• Reasonably likely to predict efficacy and safety

Primary and secondary objectives stated

Analyzed in scientifically appropriate manner

Statistical significance indicated

Primary endpoints met

Publications used promotionally

Head-to-head studiesDose consistent with label for both products

Indication consistent with label for bothproducts

Dose is similar between treatment groups(low dose to low dose, and high dose to highdose)

Products are in same therapeutic class

Publications used promotionally

Study performed according to Good ClinicalPractice (GCP):Qualified investigatorsIRB approval and oversight

Written informed consent obtained

Compliance with protocol

Appropriate data collection and reporting

Study is monitored

In accordance with Declaration of Helsinki

Publications used for scientificdissemination

Should meet all of the previously statedrequirements for promotional use,except:Can disseminate reactively if indication/useor dose not consistent with label

Conclusion

Engage promotional regulatory affairsduring manuscript development

Proactively ensure publication meetsinternal and external guidelines tooptimize distribution of publications bysales force

Establish a best practice checklist

Off-the-cuff discussion

How important are publications in youractivities?What publications can you use (abstract,posters, slide sets)?How do you handle “fair balance” in your useof publications?

What is your frequency of off-label informationuse and restrictions/precautions associatedwith its use?

What do you look for in publications to meetyour needs?

Q & A

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