MAB Registration Exam cheat sheet

Medical Affairs is a non-promotional function spanning Medical Information, MSL/field medical, medical communications, publications, evidence generation, and medical review of promotional and non-promotional material.

Core mandate: scientific exchange and generation/dissemination of fair-balanced, evidence-based information; Medical Affairs does not own sales targets and must remain organizationally separate from commercial incentive structures.

Key deliverables: medical strategy and plans, investigator-initiated study (IIS) programs, advisory boards, publication plans, medical information responses, internal scientific training, and medical/regulatory review of materials.

Medical review decision rule: any material mentioning an unapproved use, a comparator, or a claim not in the approved label requires substantiation by cited evidence and fair balance; unsubstantiated claims are rejected.

Phase of involvement: Medical Affairs input begins in late discovery/early development (target product profile, evidence gap analysis) and continues through launch and lifecycle.

Fair balance rule: promotional material must present efficacy/benefit together with the most serious and most common risks in comparable prominence; Medical Affairs typically reviews for scientific accuracy and balance.

Sunshine/transparency reporting: transfers of value to healthcare professionals and organizations (consulting, advisory boards, meals, travel, grants) are tracked and disclosed under national transparency regimes (e.g., US Open Payments, EFPIA disclosure code).

Distinction rule: Medical Affairs may discuss approved and, where legally permitted, scientific data on unapproved uses in response to unsolicited HCP requests; the commercial team may not proactively promote unapproved uses.

Medical strategy metrics are scientific (evidence gaps closed, publications, IIS milestones, medical information quality), not sales volume.

Standard sequence: discovery and target validation → preclinical (in vitro, in vivo toxicology, PK/ADME) → IND/CTA filing → Phase I (safety, PK, dose) → Phase II (efficacy signal, dose-ranging) → Phase III (confirmatory efficacy/safety vs control) → marketing application → Phase IV.

Typical Phase I enrollment is 20–100 subjects (often healthy volunteers or patients for cytotoxic agents); Phase II is roughly 100–300; Phase III is typically 300–3,000+ depending on indication.

Primary endpoints must be pre-specified; surrogate endpoints (e.g., blood pressure, viral load) are acceptable only when validated or accepted by the regulator for the indication.

Randomization, blinding (single/double/triple), and a concurrent control arm are the design elements that protect against bias; historical controls are acceptable only in narrow, justified circumstances.

Sample size is driven by effect size, variance, alpha (type I error, typically 0.05 two-sided), power (typically 80–90%), and expected dropout; halving the detectable effect size roughly quadruples sample size.

Intention-to-treat (ITT) analysis includes all randomized patients and preserves randomization; per-protocol analysis is supportive and can overstate effect.

Adaptive designs (group sequential, seamless Phase II/III, sample-size re-estimation) require pre-specified rules and control of type I error.

ICH E6 (GCP) governs trial conduct; ICH E8 covers general study considerations; ICH E9 covers statistical principles; ICH M4 covers the Common Technical Document.

Approval pathways: US FDA NDA (505(b)(1)), 505(b)(2) (reliance on prior findings), BLA (biologics), ANDA (generics); EU centralized procedure via EMA/CHMP for new active substances and designated products.

Expedited US designations: Fast Track, Breakthrough Therapy, Priority Review, Accelerated Approval (surrogate endpoint plus confirmatory trial obligation); Orphan Drug designation applies to diseases affecting fewer than 200,000 US patients.

ICH CTD structure: Module 1 (regional administrative), Module 2 (summaries/overviews), Module 3 (quality/Chemistry, Manufacturing and Controls), Module 4 (nonclinical), Module 5 (clinical).

Labeling rule: the approved label defines permitted promotional claims; off-label promotion is prohibited, and company response to unsolicited off-label requests must be handled by Medical Information with approved, fair-balanced standard responses.

Post-approval obligations include periodic safety reports (US PADER/PSUR; EU PSUR with risk-benefit assessment), pharmacovigilance system master file, and risk management/minimization plans (REMS in the US, RMP in the EU).

Change control: variations/supplements are classified by risk (EU: Type IA, Type IB, Type II, and extensions); major changes require prior approval before implementation.

GCP/ICH E6 defines sponsor, investigator, IRB/IEC, and monitor responsibilities; informed consent must be documented before any study procedure.

Inspection readiness: essential documents must be contemporaneous, attributable, legible, original, accurate, and complete (ALCOA+), and retained for the required period (commonly at least 2 years after marketing application approval or study termination, per ICH E6).

Medical Information responds to unsolicited requests from HCPs, patients, and payers; responses must be accurate, balanced, referenced, and approved through the medical review process.

Standard response letters (SRLs) and custom responses must be version-controlled and re-reviewed on a defined cycle or when new safety/efficacy data emerge.

Unapproved-use inquiry rule: respond only to unsolicited requests, in a private/one-to-one setting, with scientific data and no promotional framing; document the request and response.

Fair balance in a medical response: include relevant safety information (boxed/warnings, common adverse reactions) alongside efficacy data.

Reference citation standards: cite primary literature or regulatory documents with full bibliographic detail; avoid citing abstracts, press releases, or unpublished data as sole support for a clinical claim.

Response timelines are governed by internal service levels; triage rules separate adverse event reports and product quality complaints, which must be forwarded to Pharmacovigilance/Quality immediately.

Medical Information is often the entry point for adverse events and special-population questions (pregnancy, lactation, pediatrics, renal/hepatic impairment) where label data may be limited.

MSL role: non-promotional, peer-to-peer scientific exchange with key external experts (KEEs), HCPs, and investigators; MSLs do not sell and do not carry sales quotas.

Compliant MSL activities: responding to unsolicited scientific questions, scientific exchange at advisory boards, supporting IIS concept intake, site support for sponsored trials, and internal medical training.

Prohibited MSL activities: detailing or promoting products, distributing promotional materials, negotiating contracts, providing samples, and proactively discussing unapproved uses.

KEE engagement rules: selection by scientific expertise and publication/clinical-trial record, not prescribing volume; engagements and transfers of value must be documented and disclosed.

Insight collection: MSLs gather scientific insights (unmet needs, data gaps, treatment patterns) and route them through a documented, de-identified process to inform medical strategy; insights must not be used to direct sales targeting.

IIS support: the MSL may discuss the concept and facilitate submission, but the company's medical/independent review committee decides funding and the investigator retains control of design, conduct, and publication.

Field medical documentation must be contemporaneous and stored in the approved CRM; verbal-only agreements and undocumented exchanges are compliance risks.

Cross-functional boundary rule: MSLs may not participate in sales meetings for the purpose of aligning promotional messaging; any commercial interaction must be transparent and non-promotional.

Evidence hierarchy: systematic reviews/meta-analyses and randomized controlled trials provide the strongest causal evidence; observational cohorts and registries provide real-world effectiveness and safety data; case reports are hypothesis-generating only.

Real-world evidence (RWE) sources: electronic health records, claims databases, registries, and patient-reported outcomes; RWE can support label expansion, dosing in special populations, and post-authorization safety studies.

Investigator-initiated studies (IIS): sponsor provides drug/support but the investigator is sponsor-investigator; the company must have a documented review and approval process and track milestones and publications.

Collaborative/company-sponsored post-authorization studies answer questions regulators or payers require: long-term safety, effectiveness in routine practice, and subgroup performance.

Health-economic and outcomes endpoints (quality-adjusted life years, hospitalization rates, adherence, work productivity) are increasingly embedded in Phase III and Phase IV programs to support reimbursement.

Protocol synopsis essentials: objective, design, population with key eligibility criteria, endpoints, sample size rationale, statistical methods, and safety monitoring.

Evidence gap analysis maps the target product profile against available data to prioritize studies; gaps commonly include head-to-head comparisons, special populations, and long-term safety.

Publication and data-sharing obligations: results must be posted on registries (e.g., ClinicalTrials.gov within 12 months of primary completion for applicable trials) and disclosed per company policy and ICMJE recommendations.

Serious adverse event (SAE) definition: death, life-threatening, inpatient hospitalization or prolongation, persistent/significant disability, congenital anomaly, or an important medical event requiring intervention.

Expedited reporting: serious, unexpected suspected adverse reactions (SUSARs) generally require reporting to regulators within 7 calendar days (fatal/life-threatening) or 15 calendar days (other serious) of the sponsor's awareness; follow local requirements.

Causality assessment uses categories such as certain, probable, possible, unlikely, and unrelated (WHO-UMC scale); seriousness and expectedness are assessed independently of causality.

Signal detection combines spontaneous reports, clinical trial data, literature, and real-world databases; disproportionality measures (PRR, ROR, EBGM) are screening tools, not proof of causation.

Aggregate reports: PSUR/PBRER with a benefit-risk evaluation; DSUR annually for investigational drugs; PADER in the US for approved products.

Risk management: risk management plan (EU RMP) or REMS (US) with risk minimization measures such as medication guides, restricted distribution, or pregnancy testing.

Pregnancy and special-population exposures, medication errors, and lack of efficacy reports are collected and evaluated even when not serious.

Good pharmacovigilance practice requires a qualified person for pharmacovigilance (EU QPPV), a validated safety database, and written procedures for intake, triage, and follow-up.

Cost-effectiveness metrics: incremental cost-effectiveness ratio (ICER) = (cost of new − cost of comparator) / (effect of new − effect of comparator); willingness-to-pay thresholds commonly cited are ~$50,000–$150,000 per QALY in the US and £20,000–£30,000 per QALY in England (NICE).

QALY = life years gained × utility weight (0 = death, 1 = perfect health); utility is often derived from EQ-5D.

Budget impact analysis estimates the financial consequence of adoption for a payer over a defined horizon, distinct from cost-effectiveness.

Payer evidence needs: comparative effectiveness, subgroup analyses, real-world adherence/persistence, total cost of care, and budget impact; HTA bodies (NICE, IQWiG/G-BA, HAS, CADTH) apply different evidence standards.

Pricing and reimbursement pathways include value-based agreements, outcome-based contracts, confidential discounts, and patient access schemes.

Outcomes research measures endpoints meaningful to patients and payers: mortality, hospitalization, disease progression, PROs, and caregiver burden.

Formulary decision rule: a product with a higher acquisition cost can still be preferred if total cost of care or outcomes are superior; the comparison must use the relevant local standard of care.

Gift and hospitality rule: transfers of value to HCPs must have a legitimate scientific or educational purpose, be modest, and never be conditioned on prescribing or purchasing; many codes prohibit gifts entirely.

Advisory boards must have a documented scientific need, fair selection of experts, an agenda, minutes, and fair-market-value compensation; attendance by sales personnel is restricted.

Industry codes: IFPMA, EFPIA, PhRMA, and local codes set rules on promotion, interactions with patient organizations, and transparency; compliance is mandatory and audited.

Conflict-of-interest management: disclose financial relationships, recuse from decisions where a conflict exists, and separate medical and commercial governance.

Patient organization interactions must be transparent, documented, and free of influence over the organization's independence; support is disclosed.

Clinical trial ethics derive from the Declaration of Helsinki and the Belmont principles (respect for persons, beneficence, justice); IRB/IEC approval and informed consent are mandatory.

Speak-up and escalation: suspected noncompliance is reported through the compliance hotline; retaliation is prohibited.

ICMJE authorship criteria (all four required): substantial contribution to conception/design or acquisition/analysis/interpretation; drafting or critical revision; final approval of the version to be published; agreement to be accountable for the work.

Ghost authorship (unnamed professional writers) and guest/gift authorship violate ICMJE and industry codes; professional medical writers must be acknowledged with funding disclosed.

Trial registration and results disclosure: registration before first patient enrollment and results posting are conditions for publication in most journals (ICMJE).

Publication plan components: target congresses/journals, timelines, data cut dates, authorship mapping, and gap analyses; the plan is medical-led and not tied to promotional milestones.

CONSORT for randomized trials, PRISMA for systematic reviews, STROBE for observational studies, and CARE for case reports define required reporting elements.

Statistical reporting: report effect estimates with confidence intervals and p-values, pre-specified vs post hoc analyses, and absolute as well as relative measures.

Journal selection considers scope, impact factor, open-access cost, and audience (clinical vs health-economic vs specialty); predatory journals are excluded by standard checks.

Authorship disputes and data integrity issues are escalated to the medical/legal review and handled per COPE guidance; retraction is reserved for serious misconduct or invalid findings.