Why this drug is a high‑scrutiny case.
Asfotase alfa treats hypophosphatasia (HPP) with weight‑based subcutaneous dosing (commonly 2 mg/kg three times weekly—or 1 mg/kg six times weekly—with potential escalation to 3 mg/kg three times weekly for inadequate response). Pediatric‑onset criteria, specialist involvement, and maintenance supply through specialty pharmacy make it clinically essential and financially material to monitor use. When mg/kg scales with weight, even modest documentation errors—or intentional manipulation—can push annual cost into seven figures. That combination demands tight provenance at every step.
1) Intake & eligibility: set the audit trail
What to capture
- Member identity, coverage line (Commercial, Exchange, Medicare/Medicaid where applicable), effective dates.
- Treating prescriber NPI, specialty, and care setting (endocrinology, genetics, metabolic disorders, or equivalent).
- Initial request type (new start vs continuation) and requested regimen (mg/kg, frequency, days’ supply, vial strengths).
Controls & red flags
- Control: Require a single point‑of‑contact prescriber for long‑term management (to avoid fragmented orders). This is a similar approach to State-run prescriber lock-in programs for Medicaid
- Red flags: Multiple concurrent prescribers; ambiguous line of business; mismatch between prescriber specialty and disorder complexity.
2) Diagnosis provenance: prove HPP and onset
Policies for HPP commonly accept one of several evidentiary anchors for diagnosis, then add clinical context and onset timing.
What to capture (one or more)
- Genetic evidence: Pathogenic ALPL variant report with patient name/DOB and lab identity.
- Biochemical evidence: Persistent low serum alkaline phosphatase (ALP) appropriate for age/sex or elevated ALP substrates (e.g., pyridoxal‑5′‑phosphate [PLP], inorganic pyrophosphate, urinary phosphoethanolamine).
- Clinical manifestations: Charted history consistent with pediatric‑onset HPP (e.g., skeletal abnormalities, early tooth loss, failure to thrive, B₆‑dependent seizures, respiratory problems).
Onset verification
- Documentation that signs/symptoms began ≤ 18 years, with dated notes (birth/neonatal, pediatric dentistry, growth charts, imaging). The “diagnosed at birth” line often travels unchallenged—time‑stamped source notes matter.
Controls & red flags
- Control: Keep exact PDFs of lab/genetic reports and hash them (or otherwise fingerprint) to detect reuse across different members.
- Red flags: Generic “family history” with no patient‑specific evidence; undated or redacted lab screenshots; reports whose metadata doesn’t match the patient or test lab; identical lab PDFs reused in multiple cases, or narrative change over time
3) Clinical severity & prescriber credentials: intent and capability
What to capture
- Specialist attribution (genetics/endocrine/metabolic) and consultation note. This can be a verified NPI list.
- Baseline severity summary (skeletal manifestations, respiratory/feeding issues, pain/function metrics).
- Care plan indicating dose, frequency, training for administration, and follow‑up labs.
Controls & red flags
- Control: Require the initial consult to explicitly state the indication (perinatal/infantile vs juvenile onset) and intended mg/kg rationale.
- Red flags: Non‑specialist prescribers initiating therapy without consult; templated notes that repeat generic language across patients.
4) Weight‑based dosing math: the most exploited variable
Because dosing scales with kg, weight is the easiest lever to distort—intentionally or accidentally.
What to capture
- Current weight in kilograms from the most recent clinical visit (e.g., within 30–60 days of the fill), with date/time and source.
- Regimen requested (e.g., 2 mg/kg * 3/week vs 1 mg/kg * 6/week; and any escalation to 3 mg/kg * 3/week with justification).
- Vial strengths and quantity calculation (show your work): total mg per 28–30 days, number of vials, rounding logic, and wastage assumptions.
Quick check math (for auditors)
- Weekly mg at 2 mg/kg * 3/week = 6 mg/kg/week × current weight (kg).
- Monthly mg ≈ 4 × weekly. Compare to billed mg (from NDC strength × quantity).
- If escalation to 3 mg/kg * 3/week, weekly mg = 9 mg/kg/week; require documented insufficient response pre‑escalation.
Controls & red flags
- Controls:
- Policy that re‑verifies weight at defined intervals (e.g., every 1–2 months for pediatrics; quarterly for stable adults).
- Packaging guardrail for pediatric patients below certain weights (e.g., avoid high‑strength single vials when label cautions apply).
- Red flags:
- Weight values that don’t trend with growth charts (or rise implausibly fast).
- Sudden step‑up in vials dispensed without a corresponding escalation note.
- Repeated “lost/damaged” shipments followed by early refills.
- Dose requests that exceed label‑consistent mg/kg without documentation.
5) Prior authorization (PA): translate text to rules
What to capture
- Evidence set used to answer PA prompts (diagnosis proof, onset timing, specialist involvement, weight, baseline labs).
- Decision explanation (approved/denied) with criteria lines referenced and effective dates of the policy version.
- If approved for escalation dosing, the insufficient response evidence (functional, radiographic, or lab surrogate/biomarker).
Controls & red flags
- Control: Maintain a traceability table that maps each PA question to the source clause in policy and to the document that satisfied it.
- Red flags:
- PA packages where different members present the same PDF hash for labs/notes.
- “Diagnosis at birth” with no pediatric records surfaced.
- Specialist box checked but prescriber is not a specialist (or consult note absent).
6) Specialty dispensing & cold chain: custody and quantity integrity
What to capture
- NDC, strength, lot/expiry (when available), quantity, days’ supply, and frequency instructions.
- Cold‑chain documentation and proof of delivery (signature, timestamp, ship‑to address).
- Nurse/patient training logs for administration (first shipment) where applicable.
Controls & red flags
- Controls: Require delivery to patient residence (or documented clinical ship‑to) and deny third‑party forwarding addresses.
- Red flags:
- Quantity not divisible by labeled vial strengths given the dose math.
- Repeated address changes or requests to ship to work/temporary locations.
- Multiple active open shipments for the same member.
7) Claim adjudication: the data must reconcile
What to capture (NCPDP fields & context)
- Product/Service ID (NDC), Quantity Dispensed, Days’ Supply, DAW, Prescriber NPI, Prior Auth Number, Pharmacy NPI, Ingredient Cost, Copay/Coins, Compound code = N.
- Internal computation of expected quantity from (member weight × mg/kg × frequency × days) / vial mg, adjusted for rounding rules.
Controls & red flags
- Controls:
- Real‑time check that expected quantity ≈ billed quantity within tolerance (this can be teased 5 or 10%, especially if only a few commercially available dose/strengths.
- Block on mg/kg above policy cap unless an exception record is attached.
- Red flags:
- Over‑fills vs expected quantity without dose change.
- DAW/LAS switches that inflate spend without clinical reason.
- Multiple pharmacies billing for the same member/month.
8) Refill cadence & adherence: early refills are a signal
What to capture
- Next fill date from days’ supply; patient‑reported on‑hand inventory; administration diary (if collected).
- Any returns/credits for temperature excursions or missed doses.
Controls & red flags
- Controls: Set early refill thresholds (e.g., ≥ 85–90% of expected use probably best for specialty drugs) and require pharmacist outreach before override.
- Red flags: Serial early refills; repeated reports of damaged product; dose escalations that coincide with weight increases without corroborating clinical need.
9) Re‑authorization (typically at 6–12 months): demand outcome evidence
What to capture
- Updated weight and current regimen; adverse events; adherence summary.
- Outcome signals appropriate to onset/type (growth, mobility/pain reports, respiratory function, fracture frequency, or other clinician‑documented benefits).
- Rationale for continuation or de‑escalation; plan for monitoring.
Controls & red flags
- Control: Require at least one objective measure (lab, imaging summary, standardized assessment) in addition to narrative notes.
- Red flags: Static copy‑paste re‑auth letters; escalating dose with no documented benefit; no evidence of specialist follow‑up.
10) Post‑pay analytics: pattern hunting without hindsight bias
Signals to monitor (examples)
- Spend outliers: per‑patient annual cost > peer decile after adjusting for weight and frequency. (depends on how big your covered lives # is)
- Document reuse: identical lab or letter hashes across different members or providers.
- Prescriber density: one prescriber accounting for a disproportionate share of approvals.
- Pharmacy concentration: one pharmacy NPI with a cluster of early refills/over‑fills (unless an exclusive LDD, then that is another challenge)
What to do with hits
- Trigger targeted audits that re‑request primary documents (not screenshots), confirm recent weights, and reconcile billed mg to regimen math.
- If systemic: review policy language for ambiguities that are being interpreted inconsistently, and tighten question prompts.
11) Communications & fairness
- Be explicit that audits aim to protect appropriate access and safeguard program integrity, not to penalize genuine patients.
- Offer a clear appeals path and what evidence shortens appeals (e.g., the exact pediatric records that verify onset; original genetic lab PDFs).
- Close the loop by updating policies and PA question sets when a recurring ambiguity is discovered.
Quick reference: materials to request at each stage
- Diagnosis & onset: ALPL genetic report or ALP/PLP labs; pediatric notes/dental records/imaging with dates; specialist consult.
- Dosing math: most recent weight (date/time), regimen (mg/kg & frequency), vial strengths, month‑over‑month quantity calculation.
- Dispense/ship: NDC/lot/expiry (if available), quantity, days’ supply, cold‑chain logs, proof of delivery.
- Claims: NCPDP fields, prior auth reference, ingredient cost, copay/coinsurance.
- Continuations: updated weight, outcomes, adherence, rationale for any escalation.
- Analytics: member‑level spend trend, document hashes, prescriber/pharmacy concentration, early refill rate, growth‑curve plausibility.
Closing
For a therapy like asfotase alfa (Strensiq)—life-altering for the right patient and extraordinarily costly—provenance is paramount. When every artifact (diagnosis, onset, mg/kg math, shipment, claim, outcome) is captured with dates and document fingerprints, the “holes” in your Swiss‑cheese model stop lining up. The result is the same goal every stakeholder shares: patients who qualify get treated quickly, equitably and programs remain credible and sustainable for the long run.
