Section I of the Centers for Medicare & Medicaid Services (CMS) Negotiation Data Elements Information Collection Request (ICR) is the form through which a manufacturer, or any other interested party, gives CMS evidence about a selected drug and its therapeutic alternatives. The evidence corresponds to the factors in section 1194(e)(2) of the Social Security Act, and CMS draws on it when it adjusts the starting point of its initial offer for a maximum fair price (MFP) 1,2. For initial price applicability year (IPAY) 2029, the proposed CMS timeline sets the submission deadline at March 1, 2027, one month after the selected drug list is published 8. This guide covers what Section I collects, how CMS defines a therapeutic alternative, how the evidence is searched, extracted and written, and the statutory restriction on how comparative effectiveness evidence may be used. The program itself, the selected drugs and the manufacturer-specific data are covered in the Medicare Drug Price Negotiation manufacturer evidence guide.
1. What CMS ICR Section I Is
The Negotiation Data Elements ICR Form is form CMS-10849, approved under Office of Management and Budget (OMB) control number 0938-1452. The IPAY 2028 version was approved on January 9, 2026 and the approval runs to January 31, 2028 3. The form has two parts. Sections A through H are the Manufacturer-Specific Data Form, which collects the non-Federal average manufacturer price and the section 1194(e)(1) factors from the Primary Manufacturer. Sections I and J are the Evidence About Selected Drugs and Their Therapeutic Alternatives Form, which collects evidence under section 1194(e)(2) 5.
Data under section 1194(e)(1) must be submitted by the Primary Manufacturer. Section 1194(e)(2) does not name a source for the evidence it describes, so CMS accepts optional submissions from Primary Manufacturers and from the public, and also reviews the literature, runs its own analyses and consults clinical and subject matter experts 9.
2. Section I and the Section 1194(e)(2) Factors
Section 1194(e)(2) lists four kinds of evidence about alternative treatments that CMS must consider 1. Each Section I response serves one or more of them.
| Section 1194(e)(2) factor | Evidence that addresses it |
|---|---|
| The extent to which the drug represents a therapeutic advance over existing therapeutic alternatives, and the costs of those alternatives | Head-to-head trials, guideline positioning, clinical outcomes the alternatives have not shown |
| Food and Drug Administration (FDA) approved prescribing information for the drug and its therapeutic alternatives | Indications, approved populations, dosing, route, contraindications, boxed warnings, limitations of use |
| Comparative effectiveness of the drug and its therapeutic alternatives, including effects in specific populations | Randomized trials, indirect comparisons, network meta-analyses and real-world studies, with results in individuals with disabilities, the elderly, the terminally ill, children and other patient populations |
| The extent to which the drug and its therapeutic alternatives address unmet medical needs | Evidence on conditions that available therapy does not treat adequately, including nonresponse, intolerance and contraindications to the alternatives |
The section 1194(e)(1) factors are separate. They cover research and development costs and their recoupment, current unit costs of production and distribution, prior Federal financial support, patents, exclusivities and FDA applications and approvals, and market data with revenue and sales volume in the United States 1. Those data go in Sections A through H.
3. How CMS Uses Section I Evidence in the Initial Offer
Under the IPAY 2028 final guidance, CMS sets a starting point for the initial offer from the prices of the therapeutic alternatives, and for IPAY 2028 it added wholesale acquisition cost as one of the possible price sources (section 60.3.2) 2. CMS then adjusts that starting point on the basis of the section 1194(e)(2) factors, which include clinical benefit compared with the therapeutic alternatives (section 60.3.3). The analyses in sections 60.3.3.1 and 60.3.3.2 are conducted on the indications the selected drug shares with its therapeutic alternatives 2. Consideration of the manufacturer-specific data under section 1194(e)(1) is set out in section 60.3.4 2.
The identity of the therapeutic alternatives affects the price from which CMS starts. The comparative clinical evidence, organized by indication, informs the adjustment.
4. IPAY 2029: Form Status and Submission Timeline
The submission periods for IPAY 2028 have closed 6. CMS develops its Negotiation Program policies for 2029 and later years through notice-and-comment rulemaking 2. CMS issued the proposed rule (CMS-4215-P) on June 12, 2026, and published the revised Drug Price Negotiation ICR for IPAY 2029 with it. The comment period for both closed on August 17, 2026. CMS expects to issue the final rule and to send the final ICR to OMB in Fall 2026 6,7.
| Proposed IPAY 2029 milestone | Date |
|---|---|
| Selected drug list published | By February 1, 2027 |
| Negotiation Program Agreement signed | By February 28, 2027 |
| Manufacturer data and evidence about alternative treatments submitted | By March 1, 2027 |
| CMS initial offer | By June 1, 2027 |
| Negotiated MFP takes effect | January 1, 2029 |
The dates are from the CMS timeline issued with the proposed rule 8. One month separates publication of the selected drug list from the Section I deadline. The IPAY 2028 form is the most recent approved version, and question numbers and response limits in the IPAY 2029 form are fixed only when OMB approves it 3,6. EvySaif prepares Section I evidence files before selection for manufacturers whose products are likely candidates, with the systematic literature review and extraction completed ahead of the one-month window.
5. How Section I Is Organized and Submitted
In the IPAY 2028 form, Sections I and J run from Question 27 to Question 57 4. Section I questions are grouped by the type of respondent most likely to hold the information, such as patients and caregivers or clinicians, and any interested party may answer any question. Questions 28 through 33 are the patient or caregiver-focused questions 4. All questions are optional. Individual questions carry their own instructions on response length and content 4.
Primary Manufacturers submit through the CMS Health Plan Management System (HPMS), and the public uses a web form 4,5. A response can be saved and resumed before certification. After certification the submission cannot be changed, so quality control has to be complete before that step 4. CMS asks respondents to leave out personally identifiable information and protected health information 4.
6. How CMS Defines a Therapeutic Alternative
The CMS submission instructions define therapeutic alternatives as drugs that are used to treat the same condition or disease state as the selected drug 4. An indication is the condition or disease state that the selected drug treats, and it can include FDA-approved indications and certain off-label uses. An off-label use counts when it appears in evidence-based clinical practice guidelines and is a medically accepted use payable under Part B or covered under Part D 4. Unmet medical need exists when no other treatment options are available for the condition, or when existing treatments do not adequately address it 4.
Procedures, devices and non-drug interventions fall outside that definition. They belong in the description of the treatment pathway and in the unmet need discussion, and the list of therapeutic alternatives is a list of drugs.
7. Identifying Therapeutic Alternatives by Indication
Identification proceeds one indication at a time, because a drug that is an alternative in one indication may have no role in another. For each indication the file records the FDA-approved population, disease severity, line of therapy, route of administration, any biomarker requirement, and guideline-supported off-label uses that meet the CMS definition.
Candidate alternatives are then drawn from four source types: the prescribing information of drugs approved for the same indication, the drug class listings in formulary classification systems and compendia, the current clinical practice guidelines, and published drug class reviews. Each candidate is tested against the recorded population. A drug approved only after failure of two prior therapies is an alternative for that later-line population and is recorded as such. It is not listed against a first-line indication. A drug restricted to a biomarker-defined subgroup is recorded against that subgroup.
The output is a table with one row per indication and alternative pair, giving the approved population, the line of therapy, the guideline recommendation with its strength and date, and the reason for inclusion or exclusion. Excluded candidates stay in the table with the reason stated, because CMS may have identified them from the same sources. EvySaif builds this indication-by-alternative map from current labeling and guidelines and documents the inclusion rationale for each pair.
8. Literature Search and Screening for Section I Evidence
The search is built on four concepts combined for each indication: the selected drug, the indication, each therapeutic alternative, and the outcome of interest. Separate strings cover comparative effectiveness, safety, patient-reported outcomes, the specific populations named in section 1194(e)(2), and unmet need. PubMed/MEDLINE, Embase, the Cochrane Library and ClinicalTrials.gov are the core sources, supplemented by guideline bodies and FDA review documents. The strings, databases, dates and hit counts are recorded so the search can be rerun when the selected drug list is published.
Screening applies fixed criteria to every record.
| Criterion | Test applied |
|---|---|
| Population | The study population matches the indication and line of therapy under review |
| Intervention and comparator | The selected drug or a listed therapeutic alternative is evaluated, against a comparator used in practice |
| Outcomes | The study reports an outcome relevant to a section 1194(e)(2) factor |
| Design | The design is recorded: randomized trial, indirect comparison, observational study, systematic review |
| Setting | The care setting corresponds to where the drug is used |
| Currency | Labeling, guidelines and standard of care have not changed in a way that makes the study obsolete |
A study that names an alternative in its background section and reports no data on it fails the intervention criterion. Reasons for exclusion at full-text review are logged per study. EvySaif runs this search and screening as a documented systematic literature review with a reproducible protocol.
9. The Alternative-Treatment Evidence Table
Each included study is extracted once into a structured table, and every Section I response is written from that table.
| Field | Content |
|---|---|
| Therapy and class | Generic name, brand name, pharmacological class |
| Indication and population | Condition, line of therapy, key inclusion criteria |
| Design and comparator | Study type, comparator, sample size, follow-up |
| Efficacy outcomes | Endpoint, timepoint, effect estimate, confidence interval, P value |
| Safety outcomes | Serious adverse events, discontinuations, events of special interest |
| Patient-reported outcomes | Instrument, timepoint, result |
| Specific populations | Results in patients aged 65 years and older, patients with disabilities, other subgroups reported |
| Guideline position | Recommendation, strength, guideline year |
| Limitations | Design and applicability limitations stated by the authors or evident from the methods |
| Source location | Full citation with the page, table or figure that carries each extracted number |
The source location field makes every number in a response traceable to a page of a publication. Numbers are extracted as the primary source states them, with the same population, timepoint and denominator. EvySaif prepares these extraction tables and the longer study-level evidence summaries that sit behind a Section I response.
10. Writing a Section I Response
A response answers the question asked, within its limit, in this order: the therapy and its place in treatment, the population, the evidence, the result, and the limitation that affects interpretation. A single evidence sentence carries the design, the population, the comparator, the endpoint with its timepoint, the effect estimate with its confidence interval, and the citation.
Study findings are written in the past tense. "Superior" is used when a trial tested superiority and met it, and a noninferiority result is reported as noninferiority with its margin. A difference seen across separate trials is reported as an indirect observation with the differences in populations and endpoints stated. When no study has examined a question, the response says that no study was identified. It does not treat the absence of data as evidence of no difference. Manufacturer interpretation is placed after the results and is worded as interpretation.
The same fact can be relevant to several questions. It is stated in full once, where it fits best, and the other responses carry the conclusion with the citation. EvySaif writes Section I responses and supporting summaries in this register as part of its medical writing and health economics and outcomes research (HEOR) work.
11. Comparative Effectiveness, Indirect Comparisons and Network Meta-Analysis
Head-to-head randomized trials are the most direct evidence for the comparative effectiveness factor. Where they do not exist, an anchored indirect comparison or a network meta-analysis can estimate relative effects through a common comparator, provided the trials are similar in population, endpoint definition and follow-up. The response reports the method, the network or anchor, the effect estimate with its interval, and the heterogeneity or inconsistency findings. Unanchored comparisons of single arms are reported with their assumptions stated. A published network meta-analysis can be cited when its network reflects current treatment, and a new analysis is justified when the published networks omit a listed alternative. EvySaif conducts indirect comparisons and meta-analyses for this purpose.
12. Real-World Evidence and Medicare-Relevant Populations
Section 1194(e)(2) directs CMS to consider effects in specific populations, including the elderly and individuals with disabilities 1. Where the pivotal trials enrolled few patients aged 65 years and older, observational studies in claims data, registries and electronic health records supply the evidence for this factor. Each real-world study is reported with its data source, study period, cohort definition, comparator, method of confounding control and the share of patients in the Medicare-relevant age group. Treatment patterns, persistence, hospitalization and other resource use are reported as observed outcomes with their denominators. EvySaif designs and reports real-world evidence studies and extracts published ones for Section I files.
13. Cost-Effectiveness Evidence, QALYs and Section 1194(e)(2)
Section 1194(e)(2) bars CMS from using evidence from comparative clinical effectiveness research in a manner that treats extending the life of an individual who is elderly, disabled or terminally ill as of lower value than extending the life of an individual who is younger, nondisabled or not terminally ill 1. The quality-adjusted life year (QALY) weights each year of life by a health-state utility, so a year gained by a person with a chronic disability counts for less than a year gained in full health. Evidence built on that weighting falls within the concern of the clause.
Economic studies therefore enter a Section I file through their components. Life-years gained, clinical events avoided, hospital days and other resource use are extracted and reported as outcomes in their own right. The cost per QALY ratio is left out of the response. The extraction table records whether a study used QALYs so the point can be checked at quality control. Economic models built for health technology assessment agencies, described in the EvySaif HTA submissions service, need this adaptation before any part of them is used for CMS.
14. Unmet Medical Need and Specific Populations
The unmet need response follows from the CMS definition: either no other treatment exists, or existing treatments do not adequately address the condition 4. The evidence is specific to the alternatives already listed. It covers response and remission rates on those alternatives, discontinuation for intolerance, contraindications and drug interactions common in older patients, monitoring or administration burdens, and subgroups in which the alternatives have not been studied. Each statement names the alternative, the population and the source. General statements that an alternative is inferior are left out.
15. Quality Control Before Certification
Because a certified submission cannot be edited 4, the final review is done against a fixed list.
- Every number in every response matches the extraction table and the source page, including population, timepoint and denominator.
- Every claim carries a citation, and every citation resolves to the correct publication.
- Each response is within its limit and answers the question as worded in the approved form.
- The list of therapeutic alternatives is identical across all responses and matches the indication map.
- Labeling and guideline citations are the current versions on the submission date.
- No response reports a cost per QALY ratio.
- No patient-identifiable information appears anywhere in the submission.
16. CMS ICR Section I Evidence Support From EvySaif
EvySaif supports United States market access and HEOR teams, and the agencies that work for them, with the evidence and writing tasks behind a Section I submission:
- Therapeutic alternative mapping by indication from current labeling, compendia and guidelines
- Protocol-driven literature search, screening and extraction
- Study-level evidence summaries and extraction tables with page-level source anchors
- Indirect treatment comparisons and network meta-analyses
- Extraction and reporting of real-world and Medicare-population evidence
- Question-by-question Section I drafting, reference verification and pre-certification quality control
The same evidence base can be reused for payer dossiers in the AMCP Format. Project inquiries can be sent through the contact page.
17. Frequently Asked Questions
Sections A through H are required from the Primary Manufacturer. Section I is optional for every respondent, including the Primary Manufacturer 4,9. CMS considers the section 1194(e)(2) factors in every negotiation and builds its evidence from its own literature review, internal analyses and expert consultation as well as from submissions 9.
Anyone, including individuals and organizations. CMS groups the questions by likely respondent type, and any party may answer any question 4.
Section 1194(e)(2) names the evidence topics and sets no search method 1. A documented, reproducible search is the practical way to show that the evidence presented was selected by fixed criteria and to update it quickly after selection.
The statute restricts the use of comparative effectiveness evidence that values life extension differently by age, disability or terminal illness 1. Clinical and resource-use outcomes from economic studies are reported on their own, and cost per QALY ratios are left out.
The work covers mapping therapeutic alternatives by indication, running and documenting the literature search, extracting studies into evidence tables, conducting indirect comparisons where needed, drafting the question-by-question responses within their limits, and checking every figure against its source before certification.
References
- Social Security Act section 1194(e), 42 USC 1320f-3(e). Factors for negotiation of the maximum fair price.
- Centers for Medicare & Medicaid Services. Medicare Drug Price Negotiation Program: Final Guidance, Implementation of Sections 1191 to 1198 of the Social Security Act for Initial Price Applicability Year 2028 and Manufacturer Effectuation of the Maximum Fair Price in 2026, 2027, and 2028. September 30, 2025; corrected December 16, 2025. https://www.cms.gov/files/document/ipay-2028-final-guidance.pdf
- Office of Management and Budget. ICR reference 202511-0938-003: Drug Price Negotiation for Initial Price Applicability Year 2028 (CMS-10849), OMB control number 0938-1452. Approved January 9, 2026. https://www.reginfo.gov/public/do/PRAViewICR?ref_nbr=202511-0938-003
- Centers for Medicare & Medicaid Services. How to Submit the Public Submission Form for Reporting Evidence about Selected Drugs and Their Therapeutic Alternatives (IPAY 2028). https://www.cms.gov/files/document/how-submit-public-submission-form-ipay-2028.pdf
- Centers for Medicare & Medicaid Services. Instructions for requesting drug manufacturer access to the CMS Health Plan Management System (CMS HPMS). https://www.cms.gov/files/document/instructions-requesting-drug-manufacturer-access-cms-health-plan-management-system-cms-hpms-medicare.pdf
- Centers for Medicare & Medicaid Services. Medicare Drug Price Negotiation Program: Regulations, Guidance, and Policy Documents. Page last modified September 4, 2026. https://www.cms.gov/initiatives/medicare-prescription-drug-affordability/overview/medicare-drug-price-negotiation-program/regulations-guidance-policy-documents
- Centers for Medicare & Medicaid Services. Medicare Drug Price Negotiation Program and Medicare Prescription Drug Benefit Program; Proposed Rule (CMS-4215-P). Federal Register. June 16, 2026. https://www.federalregister.gov/documents/2026/06/16/2026-12059/medicare-drug-price-negotiation-program-and-medicare-prescription-drug-benefit-program
- Centers for Medicare & Medicaid Services. Initial Price Applicability Year 2029 Negotiation Program Timeline. June 12, 2026. https://www.cms.gov/files/document/mdpnp-nprm-milestones.pdf
- Centers for Medicare & Medicaid Services. Agency Information Collection Activities; Negotiation Data Elements under Sections 11001 and 11002 of the Inflation Reduction Act. Federal Register. July 3, 2023. https://www.govinfo.gov/content/pkg/FR-2023-07-03/pdf/2023-14097.pdf
EvySaif Research Solutions is a clinician-led medical writing, regulatory affairs, HEOR and drug clinical development consultancy serving pharmaceutical, biotechnology and medical device companies across India, the Middle East and Europe.
Last reviewed: September 2026. This article is provided for general information and does not constitute legal, regulatory or pricing advice. The dates for initial price applicability year 2029 are those proposed by CMS in June 2026 and are subject to the final rule.