HEALTH TECHNOLOGY ASSESSMENT GUIDELINES DRUG SUBMISSION GUIDELINES FOR RE-EVALUATION OF PRODUCTS, INDICATIONS, AND FORMULATIONS

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1 HEALTH TECHNOLOGY ASSESSMENT GUIDELINES DRUG SUBMISSION GUIDELINES FOR RE-EVALUATION OF PRODUCTS, INDICATIONS, AND FORMULATIONS National Pharmacy and Therapeutics Committee WellPointNextRx Updated September 2008

2 THE WELLPOINT OUTCOMES BASED FORMULARY SM REFERENCE DOCUMENTS WellPoint, Health Technology Assessment Guidelines: Drug Submission Guidelines for New Products, New Indications, and New Formulations (Updated September 2008). WellPoint, Health Technology Assessment Guidelines: Drug Submission Guidelines for Re- Evaluation of Products, Indications, and Formulations (Updated September 2008). WellPoint, Health Technology Assessment Guidelines: Evidentiary and Analytical Standards in Health Technology Assessments (forthcoming). 2

3 TABLE OF CONTENTS 1. THE WELLPOINT OUTCOMES BASED FORMULARY SM 1.1 Guidelines in the WellPoint System 1.2 Evidentiary and Analytical Standards 1.3 Literature Searches 2. UPDATE OF PRODUCT DESCRIPTION AND INDICATION 2.1 Product Description 2.2 Product Utilization Review 2.3 Future Indications 3. REVIEW OF TARGET POPULATION, TREATMENT PATTERNS, AND OUTCOMES 3.1 Epidemiology of the Disease State 3.2 Treatment Patterns and Place of the Product in Therapy 3.3 Comparator Therapies 3.4 Treatment Outcomes 3.5 Pharmacovigilance 4. REVISED CLINICAL ASSESSMENT 4.1 Revised Claims for Treatment Effect 5. REVISED COST-OUTCOME ASSESSMENT AND PRODUCT CLAIMS 5.1 Revisiting Cost-Outcome Claims 5.2 Evaluating a Cost-Effectiveness Claim 5.3 Compliance 5.4 Dosage, Titration, and Other Utilization Patterns 5.5 Reconciling Prior Cost-Outcomes Claims 5.6 Presenting Revised Cost-Effectiveness Claims 5.7 Spreadsheet Modeled Claims 6. REVISED BUDGET AND SYSTEM IMPACT CLAIMS 6.1 Establishing Budget Impact Claims 6.2 Evaluating Prior Budget Impact Claims 6.3 Revised Budget Impact Claims 6.4 Impact on Patient Population Outcomes 7. SUBMITTING FUTURE CLAIMS 7.1 Ongoing Reviews 7.2 Long-Term Responsibility of Manufacturers 3

4 INTRODUCTION WellPoint (WP) has developed separate companion guidelines to support (i) initial assessments of new products, new indication, and new formulations and (ii) re-evaluation of products as part of ongoing disease area and therapeutic class reviews. This document presents the evidentiary and analytical standards required by WP to support ongoing disease area and therapeutic class reviews. The standards required are the same as those established by WellPoint for new product submissions; the key point of difference is that in making subsequent submissions, manufacturers are asked to provide comprehensive and high quality data to demonstrate that prior claims for clinical benefit, quality of life, workplace productivity, cost-effectiveness, and budget impact for the target population have been substantiated. The evidentiary and analytical standards proposed here for formulary re-submissions to WP may become mandatory in the future. The Drug Submission Guidelines for Re-Evaluation of Products, Indications, and Formulations, is intended for manufacturers who are responding to a request for data when a product is being reevaluated by the CRC and VAC as part of ongoing disease area and therapeutic class review. However, if a dossier has not been previously submitted using the guidelines for new evaluations (Drug Submission Guidelines for New Products, New Indications, or New Formulation), then manufacturers should ensure that they respond to the evidentiary and analytical standards detailed in both companion guidelines. Where a submission is being prepared to meet these updated guidelines, manufacturers should note the emphasis being placed by WellPoint on claims that are presented in terms of (i) the total cost impact of the product on the WellPoint budget (in per member per year terms); (ii) the quality of life claims associated with the product; (iii) the potential workplace productivity impact of the product; and (iv) the cost-effectiveness claims associated with the product. This version of the WP guidelines supersedes the document issued in September The revised guideline has been extensively re-written to emphasize the evidentiary and analytical standards required for product re-submissions. The principal focus of re-submissions is on evidence to support prior claims for product impact as the basis for maintaining a product s formulary position. Manufacturers are asked to report on studies undertaken to monitor and validate product claims and to detail reasons for potential discrepancies between claims for treatment effect and their actual impact. This follows from the commitment of WP to the role of the WellPoint Outcomes Based Formulary SM 4

5 1. THE WELLPOINT OUTCOMES BASED FORMULARY SM 1.1 Guidelines in the WellPoint System The commitment of WP to the principles of the WellPoint Outcomes Based Formulary SM underpins the evidentiary and analytical requirements set down in the WP formulary submission guidelines. These standards apply equally to submissions made to support new products, indications, and formulations as well as to submissions supporting product re-evaluations. The principal difference in the two guidelines is that for product re-submission, manufacturers are asked to justify prior claims made for product performance in the WP treating population. WP is committed to optimizing patient outcomes through the application of the principles of the WellPoint Outcomes Based Formulary SM. In the case of new products, new indications, and new formulations for existing products, this is achieved by asking manufacturers and others making submissions for formulary evaluation to meet certain evidentiary and analytical standards in their submission. As well, manufacturers should be aware that product claims will be subject to an ongoing process of reviews over the balance of the life cycle of the product. The standards recommended for submissions to ongoing product reviews are the subject of these guidelines. The role of ongoing product reviews should be seen as a key element in WP s commitment to the process of continuing health technology assessment. The principal objective in this process is to ensure that the most appropriate and clinically beneficial health care technologies and interventions remain available to plan members, and that these technologies continue to be delivered and utilized in the most efficient, safe, and effective way possible. 1.2 Evidentiary and Analytical Standards Evidence presented in support of an application to WP for formulary re-evaluation must meet accepted standards in both evidence-based medicine and health technology assessment. Meeting the evidentiary and analytical standards proposed in these guidelines represent a key input to the commitment of WP to evidence-based medicine. This commitment is seen in the recommendation that the clinical assessment and product claims presentation should meet standards for high quality systematic reviews and meta-analyses. Claims for cost-effectiveness should be firmly grounded in the clinical data. Where a modeled case for cost-effectiveness is presented it should meet accepted standards in health technology assessment, be free from any bias in incorporating estimates of relative treatment effectiveness, and be completely transparent. Models should not only be plausible and replicable, but they should be appropriate to the WP population. These requirements apply equally to initial product submissions as well as submissions for product re-evaluation. Indeed, during the re-evaluation process, the key question will examine how well modeled cost-outcomes claims have stood up to empirical evaluation. These results may have implications for future claims in support of the next review cycle. 5

6 1.3 Literature Searches By the time a product is being reevaluated by WP, it will have been on formulary for up to 3 years. Within this time frame, a body of published literature should have been generated. The manufacturer should identify this body of published literature and add them to the materials used to support an initial formulary submission. These more recent studies should be identified, including additional studies for comparator products. The same standards for assessment of the initial submission material apply to newly-submitted published as well as unpublished studies. It is important that continuity is maintained in the successive submissions to WP to support a product s formulary position over its patent life and into the generic phase. Therefore, manufacturers should detail searches undertaken in prior submissions and show how the search has been updated to capture more recent material. As before, it is recommended that all studies and systematic reviews (both published and unpublished) that have been excluded be identified and that a brief summary of their limitations be included in the re-submission. WP recognizes that when reporting on prior claims made to WP for the product, there may be reasons why the results of such assessments are not available in the peer reviewed literature. In this case, manufacturers should provide all unpublished reports relating to these claims. 6

7 2. UPDATE OF PRODUCT DESCRIPTION AND INDICATION When responding to a request for a submission to support the re-evaluation of a product, manufacturers should state whether or not there has been any change in product description and indication since the product was last reviewed. If there has been no change, the manufacturer should proceed to the next stage of the report. 2.1 Product Description A detailed product description is a key element in a formulary submission evaluation. If there have been any changes, these should be detailed against the initial product description provided by the manufacturer to WP. Provide a description of any changes in the product profile (including details of any changes in product indication and formulation) in terms of the following elements: a. A copy of the official product labeling / literature b. Generic name, brand name, and therapeutic class of product c. List of all dosage forms, including strengths and package sizes d. FDA approved indications e. Other studied indications or uses for non-approved indications Including a breakdown by percentage of use for each labeled indication as well as key off-label uses f. Pharmacology g. Pharmacokinetics h. Contraindications i. Warnings / Precautions j. Adverse events / reactions k. Interactions (drug / drug, drug / food, drug / disease), with suggestions on how to avoid them l. Dosing and administration m. Length of course of treatment, and frequency of repeat courses expected (due to therapy failure) n. Average Wholesale Price (AWP) o. Confirmation of ability to supply anticipated demand for product at proposed price p. Comparison with the pharmacokinetic / pharmacologic profile of comparator products on the WP formulary (tabular form) q. A summary of current patents on the product, their expiration dates (including applicable pediatric extensions that are approved or have been applied for), and identification of which patent is likely to be the key patent barring generic competition Note that in reporting average wholesale price, manufacturers should detail all price increases that have occurred since the product was first listed in the WP formulary. 2.2 Product Utilization Review Manufacturers are asked to provide details of utilization of the product (including offlabel use) since the initial or last submission made to WP. 7

8 WP asks manufacturers to monitor and validate initial/prior claims made for a product once it has been listed on the WP formulary. An important part of this process is to track utilization of the product against initial claims made for initial product uptake and the characteristics of patients who have used or are currently using the product. Specifically, WP requires information on: Total unit sales in the US for each year since product launch Current formulary position(s) of the product in US managed care Estimate of the extent to which patients have moved from other products to the manufacturer s product in each year since product launch, listed by product Characteristics of the patients who have moved to the product or who are currently receiving the product Estimated medication possession (compliance) with the product in US managed care Estimated off-label utilization of the product in US managed care Estimate of medical cost offsets (or total cost of care) over a certain duration of time associated with the product WP is particularly interested in compliance behavior. Manufacturers are expected to track compliance with the product as part of an ongoing process of monitoring and validation. Where possible, manufacturers should provide estimates of product retention (or survival) and patterns of medication possession. If manufacturers have undertaken assessments of compliance behavior, including evaluations of factors associated with poor compliance, these should be reported as part of this submission. 2.3 Future Indications In assessing the potential system-wide impact of the product, manufacturers should provide details of planned or anticipated future new indications and/or formulations of the product. In evaluating the future impact of a product, manufacturers should provide details of potential new indications and/or new formulations that are being considered as part of the product development process. Specifically, manufacturers should provide information on the following: (i) (ii) (iii) New indication(s) anticipated/sought; New formulation(s) anticipated/sought; The anticipated date of new indication/formulation approval by the FDA. Where a new indication is being sought, manufacturers should provide an estimate of the anticipated market share for the product and the number of patients likely to move to the product in a population representative of the WP system. For new formulations, manufacturers should provide evidence of unmet need and rationale for new formulations. 8

9 3. REVIEW OF TARGET POPULATION, TREATMENT PATTERNS, AND OUTCOMES A clinical, cost-effectiveness, and budget impact assessment of a product should rely on an appreciation of the underlying epidemiology of the disease state, an estimate of the number at risk within the WP system, treatment patterns, and the place in therapy of the product. Where a previous submission has been made detailing the epidemiology of the disease state and the product s place in therapy, it is important to revisit prior claims and confirm their continued relevance. 3.1 Epidemiology of the Disease State Manufacturers are asked to update information provided in their previous submission regarding the epidemiology and treatment patterns of the indicated disease state. The following data elements formed part of the initial product submission: (i) Definition/classification of the disease state/therapeutic area; (ii) Characteristics of the target patient population; (iii) Characteristics of clinically distinct or prospective sub-populations within the target patient population; (iv) Criteria for identifying sub-populations; (v) Annual prevalence/incidence; (vi) Annual treating prevalence/incidence; (vii) Trends in prevalence/incidence; (viii) Trends in treating prevalence/incidence; (ix) Risk factors for the disease. Manufacturers are asked to update this profile, indicating where substantive changes have occurred that are relevant to the target WP treating population. New data available (e.g., administrative claims data) to support revised estimates of treating incidence and prevalence should be detailed. 3.2 Treatment Patterns and Place of Product in Therapy The introduction of a new product in a disease or therapeutic area can have a significant impact on treatment patterns. Manufacturers should detail the changes that have occurred in treatment patterns in the indicated disease area since their previous submission, pointing to the contribution of their product and competing products. To help WP better understand the real-world utilization of the product in clinical settings, WP asks manufacturers to provide information about dosage, dose titration, and other treatment patterns observed in clinical practice. This knowledge about utilization would help WP better determined the product s most appropriate place in therapy. 9

10 Monitoring and validating the impact of a new product on treatment patterns in a target disease or therapeutic area is important. WP is concerned about how prior claims for the expected place of the product in therapy compare to current treatment patterns. Where there are substantial discrepancies between prior claims and subsequent experience, these should be detailed and accounted for by the manufacturer (e.g., off-label utilization). The manufacturer should also detail the extent to which current treatment patterns for the product may have modified prior claims for clinical benefit, cost-effectiveness, and budget impact (see Sections 5 and 6 below). Specifically, manufacturers are asked to detail (for the 12 months prior to the current submission): commonly used dosages of medication in clinical practice dosage titration (the proportion of patients titrated to goal) medication compliance treatment persistence (how long the patient was on therapy over one year) switching/augmenting rates discontinuation rates (hazard curve for rates of discontinuation) a statement of the extent to which the anticipated place of the product in therapy conforms to the observed place in therapy a projection of the product s place in therapy over the next three years 3.3 Comparator Therapies Comparator therapies or procedures are those that may be able to substitute for the product in clinical practice. WP is interested in the extent to which prior expectations of comparator products have been met and whether or not the current status of the product may be challenged by new products. In making their initial submission to WP, manufacturers were asked to detail those products or procedures which would be considered comparators and the extent to which substitution against comparators was expected to occur in the first 3 years following product entry. In making a resubmission manufacturers are asked for: a statement detailing the extent to which previous predictions regarding the role of comparator products and procedures and the extent of product substitution have been established in clinical practice a statement identifying potential new comparators (or further comparator substitution) and the extent to which the entry of new products in the disease area may affect current utilization patterns for their product (note the requirement for budget impact projections in Section 6 below) 3.4 Treatment Outcomes For WP, a key issue is the extent to which prior claims for a product s clinical, quality of life, productivity, cost-effectiveness, and budget impact on the target WP population have 10

11 been achieved in treatment practice. Manufacturers are asked to provide a summary statement of the outcomes achieved, detailing the studies that have been undertaken to support these claims WP is aware that there is a limited amount of high quality outcomes evidence that is relevant to the information needs of clinical and health system decision makers. Evidence from systematic reviews/meta-analyses points to the fact that all too often the evidence quality is questionable. As such, it is often difficult to provide definitive recommendations for care interventions and make decisions, from a reimbursement perspective, concerning the long term benefits and risks of competing products. Once a product has entered clinical practice, manufacturers have the opportunity to substantiate, through well-designed and high quality clinical effectiveness trials, the impact of their product in clinical practice within the WP or similar managed care system. It is assumed that manufacturers have proposed, as part of an initial or prior submission, studies appropriate to substantiating product claims. If the manufacturer has undertaken other impact assessment studies (e.g., Phase IV marketing support studies) these should also be reported, together with any other product assessment studies that have appeared in the clinical literature which may not have been supported by the manufacturer. Manufacturers are asked to provide a summary statement of: studies that were expected to be undertaken by the manufacturer at the time of product launch to evaluate the clinical, quality of life, and workplace productivity impact in the target WP population, together with claims for cost-effectiveness and budget impact current status of all studies, indicating expected completion date if not already reported studies detailing the extent to which predictions made about product impacts match observed outcomes 3.5 Pharmacovigilance WP is concerned with the ongoing safety profile of products introduced to its formulary. Manufacturers are expected to detail proposed pharmacovigilance processes and to report safety issues on a regular (and agreed-upon) basis. Manufacturers are asked to provide a concise summary of all pharmacovigilance activities undertaken to support their product. A detailed summary of all adverse reports should be provided to WP detailing, for all markets, the impact of the product since launch. Manufacturers should detail whether or not any changes are proposed to the pharmacovigilance program. 11

12 4. REVISED CLINICAL ASSESSMENT The purpose of the WP clinical assessment is to produce an unbiased estimate of the clinical efficacy, safety, and effectiveness of the product against comparator therapies. The term clinical effectiveness includes claims for patient reported outcomes, including quality of life. When a manufacturer responds to a request for a product re-evaluation, the principal purpose is to update clinical impact claims reported in a previous submission. The assessment should encompass both new clinical data as well as new clinical evidence for comparator products, formulations, or indications. In order to properly evaluate the updated clinical evidence for a product, it is important that WP has access to (i) comprehensive clinical assessments of the product (including new indications for an existing product and new formulations) and (ii) comprehensive clinical assessments of the comparator products or procedures for the indication sought, at the dosage and formulation approved by the FDA. Manufacturers should: Report the literature search procedures undertaken to identify clinical studies, Report the criteria applied for excluding studies which are not considered relevant to the assessment, Undertake a systematic review of the relevant studies, Prepare individual study summaries, Prepare a summary statement of clinical advantage, Undertake systematic reviews/meta-analyses of comparable studies, Identify potential clinical subgroups within the target population, Describe the generalizability of the outcomes reported, and Provide reprints of the literature used in the preparation of the clinical assessment. WP approaches the clinical assessment of products using the principles of evidence-based medicine. As such, only clinical evidence of high quality is considered when updating efficacy and effectiveness assessments. However, lower quality evidence may be considered during assessment of product adverse effects and harms; any such studies should also be included in the safety section of the submission. All reports, summaries, and systematic reviews/meta-analyses included in the submission are expected to follow these same principles. It is important for manufacturers to provide transparency in the process used for evaluating the literature to determine its quality. Studies with significant threats to validity should not be included in clinical reviews; however, these studies should be listed as excluded with the reason for exclusion. For systematic reviews/meta-analyses, studies with significant threats to validity should not be included unless the appropriate sensitivity testing proves that they do not adversely affect the analysis. In addition to summarizing individual clinical studies, systematic reviews/meta-analyses should be undertaken where appropriate. These analyses provide a key link to the treatment effect assumptions underpinning the modeling of cost-effectiveness and budget impact claims. Metaanalyses undertaken by manufacturers will be subject to the same quality assessment as published studies. Therefore, it is important for manufacturers to provide significant detail as to 12

13 their methodology, data analysis, the magnitude of the treatment effect, the precision of the treatment effect, and assessment of potential biases. Where new studies have been published, these may modify previous systematic review/ meta-analysis-based claims for treatment effect. 4.1 Revised Claims for Treatment Effect Claims for treatment effect are a cornerstone of comparative product assessments, costeffectiveness claims, and budget impact assessments. It is important that prior claims for comparative treatment effect, which for new products are principally trial-based, are subject to reassessment in a clinical practice environment. As part of their commitment to monitoring and validating treatment effect claims (clinical, quality of life, and workplace productivity), manufacturers are asked to propose and report studies that evaluate product impacts in a clinical practice environment. This process involves: (i) summarizing the results of all studies, for both the manufacturer s product and comparator products, undertaken since the previous submission in the required WP format; and (ii) evaluating and updating previous claims for comparative treatment effect. WP is particularly interested in active comparator, clinical effectiveness trials for the manufacturer s product; especially trials which involve medical cost impact, quality of life endpoints, and workplace productivity related claims. Manufacturers should be clear about whether or not they believe more recent treatment effect claims significantly modify prior claims for comparative product performance. If necessary, manufacturers should reassess and rework previous systematic reviews/meta-analyses for their re-submission. Where a new product or formulation has entered the market place in competition with the manufacturer s product, a complete clinical evaluation of the new comparator product or formulation is required as part of the updated assessment of the manufacturer s product claims for comparative treatment effect and statement of clinical advantage. 13

14 5. REVISED COST-OUTCOME ASSESSMENT AND PRODUCT CLAIMS 5.1 Revisiting Cost-Outcome Claims WP expects manufacturers to justify prior claims made for product cost-effectiveness. This is achieved by monitoring and validating prior claims as well as evaluating the basis for prior modeled claims. The WP guidelines to support initial product submissions emphasize that the only costeffectiveness claims acceptable to WP are those that are amenable to empirical verification. Modeled claims for cost-effectiveness, in particular those for chronic conditions that take a longterm or lifetime perspective, are unlikely to be useful for WP formulary decisions. WP is interested in claims for cost-effectiveness that can be evaluated within a 3 year time horizon. Manufacturers are expected to present claims in this form and, as part of the previous submission process, propose how these claims are to be monitored and verified. Each element of the claim for cost-effectiveness should be matched to a proposed study design. The results of these assessments are to be presented as part of a product re-submission. Manufacturers should also note that even when a first product submission is being made to WP, if this product has been available in the US market, then assessments validating costeffectiveness claims should be presented. These claims may be in the form of modeled claims that have appeared in the peer reviewed literature; if so, WP would expect a re-evaluation of those claims to be presented for the WP target population as part of the resubmission. Manufacturers are asked to update any prior cost-effectiveness literature reviews, to include both peer reviewed cost-effectiveness assessments as well as health technology assessments undertaken by national agencies. Study summaries should be provided in the WP required format, including both updates for prior comparator therapies as well as new, potential comparator therapies which have received FDA marketing approval. 5.2 Evaluating a Cost-Effectiveness Claim It is the responsibility of the manufacturer to report the results of studies undertaken to evaluate prior claims for cost-effectiveness in the WP treating environment. WP recognizes that following marketing approval for a new product, modeled claims for costeffectiveness are the principal source of cost-effectiveness information. However, such claims (including trial-based treatment effect claims) and the decisions on formulary positioning based on these claims are only considered provisional. Validating and monitoring clinical, costeffectiveness, and budget impact claims provides, in the context of WP s commitment to an outcomes based formulary, a considerably more robust evidentiary framework for continued support and formulary listing of the manufacturer s product. Manufacturers are expected to provide a detailed evaluation of each prior claim made for costeffectiveness. While this requirement is not mandatory, a detailed evaluation (which may be undertaken by independent third parties at the manufacturer s discretion) is a critical input to 14

15 decisions regarding continued formulary positioning. The framework for evaluating claims is entirely at the discretion of the manufacturer (e.g., choice of prospective, active comparator study design). However, the framework used should be consistent with the proposals for claims assessment made in the initial or previous product submission. In general, manufacturers should use administrative claims databases to examine the total cost of care and re-examine their costeffectiveness estimates. 5.3 Compliance Modeled claims for cost-effectiveness should incorporate compliance behavior into the outcomes assessment. Modeled claims for product cost-effectiveness seldom take into account the impact of compliance behavior on resource allocation and treatment costs. In assessing the extent to which initial claims for cost-effectiveness have been substantiated, manufacturers are asked to describe the impact of compliance behavior on outcomes achieved and the extent to which compliance patterns are expected to impact revised modeled claims for cost-effectiveness. 5.4 Dosage, Titration, and Other Utilization Patterns Modeled claims for cost-effectiveness should incorporate information regarding the observed dosage, dose titration, and utilization patterns into the outcomes assessment. In clinical practice, the treatment dosage, titration schedule, and utilization patterns may differ from those expected based on the results of clinical studies. The revised claim for product costeffectiveness should account for the impact of these observed differences, if any. 5.5 Reconciling Prior Cost-Effectiveness Claims WP asks manufacturers to provide a comprehensive reconciliation of modeled cost-effectiveness claims against post-market entry assessments of product impact. Manufacturers are asked to present a detailed assessment of any discrepancies between prior modeled (or trial-based claims) and observations concerning the cost-effectiveness of the product in a WP treating environment (or similar managed care environment), from a disease intervention or incidence perspective. Monitoring and validation should describe and account for any discrepancies in terms of: cost-effectiveness decision model structure and timeframe assumptions regarding model and parameter uncertainty predictions regarding resource utilization profiles for the new product predictions regarding unit pricing of resources predictions regarding place of the product in therapy choice of outcome measure 15

16 assumptions regarding compliance behavior assumptions concerning utilization patterns predictions regarding outcomes (clinical and patient-reported) 5.6 Presenting Revised Cost-Effectiveness Claims Manufacturers, as part of their re-submission, should present revised modeled cost-effectiveness claims as the basis for subsequent assessments of product impact. Manufacturers are asked, not only to account for any discrepancies between prior costeffectiveness claims and the impact of their product within the WP treating environment, but to also provide revised claims for comparative product cost-effectiveness for the next review period of 3 years. Revised claims should take into account the potential entry of new products since the previous submission. These claims are expected to be monitored and verified within the WP treating environment as part of future responses to further product reassessment. 5.7 Spreadsheet Modeled Claims Manufacturers should submit a revised and updated spreadsheet modeling the claim for product cost-effectiveness. Once a re-assessment of the initial modeled claim for cost-effectiveness has been completed, manufacturers are asked to submit a revised and updated spreadsheet-based model of the costeffectiveness claim. This will serve as the basis for re-assessment of the product claims and further review. 16

17 6. REVISED BUDGET AND SYSTEM IMPACT CLAIMS As well as providing a revised claim for cost-effectiveness, manufacturers are also asked to (i) review prior claims made for budget impact and (ii) provide an updated claim for budget impact for the next 3 years. In addition, manufacturers are asked to report the impact of the product on the WP treating population from an annual prevalence perspective. Manufacturers are advised that WP is not in the position to support them in assessing budget impact claims. Claims for budget impact can be based upon data from any health care system as long as the results can be generalized to the WP target population. 6.1 Establishing Budget Impact Claims Manufacturers should undertake a detailed evaluation of prior claims for the budget impact of introducing their product onto the WP formulary. This evaluation should assess not only the overall budget impact in total costs and per member per year (PMPY) terms, but should also consider the assumptions that were built into the prior budget forecasts Manufacturers were asked, in making an initial submission for their product, to provide estimates of the anticipated budget impact in each of the first 3 years following formulary listing. As detailed in the WP guideline, the first step in evaluating the system impact of introducing a new product is to give estimates of the characteristics and number of patients who are expected to begin the new product in the disease and/or therapy area. Manufacturers were asked to detail, for each of the three years following formulary listing by WP: The characteristics of patients who are expected to transition to the new product from the comparator product(s); and The number (or proportion) of patients who are expected to initiate therapy Manufacturers should indicate how these new patients are to be identified from administrative claims data. Manufacturers should provide identifiers (e.g., ICD-9 codes; CPT codes) that will allow WP to monitor patient adherence or non-adherence patterns and validate the claims made by the manufacturer. Manufacturers were asked to detail the net impact of introducing the new product on resource utilization within the disease or therapeutic area, the impact on the associated unit prices for the medical and pharmacy resource inputs, and the impact of projected patterns of product uptake on medical, pharmacy, and total direct costs of treatment. These forecasts were to be presented for each of the first three years following formulary listing, with summary estimates of total cost impact presented in per member per year (PMPY) terms. Manufacturers were also asked to present budget impact forecasts as an electronic spreadsheet. 6.2 Evaluating Prior Budget Impact Claims Manufacturers are asked to utilize administrative claims data (not necessarily from the WP 17

18 system) as the basis for evaluating prior claims for budget impact. Assessments of prior estimates of budget impact for the WP system should be based upon administrative claims data. These data do not have to be from the WP system, but may be from other systems with comparable characteristics. The evaluation should identify, for each of the three years following formulary listing, the following data elements: product uptake in prescription units (monthly equivalent scripts) estimated displacement of comparator prescription units (monthly equivalent scripts) number of patients taking up the new product estimated number of patients moving from comparator products net resource utilization impact of formulary listing impact on pharmacy, medical, and total costs of formulary listing Estimates of the cost impact of formulary listing should be expressed in net terms for the disease or therapeutic area as well as for the product and its individual comparators. This will allow WP to assess any net gains/losses in resource utilization and costs by product within the disease area. As well as producing overall estimates of budget impact for the WP system, these estimates should also be presented as per member per year (PMPY) costs. 6.3 Revised Budget Impact Claims In contributing to WP s ongoing commitment to re-evaluating the impact of competing therapies within disease areas, manufacturers are asked to provide revised budget impact claims for the next 3 years. Manufacturers are asked to provide modeled estimates of the anticipated budget impact claims for the product for each of the next 3 years following product resubmission. These should be consistent with revised claims for patient population outcomes (see 6.4 below). Modeled claims for budget impact should capture medical, pharmacy, and total cost impacts as well as projected estimates of these in PMPY terms. 6.4 Impact on Patient Population Outcomes The principal reason for adding a product to formulary is acceptance of the claim by a manufacturer that the product yields additional clinical benefits and that, for the cost incurred, this is judged to be of significant value by WP. Therefore, from the WellPoint Outcomes Based Formulary SM perspective, it is important that clinical and quality of life claims are monitored and validated for the population of patients who are introduced to a new therapy. In making a cost-effectiveness and value case for a new product, new indication, or new formulation, manufacturers should recognize the importance of ensuring that both clinical and 18

19 quality of life related claims for the target WellPoint population are capable of being monitored and verified from a health system or patient population perspective. Given WP s commitment to the WellPoint Outcomes Based Formulary SM, it is important to track the treatment experience and the distribution of outcomes for the population of patients who are introduced to the new therapy. Manufacturers are asked to report the impact of introducing their product on the outcomes achieved for the target WP population. The focus should be on the distribution of outcomes achieved for those patients who have moved to the product, including estimates of the proportion of patients treated who have achieved target outcomes in the disease or therapy area, as appropriate. As in the case of cost-effectiveness claims, manufacturers are asked to account for any discrepancies between prior claims for treatment impact and outcomes actually achieved. Manufacturers are asked to provide revised estimates of the population outcome impact of their product for the 3 years following product re-submission. 19

20 7. SUBMITTING FUTURE CLAIMS Manufacturers making a re-submission are expected to provide details describing how they propose to further monitor and validate their product in the WP system. Tracking product impact is an integral part of WP s commitment to an outcomes based formulary, a commitment to effectiveness and safety considerations as well as issues of continued cost-effectiveness and budget impact that extends over the lifetime of the product. 7.1 Ongoing Reviews Manufacturers should anticipate that, over the lifetime of their product, WP will request a number of re-submissions to support reassessment of their product s place on the WP national formulary. Re-submissions would be expected to include both reassessments of prior claims for the place of the product in therapy as well as revised claims for comparative treatment effectiveness, safety, cost-effectiveness, and budget impact which, in turn, will be reassessed as part of future submissions to WP. Monitoring and validation of claims are central to this process. At each re-submission stage WP may, if considered appropriate, meet with the manufacturer to both assess the merits of previous claims for product impact as well as to review proposals for continuing re-assessments. The focus of reviews will be on: Claims that should be monitored and validated The methodology for monitoring and criteria for validation The prospective role of the manufacturer or a third party in monitoring and validation This requirement for monitoring and validation applies with equal force to claims based on patient sub-groups. 7.2 Long-Term Responsibility of Manufacturers WP is committed to the establishment of an outcomes based formulary in all of its business areas. Approval and placement of a product on the WP national formulary is evidence-based. As such it should be seen as provisional. As claims for a product are monitored and verified, and as the clinical and competitive landscape within a disease or therapeutic area changes over a product s patent life, the comparative benefits conferred by a product would be expected to change as well. It is the responsibility of manufacturers within a disease area to respond to WP s information needs and thereby ensure that the most effective treatments are delivered to the WP population. 20