AMCP Format for Formulary Submission Version 4.0: Call for Comments. January 2016.
Attn: Dr. Susan Oh, PharmD, Assistant Director of Pharmacy Affairs, Academy of Managed Care Pharmacy
The National Pharmaceutical Council (NPC) commends the Academy of Managed Care Pharmacy (AMCP) and the Format Executive Committee on the revised AMCP Format for Formulary Submissions. As a health policy research organization dedicated to the advancement of good evidence and science, we are encouraged to see the Format’s revision supports the use of high-quality evidence in decision-making, encompasses a holistic view of the value of innovative treatments, allows for communication between stakeholders, and ultimately seeks to improve patient health. These revisions ensure that AMCP Format-based dossiers meet the evolving environment for high-quality and robust evidence to inform the role and value of innovative treatments in health care. At a time when new and novel treatments are curing diseases, multi-modal treatments combining diagnostics, devices, and biopharmaceuticals are being developed, biosimilars are emerging, new information sources and study designs are available, and reimbursement is based on quality and value rather than volume, clear communication channels between innovators and decision-makers are needed.
We applaud the Academy’s guidance for the following revisions:
- The Format’s recognition of the need for timely, quality, and relevant clinical and economic information from manufacturers to health care decision-makers. New and innovative medicines bring value to patients, our health system, and health care decision-makers. By better targeting diseases, developing personalized and targeted therapies, and improving care pathways, together, we can reduce patient side effects and adverse events, avoid costly inpatient expenditures, keep patients out of the hospital, and improve patient health.
- These efforts require consideration of the best available evidence to inform decision-making, regardless of the study design. The Format recognizes the importance of appropriate study design, high-quality analytic techniques, and trustworthy data sources. The inclusion of tools to increase the clarity, consistency, and transparency of evidence evaluation provides a guide for biopharmaceutical manufacturers on the evidence standards health care decision-makers expect.
- Critical to health care delivery is identifying which treatments will work for which patients and understanding when patient differences matter. The increased recognition of heterogeneity of treatment effects and the need to communicate and consider this information ensures that patients have appropriate access to treatments based upon their characteristics.
- With the proliferation of initiatives to develop value frameworks, we appreciate the recognition that budget impact analyses do not establish the overall value of health care treatments. Budget impact analyses offer important information, but they do not include the full impact of the technology on clinical and patient impacts.
- As the health care system transitions from volume to value, now more than ever, credible and valid evidence is needed on the clinical, economic, and humanistic outcomes and quality measures. Central to this is the continued Format recognition of the current barriers that exist in the exchange of information between health care decision-makers and biopharmaceutical manufacturers. Continued discussions to reduce the barriers for credible and meaningful communication are needed. However, the unsolicited request mechanism offered by the Format whereby health care decision-makers request information from the manufacturer, the biopharmaceutical industry is able to respond and share information on the treatment benefits and value with the requestors is critical to the exchange of information to improve patient health.
We also offer the following comments and suggestions to the revised Format:
- Page 7. Comparative Effectiveness: We welcome the addition of tools to aid the critical appraisal of four types of outcomes research (prospective and retrospective observational studies, modeling studies, and indirect treatment comparisons). However, critically appraising individual studies is only one step. Because different study designs have different strengths and limitations, synthesis of the body of evidence is needed. Several existing tools are currently in use by health care decision-makers, including the CER Collaborative endorsed Institute for Clinical and Economic Review (ICER) Evidence Rating Matrix.,, Other methods also exist such as the GRADE process and U.S. Preventive Service Task Force methods.,,
Proposed Change: We suggest the inclusion of at least one existing tool to guide in evidence synthesis.
- Page 16. Product Description- Quality measures: We applaud the inclusion and recognition that biopharmaceuticals, devices, and diagnostics can help achieve quality targets. Quality measures are central to the assessment of value as the health care system moves towards rewarding value. However, it is less clear where manufacturers should place this information within the Format (e.g., within Section 3 or 5) due to various sources from which evidence may be available (e.g., real-world evaluation, modeling studies, or others). It is also unclear where busy health care decision-makers should look for this information.
Proposed Change: We recommend including a specific section on “Impact on Quality” within Section 5.0 when there is a potential for or demonstrated impact on quality measure. If measures do not exist for that condition or product, the manufacturer may note that this section is not applicable.
- Page 22. Primary Clinical Evidence: We applaud the need to conduct studies using high-quality and rigorous standards. However, requiring manufacturers to grade all studies listed in the dossier creates three issues. First, health care decision-makers are likely to discount study quality ratings assessed by manufacturers. For example, one study found that physicians were twice as likely to rate the same hypothetical abstracts as having high quality and credibility when the funding source listed was the National Institutes of Health as compared to industry. Second, there is a lack of agreement on the methods to evaluate the quality of studies. For example, which is needed for grading randomized controlled trials: the 3-item Jadad scale or the more extensive assessments of quality such as the 25-item CONSORT Statement?, Similarly, a recent study by Morton et al found that while many organizations provide guidance on how to evaluate the quality of observational studies, the standards and guidelines for evaluating quality often lack agreement. Depending upon which grading method is selected, studies may be considered flawed by one standard and not by others. Third, the relevance of the study and the certainty of the data and study are dependent upon the population and problem. For instance, a high-quality study conducted in a Scandinavian population assessing hepatitis c cure rates may be less relevant for a health care decision-maker managing a low-income urban population. Similarly, the evidence certainty required for different organizations or decisions (e.g., coverage, reimbursement, formulary placement, policy, care coordination, or quality improvement) may vary and should be fit for the decision purpose. For this reason, the health care decision-maker rather than the biopharmaceutical manufacturer is likely to identify the relevance and credibility and, therefore, study quality required for their organization.
Proposed Change: We recommend deleting the reference to grading all studies listed in the dossier. We recognize that these same methods can be used internally to ensure quality study designs; however, without additional confirmation that manufacturer-rated information would be utilized by health care decision-makers- grading studies is likely to result in excessive time and effort without any impact on patient care. Alternatively, agreement on which grading approaches should be used is needed to ensure that manufacturers and health care decision-makers apply similar ratings.
- Page 14. Economic Benefits: Health care costs are increasingly being shifted to consumers giving more weight to informed consumer choices based on the benefits, potential harms, and costs of treatment alternatives. For many consumers and employers, there is a vested interest in staying healthy and productive. As outlined in the ISPOR 2012 Budget Impact Analysis Good Practice II Task Force, indirect costs may inform private health insurers and employers as they consider whether productivity gains outweigh increased health care costs.
Proposed Change: We suggest noting that indirect costs may be included as an outcome of cost-effectiveness and budget impact models. However, these costs should be reported separately from the direct medical costs.
- Page 17. Approaches to Treatment: We concur with the importance of describing heterogeneity of treatment effects, if any, related to the use of the product and the request for information that substantiate heterogeneity effects. As Warholak et al found, few health care decisions-makers agreed that they had knowledge about heterogeneity assessment methods.
Proposed Change: We recommend citing examples of appropriate methods (e.g., cross-over study designs, n-of-1 studies, subgroup analyses, or other predictive risk modeling methods) to substantiate treatment effect heterogeneity to raise awareness for developers and readers of the Format.
NPC applauds the leadership of the Format Executive Committee to ensure that considerations related to treatment benefit, cost-effectiveness, and affordability are carefully evaluated and balanced when making treatment decisions. NPC looks forward to answering any questions and working as a partner with the Academy of Managed Care Pharmacy to advance the development of good evidence and science for formulary decision-making.
Robert W. Dubois, MD, PhD
Chief Science Officer and Executive Vice President
Jennifer Graff, PharmD
Vice President, Comparative Effectiveness Research
 Ollendorf DA, Pearson SD. An integrated evidence rating to frame comparative effectiveness assessment for decision makers. Med Care. 2010;48(6):S145-52.
 Ollendorf D, Pearson SD. ICER Evidence Rating Matrix: A User’s Guide. Available at: http://www.amcp.org/ICERUserGuide.pdf.
 Synthesizing a Body of Evidence. User Guide and Tool. Available at: https://www.cercollaborative.org/modules/module.aspx?ModuleID=10&CTRL=Page&ContentID=2&ContentTypeID=10.
 GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008; 336:924.
 GRADE 20-part guide. J Clin Epidemiology. 2011. Available at: http://www.gradeworkinggroup.org/publications/JCE_series.htm.
 U.S. Preventive Services Task Force Procedure Manual. December 2015.
 Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1-12.
 CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomized Trials. BMJ. 2010;340.c332.
 Morton SC, Costlow MR, Graff JS, Dubois RW. Standards and guidelines for observational studies: quality is in the eye of the beholder. J Clin Epidemiology. 2015. Published online November 5, 2015. Available at http://www.jclinepi.com/article/S0895-4356(15)00501-6/pdf.
 Sabharwal RK, Graff JS, Holve E, Dubois RW. Developing evidence that is fit for purpose: A framework for payer and research dialogue. Am J Manag Care. 2015;21(9):e545-551.
 Sullivan SD, Mauskopf JA, Augustovski F, et al. Principles of good practice for budget impact analysis II: Report of the ISPOR Task Force on Good Research Practices. Value Health. 2014;17:5-14.
 Warholak TL, Hilgaertner JW, Dean JL et al. Evaluation of an educational program on deciphering heterogeneity for medical coverage decisions. J Manag Care Pharm. 2014;20(6):566-73.
 Willke RJ, Zhen Z, Subedi P, Althin R, Mullins CD. From concepts, theory, and evidence of heterogeneity of treatment effect to methodological approaches: a primer. BMC Med Res Methodol. 2012;12:185.