volume 15, issue 3 - fall 2016 Is Your Practice an Active Community Partner?

Transcription

1 volume 15, issue 3 - fall 2016 Is Your Practice an Active Community Partner?

2 ION Solutions Educational Programs 2017 Meeting Schedule Meeting Date Meeting Name Location Venue January ASH Review Orlando, FL Renaissance Sea World March Oral Therapies Fort Worth, TX Omni September 8-10 National Healthcare Practitioners Charlotte, NC November 3-5 ION National Baltimore, MD Hilton Westin Charlotte All ION Solutions meeting materials are archived on iononline.com. Visit the website to view slides and videos from past meetings. Registration will be available approximately 60 days prior to each event. To register, visit *Meeting dates subject to change.*

3 Oncologistics 3

4 Table of Contents fall Build Referrals and Strengthen Revenues By Vicki Albrecht, Ph.D. Reimbursement Watch ICER Value Framework Takes on NSCLC, Calls Some Agents Overpriced By Aileen Soper 16 What s News at ION 4 Oncologistics

5 volume 15, issue 3 - fall 2016 oneonone with Mark Santos Both patients and physicians benefit when independent community oncology practices thrive. Today, multiple resources are available to help community oncologists maintain success by increasing awareness of their practice, providing the most innovative treatments to their patients and preparing for the future of oncology care. On page six, Vicki Albrecht, Ph.D., senior vice president and general manager of ION Solutions, outlines tactics that oncologists and practice managers can implement to improve efficiency and find more time to spend with patients. A number of organizations have created value frameworks that attempt to define the value of drugs or other medical treatments as a measure of benefits relative to cost. Beginning on page nine, we examine an evidence report by the Institute for Clinical and Economic Review (ICER) regarding treatments for non-small cell lung cancer (NSCLC). At ION Solutions, we believe there is value in community oncology. As the delivery of cancer care evolves, we remain a steadfast partner to support you with integration and innovation to enhance the patient care you provide. Thank you for your continued support. Sincerely, Mark Santos President, ION GPO oncologistics Editorial & Design staff: Chris Vorce Senior Director, Marketing & Communications, ION Solutions Tricia Musslewhite Manager, Marketing & Communications, ION Solutions Sylvia Mugica Manager, Graphic Design, ION Solutions ION Solutions article and advertising submissions: Article submissions and suggestions, as well as advertising inquiries, may be sent to: Tricia Musslewhite Managing Editor, Oncologistics c/o ION Solutions 3101 Gaylord Parkway Frisco, TX Information presented in Oncologistics is not intended as a substitute for the personalized advice given by a healthcare provider. The opinions expressed on the pages of Oncologistics magazine are those of the authors and do not necessarily reflect the views of ION Solutions or AmerisourceBergen Specialty Group. Although Oncologistics strives to present only current and accurate information, readers should not consider it as professional advice or endorsement of any position. Although great care has been taken in compiling and checking the information given in this publication to ensure accuracy, the authors, ION Solutions, and its employees or agents shall not be responsible or in any way liable for the continued currency of the information or for any errors, omissions, or inaccuracies in this magazine, whether arising from negligence or otherwise or for any consequence arising therefrom. The staff of Oncologistics provides columns and other editorial support. In no way are they responsible for the specific views presented in Oncologistics. Oncologistics magazine is published by ION Solutions, an AmerisourceBergen Specialty Group company. All archived issues of Oncologistics are available online at Oncologistics 5

6 Build Referrals and Strengthen Revenues By Vicki Albrecht, Ph.D. 6 Oncologistics

7 When independent community oncology practices thrive, both patients and physicians benefit. Community oncologists who are able to maintain their autonomy can determine not only the best treatment regimen for a particular patient but also the environment in which those patients are treated. Fortunately, multiple resources are available to help community oncologists maintain success by increasing awareness of their practice, providing the most innovative treatments to their patients and preparing for the future of oncology care. In this article, we ll outline tactics that oncologists and practice managers can implement in the short-term to improve efficiency and find more time to spend with patients. Increasing patient referrals statement and associated messaging. This will set the tone about what patients can expect from the practice during treatment. A website with a modern design and robust information can help highlight characteristics that, according to Xcenda market research, patients find most important in a practice. These include specializations within oncology, clinical trial experience and outcomes data how successful is this oncologist at treating their type of cancer? The practice website is only one online channel oncologists should use. Social media is increasingly a resource for patients looking for information about a practice. Facebook, Twitter, LinkedIn and similar venues can be used to educate and engage with patients. In fact, social media can even be used to promote word-of-mouth referrals and add credibility to the practice. It is important to understand the driving forces behind patient referrals because new patients are the lifeblood of any practice. For many practices today, referrals from physicians are the source of many new patients. A few simple activities, such as maintaining an open line of communication, being transparent about pricing and keeping report turnaround times short can foster strong, ongoing relationships with referring physicians. Make it easy for referring physicians to work with you. Oncology practices that are known for streamlined service will naturally be more desirable partners. Engaging a referring physician s office staff and sharing a clear value proposition about how your office can provide high-quality care will ensure your practice is foremost in mind. Beyond solidifying the referral base, practices should find outlets through which they can share their approach to treatment and the value their practice provides to the community. The increasingly competitive oncology marketplace is a challenge but also a compelling reason to invest in marketing. Today, the most common marketing occurs through online channels. An important first step in online marketing can be a refreshed website, as the Web is where many patients look when evaluating where to receive care. The website should serve as the hub for a practice s value proposition and incorporate the mission As more patients enter the practice from increased referrals and better marketing, physicians and practice managers must remain diligent in providing an optimal patient experience while continuing to maintain high-quality, cost-effective care. Two-way communication key to web marketing Marketing online should be coupled with in-person interactions. A practice that is an active community partner will have the opportunity to improve its credibility in an authentic manner not found through online channels. Simple tactics to become an active community partner such as Oncologistics 7

8 sponsoring events, supporting health initiatives or offering educational health programs also can help increase awareness of a community practice. Serving on a board with other influential community members offers another avenue for practitioners to make connections. Over time, the reputation of the community practice will be tied not only to the quality medical care provided but also to regional events and programs that advance health and wellness in the general population. Tracking referrals and increases in traffic will reveal how effectively these initiatives are working and shed light on where to invest marketing and awareness resources in the future. Technology solutions like InfoDive, a business intelligence solution that analyzes internal data and benchmarks against peers, can provide visibility into referral patterns. InfoDive provides practices with heat maps and demographic information to give practice managers and clinicians a deeper look into who they are reaching with their marketing efforts and from where patients are referred. As more patients enter the practice from increased referrals and better marketing, physicians and practice managers must remain diligent in providing an optimal patient experience while continuing to maintain high-quality, costeffective care. The ideal approach to creating efficiency is for physicians and practice managers to use data to identify areas for opportunity and/or improvement. If feasible, a great approach is to work with partners who blend oncology expertise with business intelligence tools and resources in order to identify tactics and resources that will help improve operations and ensure regular, reliable reimbursement. There are a few key questions to ask when evaluating financial efficiencies: How quickly are claims sent to the payer? How quickly does the payer make payment? How often are claims denied? The answers to these questions may identify revenue cycle inefficiencies that take valuable time out of the clinician s schedule. For each area of friction, practice managers or business coaches should start solving for trends rather than solving for each individual issue. Reimbursement, however, is a two-way street. Keep in mind that patients also are affected by the changing reimbursement landscape and often are not aware of programs that can offer financial support. Practices can As an active community partner, the staff and patients of NSHOA Cancer Center participate in numerous events to raise funds for organizations throughout Long Island, N.Y. engage reimbursement counselors to work directly with patients and physicians to help find appropriate access and financial support. Manufacturer support programs can be found through several outlets, including foundations and directly from specialty pharmacies where patients may receive their treatment. Providing tailored resources for patients to afford the costs associated with treatment can lower financial stress, remove the cost barrier and maintain practice health by ensuring appropriate payment. The road ahead for community practices requires both the personalized care physicians are known for and business know-how. There are resources to help practices raise awareness of the value of community oncology, negotiate fair reimbursement and capture more revenue. Recently, a network of oncologists came together to share these types of resources under the name Innovation Cancer. Practices that join Innovation Cancer have access to business coaches, technology to support changes and marketing resources to build a practice s reputation. The business coaches can evaluate a practice s financial health, identify problem areas and help the practice implement a process to better support outstanding accounts receivable issues. The end benefit can be increased strength to secure patients and put more resources toward optimal care. Vicki Albrecht, Ph.D., is senior vice president and general manager of ION Solutions. This article originally was published August 12, 2016, at 8 Oncologistics

9 Reimbursement Watch ICER Value Framework Takes on NSCLC By Aileen Soper A number of organizations have created so-called value frameworks that attempt to define the value of drugs or other medical treatments as a measure of benefits relative to cost. So far a variety of frameworks have been released including ones from the American Society of Clinical Oncology (ASCO), the Institute for Clinical and Economic Review (ICER), the National Comprehensive Cancer Network (NCCN) and Memorial Sloan Kettering. The frameworks have some variation in the methods they use for measuring value but they do have some things or concepts in common including: 1 They consider health outcomes like efficacy or safety They rely on evidence to measure the effect of a given treatment on the outcome They try to merge all of the outcomes into a single measure of health benefit They look to correlate the cost of care with the health benefit Oncologistics 9

10 The oncology community should continue submitting comments to ensure that their perspectives are heard. As the post-comment period evidence reports become available, it will be critical to understand the assessment methodologies used and how they formulated their conclusions. Some drugs are overpriced ICER recently released an evidence report on treatments for non-small cell lung cancer (NSCLC), making it one of that organization s first such efforts to compare treatments for a specific oncology indication. ICER has previously looked at screening tools for breast and colon cancer, and treatments for prostate cancer, multiple myeloma and palliative care. The NSCLC evidence report reflects changes that were made based on comments received from stakeholders in August The assessment analyzes the clinical effectiveness and comparative value, including long-term cost-effectiveness and potential budget impact, of the drugs under study. affordability and require policy discussions around steps that could be taken to manage their costs. The report was not without controversy. Some stakeholders voiced concern that the ICER report might have the effect of limiting patient access to life-sustaining therapy and stifle the trend toward more personalized medicine and targeted treatments with a one-size-fits-all approach. Because cancer cells are able to evade and adapt to various treatments, and may develop other mutations, it is imperative NSCLC patients have several treatment options, according to an opinion piece published by the Pharmaceutical Research and Manufacturers of America (PhRMA). This allows patients to switch to another medicine when their current treatment no longer works. It is also why the framework from [ICER] is concerning. Earlier in the process, groups such as the patient advocacy organization LUNGevity voiced concerns that patients and lung cancer clinicians were not included in the development of the scoping document for the NSCLC study, meaning that it would not reflect how treatments are being used and what patients value. The group also noted the study did not differentiate by histology or consider that lung cancer is a collection of rare diseases and subpopulations with varied not homogenous needs. Further, the report did not consider the rapid advances happening in treatment of NSCLC, the group argued. The report found that targeted regimens for first- and second-line use in NSCLC appears to confer clinical benefits in terms of lengthening progression-free and overall survival as well as improved quality of life. ICER also used the results of the analysis to calculate a valuebased price benchmark. Study authors concluded that at current wholesale acquisition costs, the estimated cost-effectiveness of tyrosine kinase inhibitors (including GILOTRIF [afatinib], TARCEVA [erlotinib], and IRESSA [gefitinib]) appears to fall within commonly-accepted thresholds. The cost-effectiveness of programmed death 1 receptor immunotherapies (including OPDIVO [nivolumab], KEYTRUDA [pembrolizumab], and TECENTRIQ [atezolizumab]) exceeds those thresholds, though authors admitted greater uncertainty in the findings due to variability in the estimates of overall and progression-free survival. 2 In addition, ICER also considered whether the introduction of these agents might pose challenges to health system The potential impacts Despite the widespread attention brought to ICER s studies, many payers are not yet incorporating them into formulary decision making. So far, clinical efficacy, comparative safety and competitive pricing via rebates and contract negotiations continue to be more powerful influences. As ICER moves forward with performing these assessments, the oncology community should continue submitting comments to ensure that their perspectives are heard. As the post-comment period evidence reports become available, it will be critical to understand the assessment methodologies used and how they formulated their conclusions. ICER will release its plans for reviews in 2017 later this fall and it will be useful to track any plans to review additional treatments for oncology and hematology. 10 Oncologistics

11 What is ICER s Value Assessment and Framework? 3 An objective method to calculate a value-based price benchmark for therapies reviewed Serves as a way to categorize and integrate various conceptual elements into judgments of two different aspects of value: care value and provisional health system value Weighs the following in making an overall determination of value: Comparative Clinical Effectiveness Comparative clinical effectiveness reflects a joint judgment of the size of the comparative net health benefit and how sure ICER is about the evidence. Other Benefits or Disadvantages Benefits or disadvantages offered by the intervention to the individual patient, caregivers, the delivery system, other patients, or the public that would not have been considered as part of the evidence on comparative clinical effectiveness. Contextual Considerations Contextual considerations include ethical, legal, or other issues that influence the relative priority of illnesses and interventions. Care Value Care value is determined by looking at: comparative clinical effectiveness, incremental costs per outcomes achieved, other benefits or disadvantages, and contextual considerations. Care value represents the long-term perspective, at the individual patient level, on patient benefits and the incremental costs to achieve those benefits. Potential Budget Impact Estimated net change in total health care costs over a five-year timeframe. Provisional Health System Value Provisional health system value represents a judgment integrating consideration of the long-term care value of a new intervention with an analysis of its potential shortterm budget impact if utilization is unmanaged. Mechanisms to Maximize Health System Value Maximizing health system value is an action step, ideally supported by enhanced early dialogue among multiple stakeholders. Learn more: Chandra A, Shafrin A, Dhawan R. Utility of cancer value frameworks for patients, payers, and physicians. JAMA. 2016;315(19): Accessed October 16, ICER. Non-small cell lung cancer: evidence report. Accessed October 16, ICER. Assessing Value. Accessed October 18, Aileen Soper is assistant director, Reimbursement Strategy and Tactics, with Xcenda. Oncologistics 11

12 EXTEND EFFICACY. EXTEND THE POSSIBILITIES. The approval of the NINLARO (ixazomib) regimen (NINLARO+lenalidomide+dexamethasone) was based on a statistically significant ~6 month improvement in median progression-free survival vs the placebo regimen (placebo+lenalidomide+ dexamethasone) (median: 20.6 vs 14.7 months [95% CI, 17.0-NE and 95% CI, , respectively]; HR=0.74 [95% CI, ]; P=0.012). The NINLARO regimen demonstrated rapid responses Median time to initial response (months) NINLARO regimen 1.1 Placebo+len+dex 1.9 Depth of response in the NINLARO and placebo regimens ORR*: 78% vs 72%; CR: 12% vs 7%; VGPR+CR: 48% vs 39%; and PR: 30% vs 33%, respectively *ORR=CR+PR, including VGPR. ARs=adverse reactions; CR=complete response; ORRs=overall response rates; PR=partial response; VGPR=very good partial response. TOURMALINE-MM1: a global, phase 3, randomized (1:1), double-blind, placebo-controlled study that evaluated the safety and efficacy of NINLARO (an oral proteasome inhibitor) vs placebo, both in combination with lenalidomide and dexamethasone, until disease progression or unacceptable toxicity in 722 patients with relapsed and/or refractory multiple myeloma who received 1-3 prior therapies. IMPORTANT SAFETY INFORMATION FOR NINLARO WARNINGS AND PRECAUTIONS Thrombocytopenia has been reported with NINLARO. During treatment, monitor platelet counts at least monthly, and consider more frequent monitoring during the first three cycles. Manage thrombocytopenia with dose modifications and platelet transfusions as per standard medical guidelines. Adjust dosing as needed. Platelet nadirs occurred between Days of each 28-day cycle and recovered to baseline by the start of the next cycle. Gastrointestinal Toxicities, including diarrhea, constipation, nausea and vomiting, were reported with NINLARO and may occasionally require the use of antidiarrheal and antiemetic medications, and supportive care. Diarrhea resulted in the discontinuation of one or more of the three drugs in 1% of patients in the NINLARO regimen and < 1% of patients in the placebo regimen. Adjust dosing for severe symptoms. Peripheral Neuropathy (predominantly sensory) was reported with NINLARO. The most commonly reported reaction was peripheral sensory neuropathy (19% and 14% in the NINLARO and placebo regimens, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1%). Peripheral neuropathy resulted in discontinuation of one or more of the three drugs in 1% of patients in both regimens. Monitor patients for symptoms of peripheral neuropathy and adjust dosing as needed. Peripheral Edema was reported with NINLARO. Monitor for fluid retention. Investigate for underlying causes when appropriate and provide supportive care as necessary. Adjust dosing of dexamethasone per its prescribing information or NINLARO for Grade 3 or 4 symptoms. Takeda Oncology and are registered trademarks of Takeda Pharmaceutical Company Limited. NINLARO is a registered trademark of Millennium Pharmaceuticals, Inc. Copyright 2016, Millennium Pharmaceuticals, Inc. All rights reserved. Printed in USA 7/16 USO/IXA/16/0157

13 INDICATION: NINLARO is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Nonhematologic ARs occurring in 5% of patients with a 5% difference between the NINLARO regimen (n=360) and the placebo regimen (n=360) All grades, grade 3 (respectively): upper respiratory (19%, <1% vs 14%, <1%), peripheral neuropathies (28%, 2% vs 21%, 2%), diarrhea (42%, 6% vs 36%, 2%), constipation (34%, <1% vs 25%, <1%), nausea (26%, 2% vs 21%, 0%), vomiting (22%, 1% vs 11%, <1%), rash (19%, 3% vs 11%, 1%), back pain (21%, <1% vs 16%, 3%), peripheral edema (25%, 2% vs 18%, 1%) Grade 4 ARs occurring in 5% of patients with a 5% difference between the 2 regimens were 0% Pooled hematologic adverse events and laboratory data Incidence of thrombocytopenia in patients in the NINLARO and placebo regimens: all grades, 78% and 54%; grades 3-4, 26% vs 11%, respectively Incidence of neutropenia: all grades, 67% vs 66%; grades 3-4, 26% vs 30%, respectively Represents a pooling of preferred terms. The NINLARO regimen represented a sustainable treatment for patients Discontinuation rates of the full regimen due to ARs 1 13% 11% NINLARO regimen (n=360) Placebo+len+dex (n=360) Discontinuation rates were low and comparable with the NINLARO and placebo regimens. 80% of patients continued at the starting dose of NINLARO without dose reduction 1 Now under contract with your GPO Learn more about NINLARO at NINLAROhcp.com. WARNINGS AND PRECAUTIONS (continued) Cutaneous Reactions: Rash, most commonly maculopapular and macular rash, was reported with NINLARO. Rash resulted in discontinuation of one or more of the three drugs in < 1% of patients in both regimens. Manage rash with supportive care or with dose modification. Hepatotoxicity has been reported with NINLARO. Druginduced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic and hepatotoxicity have each been reported in < 1% of patients treated with NINLARO. Events of liver impairment have been reported (6% in the NINLARO regimen and 5% in the placebo regimen). Monitor hepatic enzymes regularly during treatment and adjust dosing as needed. Embryo-fetal Toxicity: NINLARO can cause fetal harm. Women should be advised of the potential risk to a fetus, to avoid becoming pregnant, and to use contraception during treatment and for an additional 90 days after the final dose of NINLARO. REFERENCE: 1. Data on File 117, Takeda Pharmaceuticals International Co. ADVERSE REACTIONS The most common adverse reactions ( 20%) in the NINLARO regimen and greater than the placebo regimen, respectively, were diarrhea (42%, 36%), constipation (34%, 25%), thrombocytopenia (78%, 54%; pooled from adverse events and laboratory data), peripheral neuropathy (28%, 21%), nausea (26%, 21%), peripheral edema (25%, 18%), vomiting (22%, 11%), and back pain (21%, 16%). Serious adverse reactions reported in 2% of patients included thrombocytopenia (2%) and diarrhea (2%). SPECIAL POPULATIONS Hepatic Impairment: Reduce the NINLARO starting dose to 3 mg in patients with moderate or severe hepatic impairment. Renal Impairment: Reduce the NINLARO starting dose to 3 mg in patients with severe renal impairment or end-stage renal disease requiring dialysis. NINLARO is not dialyzable. Lactation: Advise women to discontinue nursing while on NINLARO. DRUG INTERACTIONS: Avoid concomitant administration of NINLARO with strong CYP3A inducers. Please see adjacent Brief Summary.

14 BRIEF SUMMARY OF PRESCRIBING INFORMATION NINLARO (ixazomib) capsules, for oral use 1 INDICATION NINLARO (ixazomib) is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. 5 WARNINGS AND PRECAUTIONS 5.1 Thrombocytopenia: Thrombocytopenia has been reported with NINLARO with platelet nadirs typically occurring between Days of each 28-day cycle and recovery to baseline by the start of the next cycle. Three percent of patients in the NINLARO regimen and 1% of patients in the placebo regimen had a platelet count 10,000/mm 3 during treatment. Less than 1% of patients in both regimens had a platelet count 5000/mm 3 during treatment. Discontinuations due to thrombocytopenia were similar in both regimens (< 1% of patients in the NINLARO regimen and 2% of patients in the placebo regimen discontinued one or more of the three drugs). The rate of platelet transfusions was 6% in the NINLARO regimen and 5% in the placebo regimen. Monitor platelet counts at least monthly during treatment with NINLARO. Consider more frequent monitoring during the first three cycles. Manage thrombocytopenia with dose modifications and platelet transfusions as per standard medical guidelines. 5.2 Gastrointestinal Toxicities: Diarrhea, constipation, nausea, and vomiting, have been reported with NINLARO, occasionally requiring use of antidiarrheal and antiemetic medications, and supportive care. Diarrhea was reported in 42% of patients in the NINLARO regimen and 36% in the placebo regimen, constipation in 34% and 25%, respectively, nausea in 26% and 21%, respectively, and vomiting in 22% and 11%, respectively. Diarrhea resulted in discontinuation of one or more of the three drugs in 1% of patients in the NINLARO regimen and < 1% of patients in the placebo regimen. Adjust dosing for Grade 3 or 4 symptoms. 5.3 Peripheral Neuropathy: The majority of peripheral neuropathy adverse reactions were Grade 1 (18% in the NINLARO regimen and 14% in the placebo regimen) and Grade 2 (8% in the NINLARO regimen and 5% in the placebo regimen). Grade 3 adverse reactions of peripheral neuropathy were reported at 2% in both regimens; there were no Grade 4 or serious adverse reactions. The most commonly reported reaction was peripheral sensory neuropathy (19% and 14% in the NINLARO and placebo regimen, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1%). Peripheral neuropathy resulted in discontinuation of one or more of the three drugs in 1% of patients in both regimens. Patients should be monitored for symptoms of neuropathy. Patients experiencing new or worsening peripheral neuropathy may require dose modification. 5.4 Peripheral Edema: Peripheral edema was reported in 25% and 18% of patients in the NINLARO and placebo regimens, respectively. The majority of peripheral edema adverse reactions were Grade 1 (16% in the NINLARO regimen and 13% in the placebo regimen) and Grade 2 (7% in the NINLARO regimen and 4% in the placebo regimen). Grade 3 peripheral edema was reported in 2% and 1% of patients in the NINLARO and placebo regimens, respectively. There was no Grade 4 peripheral edema reported. There were no discontinuations reported due to peripheral edema. Evaluate for underlying causes and provide supportive care, as necessary. Adjust dosing of dexamethasone per its prescribing information or NINLARO for Grade 3 or 4 symptoms. 5.5 Cutaneous Reactions: Rash was reported in 19% of patients in the NINLARO regimen and 11% of patients in the placebo regimen. The majority of the rash adverse reactions were Grade 1 (10% in the NINLARO regimen and 7% in the placebo regimen) or Grade 2 (6% in the NINLARO regimen and 3% in the placebo regimen). Grade 3 rash was reported in 3% of patients in the NINLARO regimen and 1% of patients in the placebo regimen. There were no Grade 4 or serious adverse reactions of rash reported. The most common type of rash reported in both regimens included maculo-papular and macular rash. Rash resulted in discontinuation of one or more of the three drugs in < 1% of patients in both regimens. Manage rash with supportive care or with dose modification if Grade 2 or higher. 5.6 Hepatotoxicity: Drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic and hepatotoxicity have each been reported in < 1% of patients treated with NINLARO. Events of liver impairment have been reported (6% in the NINLARO regimen and 5% in the placebo regimen). Monitor hepatic enzymes regularly and adjust dosing for Grade 3 or 4 symptoms. 5.7 Embryo-Fetal Toxicity: NINLARO can cause fetal harm when administered to a pregnant woman based on the mechanism of action and findings in animals. There are no adequate and well-controlled studies in pregnant women using NINLARO. Ixazomib caused embryo-fetal toxicity in pregnant rats and rabbits at doses resulting in exposures that were slightly higher than those observed in patients receiving the recommended dose. Females of reproductive potential should be advised to avoid becoming pregnant while being treated with NINLARO. If NINLARO is used during pregnancy or if the patient becomes pregnant while taking NINLARO, the patient should be apprised of the potential hazard to the fetus. Advise females of reproductive potential that they must use effective contraception during treatment with NINLARO and for 90 days following the final dose. 6 ADVERSE REACTIONS The following adverse reactions are described in detail in other sections of the prescribing information: Thrombocytopenia [see Warnings and Precautions (5.1)] Gastrointestinal Toxicities [see Warnings and Precautions (5.2)] Peripheral Neuropathy [see Warnings and Precautions (5.3)] Peripheral Edema [see Warnings and Precautions (5.4)] Cutaneous Reactions [see Warnings and Precautions (5.5)] Hepatotoxicity [see Warnings and Precautions (5.6)] 6.1 CLINICAL TRIALS EXPERIENCE Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety population from the randomized, double-blind, placebo-controlled clinical study included 720 patients with relapsed and/or refractory multiple myeloma, who received NINLARO in combination with lenalidomide and dexamethasone (NINLARO regimen; N=360) or placebo in combination with lenalidomide and dexamethasone (placebo regimen; N=360). The most frequently reported adverse reactions ( 20%) in the NINLARO regimen and greater than the placebo regimen were diarrhea, constipation, thrombocytopenia, peripheral neuropathy, nausea, peripheral edema, vomiting, and back pain. Serious adverse reactions reported in 2% of patients included thrombocytopenia (2%) and diarrhea (2%). For each adverse reaction, one or more of the three drugs was discontinued in 1% of patients in the NINLARO regimen. Table 4: Non-Hematologic Adverse Reactions Occurring in 5% of Patients with a 5% Difference Between the NINLARO Regimen and the Placebo Regimen (All Grades, Grade 3 and Grade 4) System Organ Class / Preferred Term Infections and infestations Upper respiratory tract infection NINLARO + Lenalidomide and Dexamethasone N=360 All Placebo + Lenalidomide and Dexamethasone N=360 N (%) N (%) Grade 3 Grade 4 All Grade 3 Grade 4 69 (19) 1 (< 1) 0 52 (14) 2 (< 1) 0 Nervous system disorders Peripheral neuropathies* 100 (28) 7 (2) 0 77 (21) 7 (2) 0 Gastrointestinal disorders Diarrhea Constipation Nausea Vomiting 151 (42) 122 (34) 92 (26) 79 (22) 22 (6) 1 (< 1) 6 (2) 4 (1) (36) 90 (25) 74 (21) 38 (11) 8 (2) 1 (< 1) 0 2 (< 1) Skin and subcutaneous tissue disorders Rash* 68 (19) 9 (3) 0 38 (11) 5 (1) 0 Musculoskeletal and connective tissue disorders Back pain 74 (21) 2 (< 1) 0 57 (16) 9 (3) 0 General disorders and administration site conditions Edema peripheral 91 (25) 8 (2) 0 66 (18) 4 (1) 0 Note: Adverse reactions included as preferred terms are based on MedDRA version *Represents a pooling of preferred terms (Continued on next page)

15 Brief Summary (cont d) Table 5: Thrombocytopenia and Neutropenia (pooled adverse event and laboratory data) NINLARO + Lenalidomide and Dexamethasone N=360 Placebo + Lenalidomide and Dexamethasone N=360 N (%) N (%) Any Grade Grade 3-4 Any Grade Grade 3-4 Thrombocytopenia 281 (78) 93 (26) 196 (54) 39 (11) Neutropenia 240 (67) 93 (26) 239 (66) 107 (30) Eye Disorders Eye disorders were reported with many different preferred terms but in aggregate, the frequency was 26% in patients in the NINLARO regimen and 16% of patients in the placebo regimen. The most common adverse reactions were blurred vision (6% in the NINLARO regimen and 3% in the placebo regimen), dry eye (5% in the NINLARO regimen and 1% in the placebo regimen), and conjunctivitis (6% in the NINLARO regimen and 1% in the placebo regimen). Grade 3 adverse reactions were reported in 2% of patients in the NINLARO regimen and 1% in the placebo regimen. The following serious adverse reactions have each been reported at a frequency of < 1%: acute febrile neutrophilic dermatosis (Sweet s syndrome), Stevens-Johnson syndrome, transverse myelitis, posterior reversible encephalopathy syndrome, tumor lysis syndrome, and thrombotic thrombocytopenic purpura. 7 DRUG INTERACTIONS 7.1 Strong CYP3A Inducers: Avoid concomitant administration of NINLARO with strong CYP3A inducers (such as rifampin, phenytoin, carbamazepine, and St. John s Wort). 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy: Women should avoid becoming pregnant while being treated with NINLARO. Risk Summary: NINLARO can cause fetal harm when administered to a pregnant woman. There are no human data available regarding the potential effect of NINLARO on pregnancy or development of the embryo or fetus. Ixazomib caused embryo-fetal toxicity in pregnant rats and rabbits at doses resulting in exposures that were slightly higher than those observed in patients receiving the recommended dose. Advise women of the potential risk to a fetus and to avoid becoming pregnant while being treated with NINLARO. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Animal Data: In an embryo-fetal development study in pregnant rabbits there were increases in fetal skeletal variations/abnormalities (caudal vertebrae, number of lumbar vertebrae, and full supernumerary ribs) at doses that were also maternally toxic ( 0.3 mg/kg). Exposures in the rabbit at 0.3 mg/kg were 1.9 times the clinical time averaged exposures at the recommended dose of 4 mg. In a rat dose range-finding embryo-fetal development study, at doses that were maternally toxic, there were decreases in fetal weights, a trend towards decreased fetal viability, and increased post-implantation losses at 0.6 mg/kg. Exposures in rats at the dose of 0.6 mg/kg was 2.5 times the clinical time averaged exposures at the recommended dose of 4 mg. 8.2 Lactation: It is not known whether NINLARO or its metabolites are present in human milk. Many drugs are present in human milk and as a result, there could be a potential for adverse events in nursing infants. Advise women to discontinue nursing. 8.3 Females and Males of Reproductive Potential: Contraception - Male and female patients of childbearing potential must use effective contraceptive measures during and for 90 days following treatment. Infertility - Fertility studies were not conducted with NINLARO; however there were no effects on reproductive organs in either males or females in nonclinical studies in rats and dogs. 8.4 Pediatric Use: Safety and effectiveness have not been established in pediatric patients. 8.5 Geriatric Use: Of the total number of subjects in clinical studies of NINLARO, 55% were 65 and over, while 17% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. 8.6 Hepatic Impairment: In patients with moderate or severe hepatic impairment, the mean AUC increased by 20% when compared to patients with normal hepatic function. Reduce the starting dose of NINLARO in patients with moderate or severe hepatic impairment. 8.7 Renal Impairment: In patients with severe renal impairment or ESRD requiring dialysis, the mean AUC increased by 39% when compared to patients with normal renal function. Reduce the starting dose of NINLARO in patients with severe renal impairment or ESRD requiring dialysis. NINLARO is not dialyzable and therefore can be administered without regard to the timing of dialysis. 10 OVERDOSAGE: There is no known specific antidote for NINLARO overdose. In the event of an overdose, monitor the patient for adverse reactions and provide appropriate supportive care. 17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Dosing Instructions Instruct patients to take NINLARO exactly as prescribed. Advise patients to take NINLARO once a week on the same day and at approximately the same time for the first three weeks of a four week cycle. Advise patients to take NINLARO at least one hour before or at least two hours after food. Advise patients that NINLARO and dexamethasone should not be taken at the same time, because dexamethasone should be taken with food and NINLARO should not be taken with food. Advise patients to swallow the capsule whole with water. The capsule should not be crushed, chewed or opened. Advise patients that direct contact with the capsule contents should be avoided. In case of capsule breakage, avoid direct contact of capsule contents with the skin or eyes. If contact occurs with the skin, wash thoroughly with soap and water. If contact occurs with the eyes, flush thoroughly with water. If a patient misses a dose, advise them to take the missed dose as long as the next scheduled dose is 72 hours away. Advise patients not to take a missed dose if it is within 72 hours of their next scheduled dose. If a patient vomits after taking a dose, advise them not to repeat the dose but resume dosing at the time of the next scheduled dose. Advise patients to store capsules in original packaging, and not to remove the capsule from the packaging until just prior to taking NINLARO. Thrombocytopenia: Advise patients that they may experience low platelet counts (thrombocytopenia). Signs of thrombocytopenia may include bleeding and easy bruising. Gastrointestinal Toxicities: Advise patients they may experience diarrhea, constipation, nausea and vomiting and to contact their physician if these adverse reactions persist. Peripheral Neuropathy: Advise patients to contact their physicians if they experience new or worsening symptoms of peripheral neuropathy such as tingling, numbness, pain, a burning feeling in the feet or hands, or weakness in the arms or legs. Peripheral Edema: Advise patients to contact their physicians if they experience unusual swelling of their extremities or weight gain due to swelling. Cutaneous Reactions: Advise patients to contact their physicians if they experience new or worsening rash. Hepatotoxicity: Advise patients to contact their physicians if they experience jaundice or right upper quadrant abdominal pain. Pregnancy: Advise women of the potential risk to a fetus and to avoid becoming pregnant while being treated with NINLARO and for 90 days following the final dose. Advise patients to contact their physicians immediately if they or their female partner become pregnant during treatment or within 90 days of the final dose. Concomitant Medications: Advise patients to speak with their physicians about any other medication they are currently taking and before starting any new medications. Please see full Prescribing Information for NINLARO at NINLARO-hcp.com. NINLARO is a registered trademark of Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc. is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited Millennium Pharmaceuticals, Inc v2 USO/IXA/15/0123(2)

16 What s News at ION USP 800 What We Know Today Both federal and state governments are looking at measures to more tightly regulate the practice of sterile compounding, one of which is through adoption of USP 800. ION Solutions believes that the implementation of USP 800, as currently written, poses distinct barriers to the ability of patients to obtain treatment from their physicians. ION Solutions also believes that community oncology should be exempt from USP 800, as the FDA excludes the following from the definition of compounding: Compounding does not include mixing, reconstituting or similar acts that are performed in accordance with the directions contained in approved labeling provided by the product s manufacturer and other manufacturer directions consistent with that labeling. In those states that have considered implementation of USP 800 as written, despite the above guidance from the FDA, education and lobbying efforts have helped physicians obtain key relief from USP 800 oversight. This relief has enabled them to continue to prepare certain medications for administration to their patients, which would otherwise meet the definition of sterile compounding and fall under USP 800. Our recommendation is to work with your local and state governmental agencies to ensure your patients access to treatment does not become subject to the otherwise burdensome requirements of USP 800. There are a number of things you can do to get involved: Contact the agency who has responsibility for oversight of your practice (i.e. Board of Medicine). Contact the agency that is contemplating the adoption of any new sterile compounding regulations. Those agencies may extend from the Board of Medicine or Pharmacy, the state OSHA agency or possibly down to the local county board of health. If the overseeing agency intends to adopt new sterile compounding regulations, initiate a dialogue on how the contemplated sterile compounding regulations negatively impacts patient access to obtaining needed treatment and how you may gain an exemption from the requirements. Reach out to your state legislative representatives so they can advocate on your behalf. Also, note that USP itself isn t a governmental body. In order for compliance to be mandatory, a federal/state legislature or agency must adopt the relevant USP standard. Getting involved in advocacy by helping to educate the relevant governmental entities on the impact of any proposed new sterile compounding laws/regulations has proved to be community oncology s best course of action. Contact your ION strategic accounts manager (SAM) for more information on what you can do to get involved. 16 Oncologistics

17 SON Dashboard Provides Analytics Insight for In-Office Dispensing Programs ION Solutions Specialty Oncology Network (SON) members now have access to the SON Dashboard, an innovative tool designed to give community oncologists the information they need to manage the operational flow of dispensing, adapt to dispensing trends and enhance patient care. With the SON Dashboard you can: Monitor key metrics to improve operations and profitability Evaluate and improve practice workflow to increase capture rates Assess specialty percentage by payer Understand prescription retention Manage compliance to contracts Identify Medicare and commercial dispenses To learn how to add the SON Dashboard to your dispensing program, talk to your clinical practice consultant. If you would like to learn more about SON, the leader in the oral dispensing space with 255 dispensing sites, talk to your SAM or Preparing your Practice for MIPS With MACRA and the quality-based reimbursement measures proposed to go into effect on Jan. 1 for nearly all physicians who accept Medicare, practices need to become familiar with what is to come. CMS says that most physician practices will have to choose the MIPS pathway (Merit-Based Incentive Payment System) in order to be reimbursed for Medicare patients. To view our webinar series, Preparing Your Practice for MIPS, visit click on Meetings and Webcasts and go to the Webcast Archives. Is your practice prepared? Some of the general considerations practices should address (as outlined by the AMA and ASCO): You are exempt from MIPS participation if you have $10,000 or less in Medicare charges and 100 or fewer Medicare patients annually or you are in your first year of Medicare Part B participation If you are not already participating in a patient clinical data registry, contact your specialty society about participating in theirs data registries can streamline reporting Be sure your practice is reporting for the Physician Quality Reporting System (PQRS) and Meaningful Use (MU) Physicians in a practice of more than one eligible clinician should decide whether to report individually or as a group Review your Quality and Resource Use Report (QRUR), which determines your Value-Based Payment Modifier (Value Modifier) score (See page 18) Even with information from different medical societies, the ever-changing rules and acronyms can be difficult to understand. With PQRS, MU and the Value Modifier all merged into MIPS, practices need to understand the changes. ION Solutions will be offering more information on how practices can submit quality data and does offer assistance looking at current practice processes to help achieve those quality measures, as well as assistance in reporting for the proposed MACRA program. Oncologistics 17

18 Accessing your QRUR What is a QRUR? CMS established the Quality and Resource Use Report (QRUR) to provide physicians with comparative information about the quality and cost of care for their Medicare patients. Information in the reports comes from PQRS and claims data and are compared across similar specialties on data provided in the previous year. Through its Physician Feedback Program, CMS produces QRURs for all solo physicians and physician groups that have billed Medicare Part B FFS during the reporting year. The QRUR includes information regarding performance on quality and cost of care measures delivered to patients. It is a part of CMS effort to move physician payment toward a system that rewards value over volume. The QRUR analyzes performance at the Tax Identification Number (TIN) level. The report includes performance information from measures reported through the Physician Quality Reporting System (PQRS) and uses Medicare claims to calculate additional quality outcome measures and cost measures. Data in the QRUR is used to calculate your Value Modifier and subsequent payment adjustments (positive, negative, or neutral). In September, CMS made available the 2015 QRURs and the information shown in them determine how CMS calculates the 2017 Value Modifier with downward, upward or neutral adjustments (for 10 or more eligible professionals in a practice only). For those practices with nine or fewer EPs, a neutral or upward adjustment will be made, as long as PQRS is reported successfully. The annual QRUR provides comprehensive information from the reporting period (January December). CMS provides QRURs as a means to help physicians and groups understand the care they deliver to Medicare beneficiaries and identify opportunities for improvement in that care. Reviewing your practice s QRUR gives you information that can help your practice maximize payments now and in the future. It is CMS hope that practices take the information from the report to see practice care patterns and see actionable items that will help your practice improve care and reduce costs at the same time. There are two reports each year a mid-year QRUR, which is informational only, and the annual QRUR, which used information from January December along with the CMS-calculated quality and cost measures. How do I see my QRUR? QRURs are available at the TIN level and accessed via the CMS Enterprise Portal (portal.cms.gov) by authorized individuals of solo or group practices. Each TIN needs a designated Security Official, or in the case of solo practices an Individual Practitioner. This role is acquired through the CMS Enterprise Identity Management (EIDM) system. The process to access a QRUR can be difficult to navigate. CMS offers a quick reference guide with screenshots that walks you through the process. You may contact the QualityNet Help Desk at qnetsupport@hcqis.org or for assistance with EIDM accounts. 18 Oncologistics

19 We Support the Health of your Practice With the Same Dedication that You Support Your Patients Your number one priority is the health of your patients. With the changing healthcare landscape, our number one priority is the business health of your practice. Dedicated exclusively to the viability of community oncology, ION Solutions provides contracting, technology, education and advocacy support that ensures you have the tools to run your practice both efficiently and effectively. With the practice support of ION Solutions, you can navigate this changing environment and focus on providing quality care for your patients. To learn how ION Solutions enables community oncology practices to improve operational efficiency, financial performance and quality of care, contact your Strategic Account Manager or visit IONonline.com. To experience ION Solutions advocacy support, visit ourcommunitycounts.org.

20 Shrinking margins have pushed independent specialty practices to place even greater focus on operational efficiency. In response, successful practices have turned to their GPO and distribution partner for customized inventory management, as well as integrated technologies and business consulting, to increase time with patients. Improving cash flow takes a streamlined workflow. It takes AmerisourceBergen. ItTakesAmerisourceBergen.com SPECIALTY DISTRIBUTION \ GPO SERVICES \ TECHNOLOGY AND BUSINESS CONSULTING \ SPECIALTY PHARMACY