Risk-Based Compliance Monitoring Sample Sizes and Selection Methodology

Transcription

1 Risk-Based Compliance Monitoring Sample Sizes and Selection Methodology March 17, 2016

2 Disclaimer Independent Commercial Compliance is a full service compliance agency focusing on sales and marketing activities and enforcement within company compliance policy in the United States. ICC does not provide legal or scientific advice or review. We offer our opinion, comments and recommendations as guidance only for consideration in the development of pharmaceutical manufacturer product presentations and promotional activities. Nothing contained herein shall be considered legal advice. Individual pharmaceutical manufacturers are solely responsible for ensuring that the product label and marketing activities are truthful, non-misleading, and fairly balanced and for seeking legal advice from their own legal counsel, including legal counsel specializing in FDA and FTC regulatory compliance.

3 Monitoring Sample Sizes - Selection Methodology Appropriate Sample Sizes What is the correct percentage of promotional events to monitor?

4 Monitoring Sample Sizes - Selection Methodology Appropriate Sample Sizes What is the correct percentage of promotional events to monitor? It Depends

5 What is the correct percentage of promotional events to monitor? 1. Environmental Factors Public Perception Congressional Pricing Inquiry Election Year Commentary AKS Individual Prosecutions via Speaker Fees 2. Internal Factors Volume of Speaker Programs; Size of Sales Force Speaker Programs In Office Venue Based» Appearance of Kickbacks Product Risk Assessment Factors Disease State Competitive Environment Off Label Potential Price

6 What is the correct percentage of promotional events to monitor? 1. Environmental Factors Public Perception Congressional Pricing Inquiry Election Year Commentary AKS Individual Prosecutions via Speaker Fees 2. Internal Factors Volume of Speaker Programs; Size of Sales Force Speaker Programs In Office Venue Based» Appearance of Kickbacks Product Risk Assessment Factors Disease State Competitive Environment Off Label Potential Price

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9 Congressional Pricing Inquiry Senate committee investigating large drug price increases These companies are to ethical pharmaceutical companies as a loan shark is to a bank, said Senator Susan Collins, Republican of Maine Turing Pharmaceutical increased price of Daraprim (orphan drug) from $13 per pill to $750 Martin Shkreli, CEO Turing Pharmaceutical testifies before Congress (February, 2016) Cites Fifth Amendment, remains silent Tweets afterwards: "Hard to accept that these imbeciles represent the people in our government"

10 Election Year Commentary Bernie Sanders The Sanders plan holds the pharmaceutical industry accountable when they defraud the American people. Today, nearly every major pharmaceutical company has been convicted of either civil or criminal fraud for violations including off-label promotion, kickbacks, anti-monopoly practices, and Medicare fraud. Even though the Justice Department has won suits requiring companies to pay hundreds of millions of dollars in fines, the prescription drug companies simply treat those fines as the cost of doing business. "The pharmaceutical industry has become a health hazard for the American people," Sanders said in a statement. "The time is long overdue for Congress to listen to the needs of the American people and not the enormously-profitable pharmaceutical industry. CNN September 2015

11 Election Year Commentary Hillary Clinton: Crack down on rising prescription drug prices and hold drug companies accountable so they get ahead by investing in research, not jacking up costs. The drug prices plan also "would eliminate corporate write-offs for direct-to-consumer advertising" that "can include confusing, misleading or incomplete information or exaggerated claims if not regulated effectively, CNN September 2015

12 Donald Trump Trump Vows to Take On Powerful Drug Companies, Drive Down Prices Wall Street Journal February 4, 2016

13 Anti-Kickback Individual Prosecutions 2015 Dr. Michael J. Reinstein (February, 2015) pleaded guilty to receiving illegal kickbacks totaling nearly $600,000 from two pharmaceutical companies (IVAX and Teva) sentenced to 9 months in prison, 120 hours of community service, $4.3M in penalties NP Heather Alfonso (June, 2015) pleaded guilty to accepting $83,000 worth of kickbacks (Insys Therapeutics) Rita Luthra, MD (October, 2015) indicted on one count of violating the Anti-Kickback Statute. (Warner Chilcott) allegedly paid Luthra $23,500 to prescribe its osteoporosis drugs

14 What is the correct percentage of promotional events to monitor? 1. Environmental Factors Public Perception Congressional Pricing Inquiry Election Year Commentary AKS Individual Prosecutions via Speaker Fees 2. Internal Factors Volume of Speaker Programs; Size of Sales Force Speaker Programs In Office Venue Based» Avoid Appearance of Kickbacks Product Risk Assessment Factors Disease State Off Label Potential Price

15 Appropriate Sample Sizes Guidance via CIAs Negotiated Agreements No mathematical consistency Company CIA Date Speaker Programs Field Days Novartis 19-Nov Sanofi 2-Sep DSI 7-Jan Shire 5-Sep Endo 21-Feb J&J 31-Oct Par 4-Mar-13 10% 20 Amgen 19-Dec BI 22-Oct Abbott 11-Oct GSK 28-Jun

16 CIA Language Random Risk Based Judgmental

17 CIA Language Random A sampling method in which all members of a group (population or universe) have an equal and independent chance of being chosen. Risk-Based done or calculated according to how much risk is involved. Judgmental Selected an opinion or decision that is based on careful thought.

18 Speaker Programs: Appropriate Sample Size Determining Factors Volume of Speaker Programs relation to size of sales force Types of Programs In Office Venue Based Product Risk Assessment Factors Disease State Off Label Potential Price

19 Speaker Programs: Appropriate Sample Size 1. Speaker Selection Frequency of individual speakers Prior Monitoring Results 2. Sales Region Regional Sales Trends Monitoring Results by Region 3. Expense Minimization Proximity to Monitor Location Maximize Efficiencies of Travel Costs

20 Total Programs Completed and Scheduled thru December 31, 2015 Monitored Date Future Target Speaker Abraham Lincoln, MD Jul George Washington, MD Aug Gerald Ford, MD Jul Dwight Eisenhower, MD 19 X Andrew Jackson, MD Jul Harry Truman, MD Oct John Kennedy, MD Oct Franklin Pierce, MD Aug Zachary Taylor, MD Jul Woodrow Wilson, MD 15 X George H.W. Bush, MD 15 X William McKinley, MD Aug John Adams, MD 13 7-Sep Chester A. Arthur, MD 12 X Jimmy Carter, MD 12 X James Buchanan, MD 12 X James K. Polk, MD Jun Richard Nixon, MD Jul Martin Van Buren, MD 11 X Ronald Reagan, MD Jun William Taft, MD 11 9-Aug Andrew Johnson, MD 11 X Barack Obama, MD Jul Grover Cleveland, MD Jul Herbert Hoover, MD Jul Millard Fillmore, MD Aug Theodore Roosevelt, MD Jul Ulysses S. Grant, MD Sep

21 Geographic Distribution

22 Speaker Programs: Appropriate Sample Size Determining Factors Volume of Speaker Programs Types of Programs In Office Venue Based Appearance of Kickbacks Product Risk Assessment Factors Disease State Competitive Environment Off Label Potential Price

23 Category and drug Allergy Diphenhydramine Anesthesiology Propofol Dexamethasone, propofol Meperidine Cardiology Amiodarone Aspirin Atorvastatin, simvastatin Indomethacin Dermatology Azathioprine Biologic agents (eg, etanercept, infliximab, intravenous immunoglobulin, rituximab) Gastroenterology Erythromycin Omeprazole Hematology/oncology Alendronate Dabigatran Doxorubicin Furosemide (nebulized) Rituximab Infectious disease Linezolid Sulfamethoxazole-trimethoprim Nephrology Acetylcysteine Mayo Clin Proc Oct; 87(10): Examples of Common Off-label Uses of Drugs Off-label use(s) Chemotherapy-related emesis, insomnia16 Intracranial hypertension Postoperative nausea Postanesthetic shivering Supraventricular tachycardia16 Antithrombosis in atrial fibrillation, Kawaskai disease16 Extended-interval dosing for hyperlipidemia16 Pharmacologic closure of patent ductus arteriosus18 Atopic dermatitis, pemphigus; psoriasis19 Alopecia areata, atopic dermatitis, Behçet disease, dermatomyositis, hidradenitis suppurativa, pemphigoid, pityriasis, vasculitis20 Gastroparesis21 Reflux-related laryngitis16 Hypercalcemia of malignancy16 Venous thromboembolism prophylaxis after orthopedic surgery22 Refractory multiple myeloma16 Dyspnea16 Idiopathic thrombocytopenic purpura, Waldenström macroglobulinemia16 Infective endocarditis16 Sinusitis16 Prevention of contrast nephrotoxicity16

24 Albuterol Erythropoietin Neurology Atenolol, metoprolol, propranolol Isoflurane Donepezil Gabapentin Lidocaine Tricyclic antidepressants Obstetrics Magnesium sulfate Category and drug Volatile anesthetics (eg, enflurane, isoflurane, halothane) Pediatrics Mayo Clin Proc Oct; 87(10): Examples of Common Off-label Uses of Drugs Off-label use(s) Hyperkalemia16 Anemia of chronic disease16 Migraine prophylaxis10 Seizure, status epilepticus Frontotemporal dementia23 Bipolar disorder, diabetes, fibromyalgia, neuropathic pain symptoms, headache, hiccups, hot flashes, restless leg syndrome24 Postherpetic neuralgia24 Bulemia, insomnia, irritable bowel syndrome, neuropathic pain symptoms15,16,24 Premature labor16 Intraoperative uterine contraction Amoxicillin (high dose) Atenolol Intranasal desmopressin Pediatrics (continued) Morphine Sildenafil Pulmonary Volatile anesthetics (eg, enflurane, isoflurane, halothane) Psychiatry Atypical antipsychotics (eg, risperidone, olanzapine, quetiapine) β-blockers Citalopram Fluoxetine Trazodone Urology Sildenafil Otitis media in children16 Hypertension in children16 Nocturnal enuresis25 Pain in children11 Pulmonary hypertension in children16 Status asthmaticus26 Anxiety, dementia, eating disorders, obsessive-compulsive disorder, personality disorders, posttraumatic stress disorder, substance abuse27 Social phobia, public speaking28 Alcoholism, fibromyalgia, irritable bowel syndrome, obsessive-compulsive disorder, pathologic gambling, stuttering16 Borderline personality disorder, diabetic neuropathy, fibromyalgia, hot flashes, premature Insomnia in elderly patients16 Sexual dysfunction symptoms in women29

25 Prior Results Examples of Speaker Program Monitoring results requiring follow-up

26 Example (Anti-Kickback) Upon Monitor arrival 30 minutes prior to the program, the Sales Representative was not present. Attendees began to arrive and order drinks and appetizers prior to the Sales Representative arriving, which is against company policy. The Sales Representative eventually arrived 45 minutes late along with the Speaker. Upon arrival, the Speaker began a brief discussion on the disease state, however this discussion was extremely limited and there were no slides displayed or handouts provided to attendees. Further, the Speaker never provided an appropriate disclaimer as is outlined in the PHRMA Guidance.

27 Example (Off-Label) During the dosing schedule discussion, the Speaker suggested that starting doses of all drugs are FDA mandated and are typically not high enough. He recommended using the top dosage of drugs, for example stating that the Product X 25 mcg dose is worthless, I always use the 50, which is inconsistent with the product label. The product label states that certain patients should be initiated only on 25 mcg dose. The Speaker recommended to the audience I disagree with the company on this.

28 Example #3 (Fair Balance) The label specifically states that grapefruit and grapefruit juice should be avoided in patients taking Product A, since these may inhibit CYP3A4 and alter product concentrations. An attendee responded with a comment that he does not always follow this guidance; if my patient wants a half a grapefruit on a Sunday morning, I do not inhibit them. The Speaker agreed with this comment and recommended limiting grapefruit intake. However the Full Prescribing Information clearly states that grapefruit and grapefruit juice should be avoided in patients taking the product.

29 Sample Methodology Example Product A Programs Scheduled 100 Less: 15% Cancellation Rate 15 Estimated Programs 85 Percentage Monitoring Target 8.0% Number of Programs to Monitor 7 Tracking Cancellation Rates are important: Attaining your target sample % AKS appearance Sample % calculated based upon: Volume of Speaker Events Product Risk Assessment Up to Date Results of prior engagements

30 Field Day Selections Random Size of Sales Force Ongoing Investigations Hot Line Reports Results from other monitoring ( , FCRs) Sales Results Trends

31 Summary The OIG Guidance: strongly encourages pharmaceutical manufacturers to develop and implement and refine compliance elements that uniquely address the areas of potential problems, common concern, or high risk. Environment remains hostile Sample Selections require a logical and defensible methodology

32 Risk-Based Compliance Monitoring Sample Sizes and Selection Methodology March 17, 2016