Policy and Medicine

United Kingdom Office of Fair Trading: Accuses GlaxoSmithKline for Pay for Delay

In January of this year, we noted that the U.S. Supreme Court agreed to hear a case to decide whether agreements between brand-name pharmaceutical companies and generic makers to delay the entry of generic drugs to the market—so called “pay for delay” deals—violate antitrust laws.  “In a typical case, a generic rival challenges the patent of a brand-name competitor, which then pays the rival a sum of money to drop its challenge,” reported Reuters.  

A study by RBC Capital Markets Corp. of 371 cases during 2000-2009 found brand-name companies won 89 at trial compared to 82 won by generic drugmakers.  Another 175 ended in settlement deals, and 25 were dropped, reported TimesNews.net.

Oral arguments for the case—FTC v. Actavis—were heard in late March of this year, and there was significant coverage of the case by industry and various stakeholders.  A decision against the pharmaceutical industry would further shorten the patent protection period on many branded drugs.  Below is a summary of oral arguments and comments from various lawyers and stakeholders.

Forbes reported that while the Supreme Court case is considering the legality of such agreements, AstraZeneca entered into a new agreement with Actavis and its partner Egis Pharmaceuticals, to begin selling a generic copy of Crestor in May 2016, and Actavis will have to pay AstraZeneca a 39 percent royalty on net sales until the end of pediatric exclusivity in July 2016.

Pay-for-Delay Ban in the U.K.?

Interestingly, as pharmaceutical companies in the U.S. wait for the Supreme Court’s decision, regulators in the U.K. have now decided to stop pay-for-delay agreements as well—going after GlaxoSmithKline (GSK) of paying competitors to keep generics off the market, reported FiercePharma.

The drug is Seroxat--Paxil in the U.S.--and the agreement dates to 2001 through 2004, Reuters reports.  The accusation come from U.K.’s Office of Fair Trade (OFT) and accuses the U.K. drugmaker of making “substantial payments” to Alpharma Ltd., Generics and a unit of Teva Pharmaceutical Industries to keep their versions of the antidepressant off the market.

The OFT said it had a duty to investigate the case given the importance of generic medicines in keeping a lid on costs for the country's National Health Service (NHS).  “The introduction of generic medicines can lead to strong competition on price, which can drive savings for the NHS, to the benefit of patients and, ultimately, taxpayers,” said Ann Pope, senior director of services, infrastructure and public markets at the OFT.

GSK disputes the allegations, which relate to deals that were effective between 2001 and 2004.  GSK said it did nothing wrong and points out that European Commission regulators reviewed the old deal in 2005-2006 and decided not to act on it.  “GSK supports fair competition and we very strongly believe that we acted within the law,” David Daley, a spokesman for the London-based company, said by e-mail to Bloomberg, adding that the deals resulted in “generic versions of paroxetine entering the market before GSK's patents expired.”

The companies will have an opportunity to respond to the allegations before the OFT decides if competition law has been infringed.  If the U.K. does press on, GSK could be fined up to 10% of its £26.4 billion sales in 2012, reported Reuters.

AstraZeneca Plc, the U.K.’s second-biggest drugmaker, and Sanofi are also among companies the Brussels- based commission has queried as part of its probes into the companies’ tactics to keep copies of their medicines off the market, reported Bloomberg.  Johnson & Johnson and Novartis AG in January were also sent charge sheets by the EU over a pay-for-delay deal that may have hampered the sale of generic versions of pain killer fentanyl in the Netherlands. Drug developers use a variety of techniques to delay generics, the EU said in a 2009 report.

FTC v. Actavis

As noted by John Kamp, Executive Director of the Coalition for Healthcare Communication, “The biopharma industry seems to have the legal advantage.  The Federal Trade Commission (FTC) has struggled for over a decade just to get this case to the Supreme Court and has lost more challenges on the way than it has won.  The law supports settlements over litigation, even in antitrust cases.  Further, one Justice (Alito) recused himself, requiring the FTC to get five votes out of eight to prevail.” 

Kamp also pointed out that “The legal struggle is over three legal principles” and “Laws favor all three -- patent protection, settlements over litigation, and vigorous competition.”

FTC argued for the Court to start with a presumption that all pay-for-delay agreements are illegal, however, Justice Stephen G. Breyer called that test “rigid,” according to the Washington Post. 

MedPage Today noted that Deputy Solicitor General Malcolm Stewart explained that the Justice Department has since 2009 viewed such settlements as unlawful and that the drug companies should convince the court they're valid.  Justice Kennedy, however, said that the government’s test was the “same for a very strong patent as a very weak patent,” which the Justice said, “doesn’t make a lot of sense.”

MedPage noted that Justice Sonia Sotomayor questioned why it would be the responsibility of the drug companies to prove the settlement was lawful rather than the government to prove that to a court.  “It would seem to me that you have to bear the burden -- the burden of proving that the payment for services or the value given was too high,” Sotomayor told Stewart.  “I don’t know why it has to shift to the other side,” the article notes. 

Justice Antonin Scalia asserted that the Court shouldn’t “overturn understood antitrust laws just to patch up a mistake that Hatch-Waxman made.”  Similarly, Kamp pointed out that Justice Anthony Kennedy, often seen as the swing vote, “suggested that if Congress made a drafting mistake enabling these settlements in the Hatch-Waxman statute upon which the decision rests, it’s up to Congress, not the courts, to change the law.”  We previously noted that in March, Senators Charles Grassley (R-IA) and Amy Klobuchar (D-MN) introduced Senate bill 214 (S.214), A Bill to prohibit brand name drug companies from compensating generic drug companies to delay the entry of a generic drug into the market—also known as the Preserve Access to Affordable Generics Act.

In addition, Senators Al Franken (D-MN) David Vitter (R-LA), Dick Durbin (D-IL), Jeanne Shaheen (D-NH), and Bernie Sanders (I-VT) introduced S. 504, the “Fair and Immediate Release of Generic Drugs Act,” in mid-March, reported Patent Docs.  The bill is aimed at banning settlement agreements of ANDA litigation between innovator drug companies and generic drug manufacturers.  According to blog post author Kevin E. Noonan, “the bill contains provisions that preclude the 180-day exclusivity period granted to the first ANDA filer from any party that has entered into a ‘disqualifying agreement.’” 

“Another provision limits agreements on deferring commercial marketing, which are defined as being between a first ANDA filer and NDA holder (or owner of an Orange Book listed patent that was the subject of a Paragraph IV certification) and wherein the first filer agrees “not to seek an approval of its application that is made effective on the earliest possible date” or “not to begin the commercial marketing of its drug on the earliest possible date after receiving an approval of its application” or both” he writes.

The bill also contains a notice provision to the FDA that requires that the “text” of any agreement “that has been reduced to writing” (or a “written detailed description” of any agreement not reduced to writing) be submitted to the Secretary of HHS "not more than 10 business days after execution of the agreement.”

In response to industry’s arguments, Kamp noted that the FTC argued vigorously that the “pay for delay” drug patent settlements create extraordinary profits for the private companies, which harm consumers much more than in any other antitrust settlement situation.  While the decision may be too close to call, Kamp pointed out that “populist policy and politics favors drug cost savings, especially in the face of escalating healthcare costs and the need to control the growing deficit.  While the law seems to favor pharma, especially with the more conservative justices, the politics of less expensive drugs may be tougher, especially as the case moves to Congress.”  For example, the American Medical Association, AARP, and a group of states attorney general have come out in favor of banning these agreements.

However, Generic Pharmaceutical Association (GPhA) CEO Ralph Neas said that every patent settlement has brought a generic drug to market before the relevant patent ended, and that about two-thirds of the generic that were launched in 2010 and 2011 became available earlier than they would have otherwise due to a settlement, reported by Forbes.  Justice Kennedy suggested that brand-name drug companies should “not be allowed to pay generic-drug manufacturers more than those companies could expect to get by winning patent litigation,” notes the Washington Post.  In addition, Justice Elena Kagan sympathized with consumers, and noted that these agreements are merely “splitting monopoly profits, and the person who's going to be injured are all the consumers out there,” Justice Kagan said.

Physician Payment Sunshine Act: Opportunities and Challenges for Global Implementation

In a recent client alert from the law firm Debevoise & Plimptom, LLP, several attorneys discussed the potential international implications that can affect physicians and manufacturers in light of the finalized Physician Payment Sunshine Act regulations.   The authors noted that the Department of Justice (“DOJ”) and Securities and Exchange Commission (“SEC”) “have aggressively investigated and prosecuted life sciences companies under the FCPA for alleged misconduct and improprieties involving members of the medical profession.”

We previously noted FCPA cases involving Johnson & Johnson, Pfizer, and Eli Lilly.  Consequently, such companies “increasingly have begun monitoring relationships with physicians and medical practitioners overseas, who often qualify as ‘foreign officials’ under the FCPA.”  While the Sunshine Act is applicable only in the U.S., the regulations raise “questions as to whether and to what extent companies subject to U.S. regulations may opt to globalize their domestic transparency systems, whether in response to similar current or anticipated demands imposed by non-U.S. regulators or otherwise.”

The authors noted that the “Sunshine Act also has implications for multi-national organizations’ ex-U.S. operations” and “covered companies may want to consider implementing flexible transparency and spend-tracking systems on a global scale that simultaneously ensure compliance with U.S. law while taking into account similar policies and legislation in other countries.”  However, they recognize that choosing a single global system is not easy.

After giving a brief overview of the final regulations, the alert notes that while companies “finalize their data collection systems and make determinations about applicable policies and procedures to ensure compliance …. careful consideration should be given to recent FCPA investigations and the growing trend in transparency legislation worldwide.”  They note that “For some companies, it may be wise to implement some form of spendtracking and data collection systems globally, although adopting a single global practice will be challenging.”  Accordingly, the authors debate the benefits and risks of using a global transparency system.

Arguments in Support of Global Implementation

Given the increased FCPA scrutiny life science companies face, particularly for payments, gifts and other transfers of value to state-employed health care providers in foreign countries, the authors note that the Sunshine Act may actually “provide an opportunity to improve companies’ FCPA compliance.”  Specifically, implementing Sunshine Act compliant tracking procedures on a global scale may assist companies in monitoring their relationships with foreign medical professionals.  “Essentially functioning as an early warning system, a global spend-tracking system theoretically could help curtail, if not avoid, time-consuming investigations and expensive settlements that have become commonplace.”  For example, the alert notes

• In April 2011, J&J agreed to pay $70 million to the DOJ and SEC for alleged FCPA violations, including allegations that J&J subsidiaries “paid bribes to public doctors in Greece who selected J&J surgical implants, public doctors and hospital administrators in Poland who awarded contracts to J&J, and public doctors in Romania to prescribe J&J pharmaceutical products.”
• In December 2012, Eli Lilly & Co. agreed to pay $29 million in connection with allegations that its subsidiaries made improper payments “to foreign government officials to win millions of dollars of business in Russia, Brazil, China, and Poland.” In particular, the SEC alleged that “[e]mployees at Lilly’s subsidiary in China falsified expense reports in order to provide spa treatments, jewelry, and other improper gifts and cash payments to governmentemployed physicians.”
• A number of other life sciences companies are the subject of pending FCPA investigations.

“Worldwide spend-tracking and data collection systems could prove useful in monitoring relationships with state-employed health care practitioners, uncovering improper spending activities, and training personnel on how to remain within the limits of U.S. law,” the alert maintains.  Accordingly, “the global implementation of transparency systems would help to ensure compliance with the Sunshine Act while serving as a proactive tool for monitoring FCPA compliance.”

“Companies may also want to consider implementing spend-tracking systems on a worldwide scale given the growing trend in global transparency, as evidenced by recently adopted legislation and professional guidelines” and “some companies are already doing so.”  For example, France passed its own Sunshine Act in 2011 (inspired by the U.S. the authors write), which requires companies to develop transparency and disclosure protocols.  The law establishes two types of reporting rules:

(1) public declarations of interest by experts regarding any connection they may have with covered companies, and

(2) the disclosure of agreements between covered companies and recipients. With regard to the latter, information to be disclosed includes research and development contracts, grants, speaking arrangements, consulting contracts, grants, gifts, payments, and any other benefits.

Although the law’s implementing decree was expected in January 2013, it has not been published and thus the law is not yet enforceable. 

In addition, Slovakia passed several amendments in 2011 that subject health care companies to certain restrictions and requirements regarding their relationships with medical practitioners.  “Specifically, pharmaceutical companies are prohibited from financing, sponsoring, or supporting events geared toward health care professionals unless the purpose is solely educational or scientific.  In addition, companies must report all advertising and marketing expenses, as well as any direct or indirect non-monetary benefits provided to health care professionals. Lastly, health care professionals who are authorized to prescribe or dispense drugs are forbidden from accepting payments, gifts, or nonmonetary benefits from covered companies.”

The alert also points out foreign trade associations that have embraced the concept of self-regulation with respect to relationships between life sciences companies and medical practitioners.  “The European Federation of Pharmaceutical Industries and Associations (“EFPIA”) represents European national pharmaceutical industry associations.  The EFPIA Code of Practice on Relationships Between the Pharmaceutical Industry and Patient Organizations requires members to publish reports detailing any financial support (direct or indirect) provided to patient organizations, as well as any agreements existing between the parties.”

“The Association of the British Pharmaceutical Industry (“ABPI”) is a health care trade association with more than 180 members in the United Kingdom.  The group’s code of practice already requires members to disclose a wide variety of information regarding relationships with medical practitioners, including donations, gifts, grants, payments, sponsorships, and consultancy agreements. Industry organizations in Australia and the Netherlands have adopted similar measures requiring health care companies to publicly disclose financial relationships with medical professionals, while a professional association in Japan also requires that members implement specific transparency policies.”

“Although Sunshine Act-compliant record-keeping may not entirely satisfy transparency legislation or professional guidelines in other countries, global implementation could provide companies with a sound framework that could be tailored to meet the requirements of a particular regulatory system,” the alert acknowledges.  “Adopting a global spend-tracking system also would avoid the need to create transparency systems on a piecemeal basis as new laws and regulations are passed.”

Arguments Against Global Implementation

Given the uncertainty in the amount of costs associated with U.S. compliance with the Sunshine Act, the alert notes that “health care companies might be disinclined to expand Sunshine Act compliant reporting systems on a global scale.”  The authors recognize that companies must take a number of steps to comply with the Sunshine Act, including:

• Identifying products and devices that are covered by the statute,
• Defining payments and transfers of value subject to reporting,
• Assessing current relationships with health care professionals and teaching hospitals to determine which parties qualify as covered recipients.
• Developing and reexamining policies relating to transparency protocols and record retention.  
• Designing and developing adequate data collection systems and train relevant personnel (e.g., employees, third party contractors, and covered recipients).

While some companies have had a head start given provisions in their Corporate Integrity Agreements, “even those companies’ systems must be adjusted to conform with CMS’s recently issued rule.”

The authors recognize that “it is inevitable that complications will arise based on the sheer volume of information that must be compiled, processed, and submitted to CMS.”  Companies undoubtedly will encounter

• discrepancies among data sources that must be reconciled,
• complexities in determining how spend data should be identified and categorized, and
• challenges in deciding how to properly interpret the Sunshine Act’s reporting exceptions

“Companies also will have to ensure that they are adequately adhering to their reporting policies, a process that likely will require additional internal auditing and quality control mechanisms. In addition, the data must be validated and certified prior to submission, a process that likely will necessitate dedication of additional human and technological resources.”  

“Nor will the extensive data management efforts cease once the information has been reported. Companies must maintain all books, contracts, records, documents, and other evidence regarding payments, transfers of value, and ownership and investment interests for five years from the date that the information is published on CMS’s website.  CMS has acknowledged that some records will likely need to be retained for a longer period. Companies also will be subject to periodic government audits, evaluations, and inspections.”

As a result, the authors maintain that implementing a global Sunshine Act-compliant data collection systems is “unlikely” to “simplify any of these issues, especially given differences between U.S. law and foreign legislation and standards”; with  global requirements relating to spend tracking and data collection being “far from uniform.” 

“Although a handful of countries have enacted transparency laws, some are merely at the early stages of drafting legislation, others rely on self-regulation by professional associations, and many have yet to address the issue at all.  As a result, developing even the most basic global data collection system will involve some educated guesswork. Implementing policies on a global scale would thus increase the already uncertain costs of compliance, which could grow exponentially,” the authors write.

Conclusion

“Given the global trend toward transparency regulation, companies should at least consider whether expanding data collection and spend-tracking systems to their ex-U.S. operations would be a viable and beneficial option.  Adopting a thoughtful, holistic approach to the worldwide implementation of Sunshine Act-compliant systems could streamline the transparency process and assist companies in more easily satisfying emerging legislation and regulations, as well as facilitate companies’ efforts to monitor FCPA compliance.  It may be prudent, however, to first assess the full impact and cost of complying with the U.S. reporting requirements.”

Global Patient Groups Rank Pharmaceutical Companies

FiercePharma reported a recent survey done by PatientView, which measured the corporate reputation of pharma companies in Germany, Italy, the UK, and the U.S.  The survey, based on the opinions of 600 patient groups worldwide, showed that patients in Germany and Italy are much less cynical about the industry than U.S. patients. 

Almost two-thirds (63%) of patient groups in the U.S. opined that pharma’s reputation declined last year.  Only one-third of Italian groups had the same opinion, while 37% of German groups did.  U.K. patient organizations topped Germany by only three percentage points, with 40% seeing pharma's reputation on a negative trajectory. 

More than half of Italian respondents (52%) said pharma has a good--or even excellent--reputation, PatientView found, largely above the 34% worldwide. 

The Germans were less impressed; only 30% assessed pharma's rep as good or excellent.  While German groups give pharma high marks for making high-quality products, they weren't impressed with the industry's ethics. Only 14% see pharma's marketing practices as ethical, and only 14% say the industry acts with integrity.

Still, U.S. respondents were more critical. Only 4% figure pharma's reputation improved last year, compared with 21% worldwide. Less than half gave pharma good marks for patient safety.  And the industry even earned low marks for innovation, with only half of U.S. groups seeing the industry as innovative. 

Countries also ranked individual companies: Bayer came in first in the U.S., followed by a tie between AstraZeneca and Eli Lilly.  Janssen, a Johnson & Johnson subsidiary, ranked highest in Germany, with Abbott and Roche (in second and third). U.S.-based Pfizer topped out in Italy, with Novartis and Roche next.  Pfizer was also ranked number one in the U.K.  Here are the links to the main page plus each country’s report: 

-       Germany

-       Italy

-       U.K.

-       U.S.A.

Physician Payment Sunshine: Pharmaceutical Payments in the UK

The Association of the British Pharmaceutical Industry (ABPI) recently published aggregate totals of payments made last year to doctors, nurses and other healthcare professionals as part of a drive towards greater industry transparency, reported by PMLiVE.  Transparency became a requirement when ABPI members voted in 2011 to amend its Code of Practice to help increase transparency of working practices between pharma and healthcare professionals and increase trust.   

The obligation covers payments relating to the sponsorship of NHS staff to attend medical education events, training and speaker fees.  All companies will also publish the number of healthcare professionals who have received these payments. 

The report showed that Pharma companies in the UK paid healthcare professionals £40m in sponsorship and support during 2012.  The £40m figure is an estimate based on information received from, or published by, 35 out of the top 44 companies based on UK sales in 2012.  When such information is unavailable, the ABPI said it has taken the average spend for a company of similar size and added this to the total figures.  This compares to figures in the US, where big pharma was found to have paid US doctors $150m in the first eight months of 2011. 

ABPI’s CEO, Stephen Whitehead: “Full transparency about these relationships is right and appropriate and we have taken the lead to make this a reality.  “By publishing these figures industry's aim is to ensure these vital relationships are open and transparent.”  He also explained the need for pharma payments to healthcare professionals, saying it was “right” that they were reimbursed fairly for their time.  “These figures also show another way in which the pharmaceutical industry adds value to the NHS by supporting training and development and medical education,” he added. 

Interestingly, the report comes at a time when ten pharma companies have been
“found guilty of breaching the ABPI Code at a urology meeting in Ireland last year,” reported the PharmaTimes. 

The companies include: Pfizer, Orion, Ferring, Astellas, Baxter, Ipsen, Allergan, Takeda, Recordati and Janssen.   

“The complaint, brought by a group of NHS health professionals, criticised the companies who were all supporting the annual meeting organised by the Irish Society of Urology (ISU), which was held in Belfast in September 2012.  The complainants said that the first page of the scientific programme, which was handed out to NHS staff attending the event, featured photographs of the very luxurious, five-star venue and nearby attractions, which they felt placed “undue emphasis on non-scientific aspects” of the meeting.”   

The welcome message on the first page of programme also read: ‘The social aspect of this meeting is extremely important and the two evening events promise great enjoyment.  The unique opportunity to have our gala dinner in Stormont was one that we couldn’t pass over!’  Most of a second day of the meeting was dedicated to playing golf and leisure activities as clearly marked in the programme, the health professionals said. 

The complainants alleged that the pharma companies that supported this meeting seriously breached the Code on the grounds of “excessive hospitality”.  The PMCPA said that it considered that the scientific content was “not unreasonable”, adding that it had consisted of one and a half days of education.  Considering all circumstances, the PMCPA panel said it appeared that the pharma companies listed on the back page of the programme had supported all the arrangements for the two-day meeting held at a luxurious venue with golf and a gala dinner, and found that the impression this gave was “unacceptable”.

“The Panel also considered that purchasing a ticket for the gala dinner was inappropriate, saying the educational content of that day (which lasted for 3 hours 40 minutes in the morning) did not justify the gala dinner in the evening, which appeared to be a social event; high standards had not been met, and breaches of the Code were again ruled.  But the PMCPA stopped short of finding these firms guilty of bringing the pharma industry into disrepute, the most damaging breach available.”

 

The European Medicines Agency Mitigating Drug Shortages in Europe

The European Medicines Agency (EMA) recently released a proposal for how it can help mitigate potential and real drug shortages stemming from manufacturing problems, reported FiercePharmaManufacturing.  The six-page proposal notes that “Recent unexpected disruptions to the manufacturing supply chain due to manufacturing/GMP (good manufacturing practices) compliance problems have resulted in acute and chronic shortages of important medicinal products in the European Union (EU) requiring changes to prescribing information, and initiation of patient allocation programs.” 

The Reflection Paper is concerned with public health crises that arise due to unforeseen disruptions within the manufacturing process, caused by manufacturing/GMP compliance problems and affecting medicinal products for human use, independent of their route of authorisation, where a need for co-ordination of the assessment and risk reducing actions at a Community level has been identified. Supply disruptions not caused by manufacturing/GMP compliance problems fall outside the scope of this Reflection Paper. 

EU legislation currently requires mandatory pre-notification by Marketing Authorisation Holders (MAHs) of disruption of supply in the case of permanent or temporary cessations and for manufacturers of medicines in the case of any defect that could lead to an abnormal restriction in supply. 

It will be interesting to see if the Food and Drug Administration (FDA) and the EMA work together on this proposal, perhaps by entering into a Memorandum of Understanding (MoU).   

The regulators’ dilemma  

Over the past two to three years there have been a number of public health crises caused by acute and chronic supply shortages as a result of manufacturing/GMP compliance problems.  Experience obtained has been analysed by EMA and a number of lessons learned have been identified.   

In some cases defective medicines had to be left on the market to prevent shortages of life saving medicines as there is no available alternative and the risks linked to a possible exposure with the defective product are considered less than those linked to the unavailability of the product.  In some cases of GMP non-compliance the ability of Regulators to take action against a manufacturing site was restricted in order to avoid product shortages. Very difficult risk-benefit judgements had to be made between poor quality processes or product, or no product at all.  

The switching of patients to alternatives may also be hindered by factors other than supply per se and beyond the control of the Network.  For example, the exclusive link between peritoneal dialysis solutions from a certain MAH, the patient and the connector meant the exclusion of competitor products so that patients were inextricably linked to products from that MAH and could not be switched without undergoing a surgical procedure to change the connector further increasing the risk to patients.  

The impact of globalisation  

The globalisation of manufacture has continued to increase in importance so that many medicinal products have extended manufacture and supply chains, which increases the risk of supply disruption including new vulnerabilities.  Many sources of active substances for life-saving medicines, e.g. antibiotics, are now wholly located outside the EU, some located in countries that have uncertain political and regulatory systems and which may be prone to natural disaster.  The 2011 tsunami in Japan illustrated how natural disasters can impact the supply chain of pharmaceuticals.  

Manufacturing is in consolidation, leading to one or very few manufacturing sites supplying at a global level so failure at these sites leads to global supply shortages. There may be no redundancy or fail-safe capacity built into the global supply chain.  EMA has seen the case of a single contract manufacturer with particular capabilities may be depended upon for several key products.  With the arm’s length involvement of the MAH, contract manufacturing can be prone to marginal GMP compliance and consequent potential quality problems leading to supply problems.  

The industry’s approach  

EMA noted that “industry’s risk management tends to be very reactive rather than proactive.”  As a result, they called for “Sustained pressure” “to bring about a change in a manufacturer’s approach to quality risk management and supply chain security.” 

The current regulatory framework  

Unprecedented import of large quantities of unlicensed versions of medicines by Member States to prevent a shortage had to be supported by rapid and sustained pressure on MAHs to introduce variations to regularise the situation.  The need for urgent variations or better still pre-planned inclusion of failsafe manufacturing site capacity in marketing authorisations needs to be considered.  

Even if there are several potential suppliers at a global level, only one or two may have been included in a given marketing authorisation to the EU.  It, therefore, can be difficult to add these quickly in a time of crisis – all the more so in the case of biological medicinal products where there are greater regulatory hurdles as a result of concerns about the equivalence of product from different manufacturing sites.  

Collaboration and cooperation within the Network  

Actions at national level are taken to address local supply shortages without information being shared within the Network.  Proactive risk management and clear and transparent communication by the MAH are essential measures to maintain trust between all stakeholders.  International collaboration amongst Regulatory Authorities at a global level is vital to ensure better supervision of these globalised supply chains.  There may be a need to mobilise resources from outside the Network in order to assess problems and provide solutions.  

The interfaces between medicinal products and other products such as medical devices can be important and there is a need for further discussion about how best these interfaces can be managed.  The existence of monopolies in supply of medicines restricts options for risk mitigation.  There is a need for further discussion in order to address this issue.  

Envisaged activities  

While the causes of shortages are varied and complex, the challenge remains to effectively co-ordinate an assessment, to develop risk minimisation measures to alleviate the impact on patients, and to communicate within the Network, with international partners and with healthcare professionals, patients and the general public. On occasions, EMA is being asked to coordinate the follow-up to an emerging event in the absence of an appropriate legal framework.  

In some cases, the need for rapid implementation of risk minimisation measures is paramount.  Short and medium term measures will be undertaken to enhance the current approach.  In addition, there are some aspects which will require discussion with bodies outside the Network, e.g. in the area of medical devices. 

Short term actions  

Based on the findings and analysis noted above, EMA proposed ten (10) short term actions the agency will be taking to combat drug shortages 

1.    Establish an internal catalogue of Centrally Authorised Products (CAPs) and non-CAPs requiring coordination at EU level (e.g. referrals) that have experienced product shortages to facilitate future analysis of trends and communication on shortages.  

2.    Maintain a public catalogue of current shortages of CAPs and medicinal products where an EU co-ordination of assessment has been undertaken with links to all relevant Opinions, communications, etc. MAHs will be invited to report shortages caused by manufacturing/GMP compliance problems on a voluntary basis.

 3.    Develop a common understanding of the concept of “essential” medicine for subsequent application at national level and develop a decision tree to assist National Competent Authorities (NCAs) in deciding what shortages should be dealt with at EU level (also providing clarification on the most appropriate regulatory framework to be applied).  

4.    Provide clarification on how to best provide national input into the development of EU advice/ communication and how such EU advice/communication and national advice/communication can be complementary.  

5.    Establish and publish a Standard Operating Procedure (SOP) for handling reports of shortages in supply of medicinal products due to quality defects and manufacturing problems and where an EU co-ordination of assessment is necessary.  The procedure should outline the interlinking of regulatory, pharmacovigilance, GMP inspection, assessment and communication aspects of dealing with shortages due to unforeseen events in the manufacturing supply chain.  

6.    Revise through the GMDP IWG the Community Procedure “Procedure for Handling Rapid Alerts Arising From Quality Defects” to include transmission of alerts in the event of a shortage in supply of medicinal products due to quality defects and manufacturing problems, whilst ensuring that this will not result in non-urgent information being transmitted. Revise through the GMDP IWG Chapter 8 of the GMP Guide “Complaints and Product Recall” to clarify reporting requirements relating to restriction of supply in case this relates to a quality defect and a recall of batches.  

7.    Explore if “crisis” situations arising from shortages in supply of medicinal products due to quality defects and manufacturing problems can in the future also be addressed in the context of the EU Regulatory Network Incident Management Plan for medicines for human use. 

8.    Develop international co-operation in this area so that there is a sharing of information on specific shortages (with or without impact on other territories) and sharing of information on best practices on risk management and prevention strategies. 

9.    Raise the awareness of the impact of medicinal product shortages and stimulate industry reaction and improvements (whereby industry should propose solutions) in business continuity planning guaranteeing better access for patients to essential medicines by organising a public workshop between Regulatory Authorities, industry, patient and healthcare representatives to outline the problems encountered.  

10. Undertake a survey of past initiatives taken by NCAs to manage/prevent shortages in order to develop an inventory of possible tools available to NCAs and to share best practice.

Medium term actions 

EMA will:

1. Facilitate risk benefit evaluation where risk of shortage has to be balanced with potential risk due to presence of a product defect.
2. Promote better and proactive risk management by MAHs by requiring submission by all MAHs of a risk-analysis of their manufacturing process identifying any weaknesses and, depending on the severity, provide a contingency plan and proposals to strengthen the identified weaknesses.
3. Investigate processes that could be used to measure the impact of medicinal product shortage in patients experiencing its consequences, e.g. lowered dose or switch to an alternative product.

CME in Europe: CME Good Practice Group Core Principles

The Good CME Practice Group (composed of medical education companies in Europe) published its core principles to drive standards for CME in Europe (see full description below); these relate closely to the new UEMS criteria:  

1. Appropriate education is based on clear learning objectives derived from identification of performance gaps and unmet needs.
2. Balance needs to be evident in content, faculty and review, with content developed independently of sponsor.
3. All relevant information should be disclosed to the learner, including how the content has been developed and the terms of financial support.
4. Post-activity evaluation should measure satisfaction, knowledge uptake and intent to maintain or change behavior in line with learning objectives. 

Pharmaceutical and device companies are now subject to more rigorous guidelines for support of CME events in Europe.  These and other changes also affect managers of venues for these events, as was pointed out at the recent congress of the International Congress and Convention Association (ICCA), held in Puerto Rico.  Coupled with the new criteria for CME accreditation, the coming year promises to be a learning experience for industry and congress directors.  Why? 

The European Medical Technology Industry Association (Eucomed) has just implemented a mandatory assessment of all European conferences in which a Eucomed member is participating, to determine if the event is compliant with Eucomed's Code of Ethical Business Practices.  John McLoughlin, chairman of the independent compliance panel, told attendees at the ICCA congress that a company can be sanctioned if the conference fails to meet assessment criteria including:  

• The conference program must be focused on serious medical content targeted to attendees, have no gaps for recreation and be provided 90 days in advance for review.
• The location and venue must be accessible, conducive to a scientific session, not in a resort setting.
• Hospitality must be modest, not include entertainment, and include family or guests only at extra charge. 

Guidelines for pharma are similar in some respects, much more detailed -- but voluntary -- said Martin Jensen of Lundbeck, vice-president of the International Pharmaceutical Congress Advisory Association (IPCAA) at the ICCA meeting.  These went into effect early in 2012, and include:  

• Promote scientific education and networking in a compliant environment
• Ensure than congress-related activities create a value for patients
• Societies must disclose budgets in advance and provide an audit after the event
• 5-star resorts are unacceptable, even if unrated 

“The large European specialty congresses of today will shrink in size in the future,” Lew Miller of WMGS predicted.  “Cost and advanced technology will move these events to be distributed in a number of smaller locations, linked by streaming video with audience interaction.”  He also indicated that the trend toward performance evaluation of CME could change the nature of large didactic conferences. 

CME Core Principles 

CME in Europe is evolving rapidly with an increasing number of countries adopting voluntary or mandatory systems of CME participation for their physicians as evidence mounts that good CME programs improve clinical practice and outcomes.  The requirements of educational programs are also changing rapidly, particularly with a need for clear demonstration that a CME-accredited activity has been developed independently by a faculty, meets educational needs, is free from bias and is of high quality.  However, during this rapid evolution, it has become clear that there are misunderstandings and confusion amongst CME providers in relation to standard and regulations. 

To address this challenging situation, the Good CME Practice Group undertook an initiative to establish a set of standard core principles with a view to adoption by European CME providers and other key organizations involved in provision of CME programs.  The Good CME Practice Group consists of 12 European non-society education providers with shared objectives. 

The Group developed four core principles relating to (a) appropriate education, (b) effective education, (c) fair balance and (d) transparency.  In order to seek advice and input from peer groups and others involved in CME including accrediting bodies and medical societies, 93 representatives from these bodies were asked to complete a questionnaire and provide comments on the core principles.  To ensure the final guidelines developed would be of highest relevance to the audience, thus promoting the highest chance of adoption, the following provisions were incorporated:

 

• To liaise with key stakeholder groups in European CME at each stage of development of the core principles to ensure alignment with their regulatory, legal and operational expectations. These stakeholders comprise members of the CME accreditation bodies, medical societies and pharmaceutical company financial supporters.
• To validate the guidelines through a formal consultation process with the ultimate target audience (through the European and national medical societies) and the CME accreditation bodies themselves.
• Ensure that all recommendations are clear and practical in today’s CME environment

 

Consultation phase

 

Drafts of the core principles were tested during a consultation phase with key stakeholders in European CME.  The consultation involved participants from a range of organizations including national and European accreditation boards and medical societies across Europe.  Participants in the consultation process were asked to comment on each individual principle in terms of whether it would set an appropriate standard, whether implementation of the principle is feasible and whether application of the principle is likely to improve the quality of education.  Respondents were also asked to state (yes/no) whether they would endorse adoption of each principle by all parties involved in providing CME programs, including financial supporters, accrediting bodies, providers and faculty. 

 

Overall, there were significant levels of endorsement of the principles by all stakeholders with 95%, 90% and 92% recommending adoption of principles 1, 2 and 3, respectively by all involved in provision of CME programs.  A large majority (87%) also endorsed adoption of principle 4. Overall, responses were similar between types of organization.

 

Appropriate education

 

The Group adopted the following: CME providers should ensure that educational activities have clear learning objectives that are derived from a coherent and objective process that has identified performance gaps and unmet educational needs.  The education must be designed to positively reinforce existing good practice and effect a sustained change in daily clinical practice as appropriate.

 

This principle was particularly well received with 94% of respondents agreeing or strongly agreeing that it sets an appropriate standard.  A similar proportion (87%) agreed that the principle would lead to improved quality of education. Notably, 80% of respondents agreed or strongly agreed that implementation of the principle was feasible with 13% neither agreeing nor disagreeing.  It was noted that accreditation guidelines from the EACCME require details for educational activities on how a needs assessment was performed together with a demonstration of how educational objectives were derived from that assessment. This requirement, combined with the aim of the Good CME Practice Group to provide a set of guiding principles that would set the highest standard of best practice, persuaded the Steering Committee to keep reference to a gap analysis in the principle.  

 

Fair balance

 

The Group adopted the following: All relevant information should be disclosed to the learner so that they understand fully how the content has been developed and presented.  This includes the terms of the financial support, relevant disclosures of faculty and organizations involved in the development of the scientific content, and the presentation of the program. 

 

Response to this principle in relation to setting an appropriate standard stimulated a high level of endorsement of 90%. Similar high levels of agreement were achieved in relation to feasibility of implementation (90%) and likely impact on quality of education (93%).  Only 3% either disagreed or strongly disagreed with any statement regarding this principle.

 

A challenge to this principle was received in the consultation phase highlighting that financial support for educational programs is not exclusively the domain of pharmaceutical companies but could be a medical society, academic institution or similar. In this situation, it is likely to be appropriate for the supporter to be involved in program and content development.  The Steering Committee considered this feedback but felt that it is essential for the perception, credibility, integrity and success of CME program that content must be developed independently of all commercial organizations and their interests such that patient interests take precedence. 

 

Transparency

 

The Group adopted the following: Balance needs to be evident in content, faculty and review.  Content has to be developed independently of the sponsor and reflect the full clinical picture within the framework of the learning objectives. 

 

Approximately two-thirds of respondents strongly agreed that this principle sets an appropriate standard and a further 31% agreed with this point.  There was good agreement (82%) that this principle would lead to improved quality of education although 15% were undecided. Similarly, 79% agreed or strongly agreed that implementation of the principle was feasible.

 

Responses during the consultation phase and additional comments consistently reflected concerns about the feasibility of full transparency rather than its desirability. For example, more than one of the participating bodies suggested that the current system did not allow for sufficient transparency (for example, the tendency to show disclosures briefly on an opening slide) and that all organizations involved in an accredited activity should disclose their experience in educational programs. Based on these comments and the general feedback, the Steering Committee recommended that the drafted wording of the principle should be accepted.

 

Effectiveness

 

The Group adopted the following: Post-activity evaluation should measure satisfaction, knowledge uptake and intent to maintain or change behavior in line with learning objectives.  To facilitate implementation of the core principles and ensure consistency of approach, the Good CME practice group have developed a checklist to guide providers through the fundamental processes in effective CME

 

A number of comments were received for this principle. A consistent point was that while acknowledging that a measure of effectiveness was necessary, this can be ‘difficult to implement’ as not all users completed an evaluation form.  On reviewing the comments and data showing overall that there were doubts about the feasibility of implementation and likely impact on quality of education, the Steering Committee reworded the draft principle and removed the reference to the Moore scale.

 

Independence and transparency

 

At the time of inception of the Group, it was clear that there was a significant level of disquiet amongst most parties involved in provision of, and use of, CME in relation to

the quality and independence of programs. To a large extent, this reflects concerns around bias of programs due to industry support. But research from Germany and the US has indicated that industry-funded CME programs are statistically equivalent to non-commercially supported CME activities in the degree of detectable bias present14,15, underscoring the point that there are numerous potential sources of bias, that include intellectual and professional as well as financial biases. This point was recently acknowledged by the European Society of Cardiology in their CME policy document, which concluded that financial sources of bias must be acknowledged by full disclosure16. It is worth noting, nevertheless, that the relationship of perceived bias to actual bias is poorly understood as the difficulty of measuring actual bias has led to a paucity of studies in this area15,17.

Core principles around ‘fair balance’ and ‘transparency’ were developed to address the challenges of potential and perceived bias in educational activities and were most robustly supported and endorsed by those in the consultation phase.  A key component of the ‘balance’ principle is that ‘content must be developed independently of the

sponsor’.  Although this may be a self-evident means to avoid bias or undue influence, some accrediting bodies in Europe (particularly at national level) still allow significant input into content by the commercial supporter.

 

The Good CME Practice Group maintained that this should change and, where there is a lack of clarity in the regulations, this should be rectified by further discussion and engagement with the appropriate accrediting bodies. Moreover, the authors recommend that there is increased monitoring of programs and sanctions applied where necessary.  While most people and organizations involved providing CME strive to produce high quality, objective and unbiased programs, ultimately, the user/learner should be in a position to assess this for themselves.  They can only make informed decisions, however, if they are in full possession of information relating to potential conflicts of interest.  

 

Scientific and medical journals have tended to be at the forefront of requiring comprehensive declarations of potential conflicts of interest and have defined conflicts of interest in relation to authors and financial supporters of publications.  In a similar manner, both faculty and providers of CME-accredited programs should provide full disclosures of any personal conflicts of interest in addition to a clear declaration of source and terms of funding with details of their relationship, if any, with the funding organization. Learners should always be given the opportunity to report bias (perceived or real) through evaluation and feedback forms (provided at the point of learning).

 

While making learners aware of potential conflicts of interest is fundamental, it is also the responsibility of parties involved in the development of the content to address such conflicts as early as possible in the programme development.  It is essential that content is evidence-based medicine (with only appropriate levels of evidence included), a balanced view of any therapeutic approach is presented and that any guidance given reflects consensus opinion from the medical community. All stakeholders involved in content development or presentation must agree and align with these concepts at the initial stages of the activity.  If for any reason any party feels unable to do this, then consideration should be given to asking them to withdraw.

 

Appropriate and effective education

 

The goal of CME (and CPD) is to improve patient care through improved clinical performance of healthcare professionals translating into improved clinical outcomes. Evidence indicates that a major contributor to achieving this goal is a formal assessment of educational needs of the target audience.  A requirement for a needs assessment is embodied in the first core principle of appropriate education and should give rise to learning objectives for the activity.  The authors felt that it was important to crystallize the need to reiterate that course content encompasses current best practice and standard of care at this point.

 

There has been extensive debate over many years as to the how to measure educational outcomes and assess the effectiveness of CME and yet, the results of an extensive and systematic literature search reveal few publications on this subject. Undoubtedly, in many cases, assessment of some CME activities is more a measure of participation than learning or assessment of knowledge gain through correct completion of multiple choice questions (that are not always robustly designed). Ideally, since the goal of CME is to improve clinical care and patient outcomes, this should be the primary outcome measurement.

 

Haynes et al., reported a systematic analysis of 248 original articles relating to evaluation of CME.  While 38% of studies measured change in clinical performance, only 7% of studies assessed the impact on patient outcomes.  The authors note the challenge of measuring changes in patient outcome when this can be affected by many factors including patient-related delays in seeking medical care etc.  This is particularly pertinent to this analysis since the studies reviewed were conducted predominantly in primary care.

 

A subsequent analysis of the literature relating to CME found that only 50/777 were randomised controlled trials that measured physician performance and/or health outcomes.  Findings of this study highlighted the complexity of developing CME programs that can improve patient outcomes noting that enabling interventions were more effective that predisposing interventions. It was also noted that there was a lack of a robust association between change in physician performance and patient outcome.

 

This lack of clear relationship is likely to be due at least in part to confounding factors such as non-adherence to medications or even by therapy area (e.g., hypertension) where improvements are difficult to measure as there is often relatively good control and management.  A recent study is more robust and has been able to show an association between learning programs in primary care and decreased mortality due to coronary heart disease3. This prospective, randomized, controlled trial assessed the effect of repeated case-based education of primary care practitioners on mortality. The interventions centred on regularly updating and distributing guidelines for lipid-lowering management combined with attendance at 1–2 case seminars/year over a 2-year period.  At the end of the study period, mortality in the intervention group was 22% compared to 44% in the control group.

 

However, it remains difficult to get true measures of effective learning outside of a healthcare system for a number of reasons. Principal amongst these is the difficulty and expense of trying to measure change in behaviour or patient outcomes. Performance improvement CME has attempted to address measurement of change in clinical behaviour with a step in the assessment that assesses the user after an interval of time.

 

However this presents some challenges in terms of ensuring physician participation in the follow up particularly when there is no incentive for them to do. This is evident from the recent report from the Accreditation Council for Continuing Medical Education (ACCME) in the US26, showing that in 2011 only 0.75% of the total CME accredited programs (by number of hours) were classed as Performance Improvement CME.

 

A further challenge to measuring effective learning beyond the immediate MCQ assessment is that expectations of changing behaviour can be unrealistic when discussed in the context of a single event or 1-hour online course. Extensive consideration was given, therefore, to the final principle as regards how much guidance should be provided in terms of measurement of outcome. It was thought that at this time, that not only is it difficult to measure change in patient care but the Group felt that a physician’s manager or peer group were best placed to review a physician’s progress following CME activities.  The Group would recommend that participation in, and learning from, such CME activities become a component of the formal review system in all countries. The first draft of the principle included reference to the Moore scale as an objective measure of successful learning

 

However, in the consultation process, this proved to be the most contentious principle with comment that this was not feasible for many and that there was a trend towards assessment of level of satisfaction as an adequate/ realistic measure. The Steering Committee felt, however, that while it would remove reference to the Moore scale, it was important to recommend that, in addition to assessment of user satisfaction and knowledge uptake, a measure of intention to maintain or change behaviour was essential and should be included as such in all evaluations. Further research on novel, practical and affordable ways to assess change in practice may help to identify reasonable methods for achieving more meaningful evaluations and driving improvements in education standards. 

Conclusion 

In summary, the overall goal of the Good CME Practice group is to provide guidance on how European CME providers can contribute to improving clinical care. The group aims to do this by championing best practice in CME, maintaining and improving standards, mentoring and educating and working in collaboration with critical stakeholders.  By this means, CME programs should be better targeted to address true educational needs of learners.  Moreover, improved design of initiatives will lead to effective education that translates to positive changes in the clinical practice of users. 

Key to success of this is to ensure that the core principles developed in this initiative relating to (a) appropriate education, (b) effective education, (c) fair balance and (d) transparency are recognised and implemented by all involved in the CME arena along with continued research efforts in the impact of these principles on practice.

European Council for Continuing Medical Education: The Accreditation of Live Educational Events

Effective January 2013, all providers seeking accreditation of their live continuing medical education (CME) programs from the European Accreditation Council for CME (EACCME) will have to abide by new requirements set by its parent organization, the European Union of Medical Specialists (UEMS) at its October meeting in Cyprus.  The new criteria parallel those of the US accreditation system and the recommendations of the Good CME Practice Group, an initiative of the European CME Forum. 

The European Union of Medical Specialists (UEMS) was founded in 1958 with the aim of representing the interests of specialist doctors at an international level. The UEMS is a non-governmental voluntary organization comprising the national medical organizations that represent medical specialists in the European Union and in associated countries. With a current membership of 34 countries, and 39 specialist sections, the UEMS provides for the representation of approximately 1.4 million medical specialists working in Europe. 

In announcing the new criteria for live educational events (LEE), Edwin Borman, MB ChB, secretary general of the UEMS, said: “The requirements for Europe are being strengthened, and now move providers to do more, e.g., appropriate needs assessment, targeted educational objectives and some measure of outcomes, as well as full financial disclosure.”  Here are some key clauses:  

• The provider must structure the LEE to fulfill defined educational needs for a defined target audience
• The provider must identify and communicate expected educational impact in a doctor’s practice, and provide for feedback on the extent to which objectives were met
• The LEE must include methods to promote active learning, including opportunities for audience participation
• The provider must ensure that all faculty and members of the Scientific and/or Organizing Committee disclose potential or actual conflicts of interest and that actual conflicts have been resolved
• The source of all funding for the LEE must be declared and available to learners;
• Content must be free of any sponsor influence and of any form of advertising or bias 

The Accreditation of Live Educational Events by the EACCME® 

The UEMS established the European Accreditation Council for Continuing Medical Education (EACCME®), in January 2000, with the aim of encouraging high standards in the development, delivery and harmonization of continuing medical education (CME). This was to be achieved through the international accreditation of CME events, and the establishment of a system for the international acceptance of CME credit points. After just over a decade of function, the UEMS-EACCME® (henceforth EACCME®) accredits around 1400 applications per year for meetings providing international CME. In 2009, the EACCME® introduced a system that provides for the accreditation of e-learning materials.  

In its policy paper, from 2001, the Basel Declaration on Continuing Professional Development (CPD), the UEMS defined CPD as “the educative means of updating, developing and enhancing how doctors apply the knowledge, skills and attitudes required in their working lives”. The UEMS remains committed to this concept that encompasses educating medical specialists for the wider responsibilities required for specialist medical practice.  

The UEMS acknowledged the need for CME credits as a simple means of confirming involvement in CME/CPD, hence has introduced a common “CME currency”: the European CME Credit (ECMEC). While the EACCME® provides a credit-based accreditation system, the UEMS draws attention to its policy, stated in the Basel declaration, that doctors should employ a range of educational methods and not rely solely on formally accredited CME for their continuing education.  The UEMS has agreements based on the mutual recognition of credit points with the American Medical Association – for live educational events and for e-learning materials – and with the Royal College of Physicians and Surgeons of Canada – for live educational events only.

 

Accordingly, the EACCME® described the criteria and mechanisms for its accreditation of Live Educational Events (LEEs).  This accreditation will apply for all European countries and specialities that have a recognition agreement with the EACCME®, and for countries providing CME/CPD events that will be attended by doctors who reside in Europe. The paper states what criteria will be applied for the accreditation of LEEs, and describes how the Provider of CME/ CPD (henceforth referred to as “Provider” – see appendix 6) should apply for EACCME® accreditation.

 

The UEMS defines live educational events as meetings, the primary purpose of which is the provision of educational material of a medical nature to doctors, with the aim that they will achieve educational benefit. It is expected that, as a result of this educational process, patients also will benefit from the lessons, applied in practice, that their specialist doctors have learned.  The UEMS recognises that some educational activities employ a range of methodologies, hence straddle areas of definition. The EACCME® will consider the accreditation of such activities on the basis of: the primary form of presentation; or the potential for the learner to engage, actively, with the educational event or material.

 

The UEMS draws attention to differences in national recognition arrangements for CME/CPD credits obtained from attending LEEs, and emphasises that doctors must refer to these when providing a record of their CME/CPD activities.  The newly published document represents the updated criteria that will be applied by the EACCME® when considering applications for the accreditation of LEEs, as of 1st January 2013. This document supersedes all previous documents related to such accreditation, originally UEMS D9908 and subsequent revisions.  This document will apply until reviewed, in no later than three years’ time.

 

Educational Objectives and Fulfillment of Learning Needs

 

The Provider must structure the LEE to fulfill defined educational needs.  The application must demonstrate that a “needs assessment” process has been completed, how that process was performed, and what relevant educational needs have been identified from that process.

 

The Provider must define the “target audience” for whom the LEE is most likely to be suitable.  This must be explained in terms of the specialties and seniority of doctor(s) most likely to benefit (henceforth referred to as the “Learner(s)”).

 

The Provider must identify and communicate the expected educational outcome(s) of the LEE.  These must be explained in terms of the expected educational impact in knowledge, skills, attitudes or behaviors, or ethical lessons, and where in a doctor’s practice this will have an impact.

 

Description of the Live Educational Event

 

The Provider must provide the title of the LEE, its venue, date(s), and a clear description of the nature of the event.  This must indicate whether the LEE will involve lectures, discussions, workshops and/or other educational methods, single or multiple sessions, and whether these will be sequential or in parallel.  The EACCME® will consider applications for whole meetings, or, where these fulfill minimum time-based criteria, for specific components of a meeting. Separate applications for accreditation will be required for academic satellite symposia that are not part of the conference program.

 

The LEE must be presented in a manner suitable for an international audience.  The LEE will need to demonstrate that it can accommodate the educational needs of an international audience with the primary language determined by the composition of the audience and facilities available for interpretation as required. International terminology for procedures and therapeutic agents must be used.

 

The LEE must include methods to promote active learning.  The application should state how this will be achieved. Examples include: multimedia presentations; protected time for question and answer sessions; opportunities for audience participation; key-pad votes and discussion.

 

The Provider must provide detailed information on the duration of the LEE.  This is particularly important in order that the EACCME® can determine the maximum number of ECMECs that may be claimed by a Learner who has attended the LEE. This must be a minimum of one educational hour, with each hour of educational time expected to count as one ECMEC, up to a maximum of 3 ECMECs for a half day and 6 ECMECs for a full day. The educational time can be structured flexibly throughout the day.

 

The Provider must indicate the mechanism(s) by which it will be verified that the Learner has engaged with the LEE in order to fulfill the educational objective(s).  As a minimum this must involve a mechanism for confirmation of attendance at the LEE.  The UEMS encourages the use of more sophisticated methods, such as smart cards confirming attendance at specific sessions, requiring the Learner(s) to complete questions based on the LEE material, requiring the Learner(s) to complete feedback forms, etc.  An online evaluation system linked with the provision of a CME certificate also will be acceptable.

 

The LEE must be conducted in compliance with all relevant ethical, medico-legal, regulatory, industry-based and legal requirements.  For example, this should include: confirmation of confidentiality for patients and other participants, or consent to inclusion of non-identifiable details within LEE presentations, compliance with research ethics requirements, compliance with data-protection legislation, and copyright arrangements. It is essential to ensure that patients are not, and cannot be identified in any of the materials presented. The relevant legal, regulatory and industry-based standards will be those for the country in which the LEE is being held.

 

Details of the Provider

 

The Provider must provide a short description of the Provider organization(s).  The Provider must submit a short description of their own organization, and any other(s) with which they are working with regard to this specific LEE, specifying, in each case, the organization’s contribution to the LEE. Where the Provider is a CME company producing a program on behalf of another organization (e.g. pharmaceutical or device manufacturer) their relationship must be fully disclosed.

 

The Provider must state the names and job titles of the individual(s) responsible for preparing the LEE.  The name and contact address of the person/organization primarily responsible for the delivery of the LEE must be provided. In addition, if these are from different organizations, the names and contact addresses must be provided of the persons/organizations responsible for the planning of the LEE, the administration of the LEE, the scientific program content of the LEE, and for billing purposes.

 

The Provider must provide the name, title and contact details of a medical practitioner who will take responsibility for the application for accreditation of the LEE. This doctor must be registered with a Medical Regulatory Authority, and his/her registration details must be provided.  Normally this will be a senior member of the Organizing Committee for the LEE. In all circumstances, this doctor will be expected by the UEMS to have verified the information submitted on behalf of the Provider in the application for accreditation.

 

The Scientific and/or Organizing Committee

 

The Provider must provide the name(s), job title(s) and contact details of the head, and all other members of the Scientific and/or Organizing Committee.  The person responsible for, or in charge of the committee responsible for, the planning of the scientific content of the LEE must be clearly identified.

 

The Provider must ensure that all members of the Scientific and/or Organizing Committee provide written declarations of potential or actual conflicts of interest.  All declarations of potential or actual conflicts of interest, whether due to a financial or other relationship, must be provided to the EACCME® upon submission of the application. Declarations also must be made readily available, either in printed form, with the program of the LEE, or on the website of the organizer of the LEE. Declarations must include whether any fee, honorarium or arrangement for re-imbursement of expenses in relation to the LEE has been provided.

 

The Provider must confirm that any actual conflicts of interest have been resolved .

Where there has been an actual conflict of interest involving a member of the Scientific and/or Organizing Committee, the EACCME® must be informed of how this has been resolved. The EACCME® considers it a responsibility of the head of the Scientific and/or Organizing Committee to ensure that actual conflicts of interest are addressed.

 

 

The Scientific and/or Organizing Committee must ensure that the LEE will provide a program that presents a scientifically balanced perspective of the subjects included.

This must include impartiality in the scheduling of subjects, lecturers and opportunity for discussion. Challenge through peer-review by participants during discussion sessions within the LEE can provide an effective safeguard.

 

The Faculty

 

The Provider must ensure that all members of the Faculty provide written declarations of potential or actual conflicts of interest.  These declarations must be made publicly available, either in printed form, with the program of the LEE, or, in electronic form, on the website of the organizer of the LEE. The EACCME® considers it a responsibility of the head of the Scientific and/or Organizing Committee to ensure that actual conflicts of interest are resolved. The EACCME® has provided a template, available on the EACCME® website, that provides a guide as to what information must be declared. These declarations must be retained for at least one year after the event for potential review by the EACCME®.

 

The Program

 

The Provider must provide the latest version of the program of the LEE at the time of application.  The information provided must include the required details of Faculty members and the titles of lectures, etc. that they will be delivering, and the expected learning outcomes. Details regarding the duration of individual lectures, workshops and sessions must be included, making clear the planned number of educational hours per day. The EACCME® will not permit major changes to the program following confirmation of accreditation.  Following the LEE, the Provider must also send the final version of the program to the EACCME® highlighting any differences from the version submitted with the original application for accreditation.  

 

Funding of the LEE

 

The EACCME® will only consider for accreditation LEEs that fulfill specific requirements related to their funding. Accordingly, events provided by the pharmaceutical and medical equipment industries will not be considered for accreditation.

 

The source(s) of all funding for the LEE must be declared, and be made available to Learners in a readily accessible manner.  Failure by a Provider to disclose the means of funding of a LEE will lead to rejection of its application. The Provider must provide documentation confirming the basis of the funding for the LEE, whether this is by sponsorship, educational grant, or any other means. While all sources of funding must be declared, the actual amounts provided need not be.

 

The Scientific and/or Organizing Committee must confirm that it has determined the content of all aspects of the LEE to be free of any attempt by sponsors to influence the Committee’s decisions.  All funding must be provided free of any attempt to influence the program, individual sessions, subjects for discussion, content or choice of Faculty members.

 

The Provider must submit information regarding the expected total number of Learners attending the LEE and the schedule of fees for these Learners.  The EACCME® recognises that, prior to the LEE, only provisional figures can be provided. The final figures must be included in the feedback report of the event that must be submitted to the EACCME® following completion of the LEE. Grossly or significantly inaccurate attendance declarations will lead to automatic rejection of an application and/or future applications.                                   

Promotional material  

All educational material must be free of any form of advertising and any form of bias. 

The EACCME® will reject any application that, in its opinion, includes advertising of any product or company directly related to any educational material.  The EACCME defines “bias” as “a tendency or preference towards a particular perspective, ideology or result, especially when the tendency interferes with the ability to be impartial, unprejudiced or objective.”  “Bias may be scientific, political, economic and financial, religious, gender-related, ethnic, racial, cultural or geographical.  Bias may occur in relation to a particular industry or commercial product such as a mechanical device or pharmaceutical agent, or in relation to a particular intellectual, political or other view, in situations where a range of products or views may be equally useful or valid.” 

Specific examples that will lead to automatic rejection of an application include: the use of a sponsor’s name in the title of the scientific program, a scientific session or a scientific lecture; the display of brand names and/or individual company logos in scientific lectures or in the scientific program. The EACCME® will accept a single page acknowledgement, in the scientific program, where all sponsors are recognized for their support of the LEE and programs that include the names of satellite symposia only if they are clearly identified as industry sponsored. All advertising components (including the listing of exhibitors) must be clearly separated and distinguished from the scientific/educational components of the program and identified as such.  

Where there is a valid evidence base for a specific therapy or agent, this may be stated, but this must be referenced in a manner that is appropriate for a scientific journal.  

The Provider must confirm that it will comply with the applicable national rules, regulations and industry standards regarding exhibition areas where companies are permitted to present their products.  

Review by Learners  

The Provider must provide a reliable and effective means for the Learners to provide feedback on the LEE, including the extent to which the educational objectives of the LEE were met. The Provider must commit to make available to the EACCME® a report on this feedback and on the Provider’s responses to this.  

These reports, and the responses to them by the Provider, will inform the EACCME® of the Provider’s track record for future applications for accreditation. The EACCME® will make available, as examples of good practice, suitable feedback forms.  

The EACCME® reserves the right to request doctors, who will be attending the LEE, to provide independent reports on the fulfillment of the criteria set out in this policy. 

The EACCME® will reject any application that, in its opinion, includes advertising of any product or company directly related to any educational material.  

Application 

The EACCME describes in this document the process for how CME providers can apply to have their program accredited.

Special Thanks to Lew Miller at Wentz-Miller for alerting us of these new requirements.

Clinical Care Options Launches In Practice HIV CME in South Africa

Clinical Care Options (CCO) recently announced it is developing a new program to support South African physicians and nurses in the management of HIV-infected and HIV/TB-coinfected patients. This new interactive digital training and certification program called inPractice® Africa will also provide training for HIV nurses.   

CCO is a leader in the development of innovative technology, print, and live medical education programs that reach clinicians in 200 countries around the world.  Known for its innovative programs and proprietary technology, the company creates original continuing medical education (CME) and information resources designed specifically for healthcare providers in the areas of HIV, hepatology, and hematology/oncology.  

The program is made possible by a unique Public Private Partnership Grant from USAID and grants from Abbott (ABT), Gilead (GILD), Janssen (JNJ) and Merck (MRK) pharmaceutical companies.  Importantly, inPractice® Africa will be developed in cooperation with two leading South African organizations involved in HIV/AIDS medical education: the University of the Witwatersrand (Wits) and the Foundation for Professional Development (FPD). 

The mission of inPractice® Africa is to reach HIV-treating physicians, nurses, and other healthcare professionals in resource-constrained settings and provide relevant, practical training and certification that can improve patient outcomes.  Leveraging CCO's existing inPractice® technology as a base, the program will add new mobile and offline capabilities to accommodate use in areas of Africa with limited or no internet access. The program's content will also be specifically designed with the support of an African faculty to meet the particular challenges in HIV care experienced across the continent.  

“This public-private partnership fits well with PEPFAR's efforts to increase the number of healthcare professionals, improve their retention in Africa and support task shifting to nurses and other healthcare workers,” said Charles Holmes, MD, Chief Medical Officer of PEPFAR.  “We are looking forward to seeing firsthand how this model that includes innovative technology and African curricula can contribute to HIV education, training, and support clinicians in a variety of practice settings.”  

The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) is the U.S. Government initiative to help save the lives of those suffering from HIV/AIDS around the world.  This historic commitment is the largest by any nation to combat a single disease internationally, and PEPFAR investments also help alleviate suffering from other diseases across the global health spectrum. PEPFAR is driven by a shared responsibility among donor and partner nations and others to make smart investments to save lives. 

CCO has been creating innovative HIV educational programs for more than 20 years. These programs have been used in more than 200 countries to improve the quality of care and health outcomes in HIV-infected individuals. 

“Over the last year, we've been on the ground in South Africa, Senegal, and Ethiopia, listening to stakeholders and providers, keen to understand the challenges of managing HIV care on the African continent. The content of inPractice Africa will be a direct reflection of what many providers shared with us, that is, the need for information customized to address common clinical challenges and support task shifting in this setting,” said Jeffrey L. Drezner, MD, PhD, inPractice's Managing Director. “inPractice® Africa underscores our ongoing commitment to improving global patient care across the spectrum of healthcare.” 

The inPractice® clinical decision support tool is already used worldwide and incorporates resources addressing HIV, hematology/oncology, and viral hepatitis. The product serves to translate and distill the constant stream of new research findings into practical knowledge that can be applied in the clinical setting. 

“We are excited to support the development and implementation of this pilot to provide a much needed educational technology platform that focuses specifically on both the African digital landscape and the sociocultural aspects of providing care for the men, women and children of Africa,” said Gustaaf Wolvaardt, MD, Executive Director of the Foundation for Professional Development (FPD).  He added: “We are committed to ensuring participation and utilization of this invaluable resource by clinicians across the country.” 

inPractice® Africa will be available in several forms including online, mobile (for smartphones and tablet computers that are gaining in use among healthcare providers in South Africa), and a version for PCs without an Internet connection. The program will provide structured educational modules that are certified for South African continuing professional development credits with integrated, easy-to-search reference content that facilitates decision making at the point of care. The program will also include access to health information databases specific to South Africa, including practice guidelines and drug reference information.

 

International: Supervised Off Label Marketing in France

Over the past several years, we have written numerous times about legal settlements involving pharmaceutical companies who were charged with the off-label promotion of drugs.  The Food and Drug Administration (FDA) approves drugs for specific intended uses, which are then placed on the labeling of the drug for physicians.  Doctors, however, can prescribe these FDA approved drugs for uses not approved by FDA, or off-label uses. 

The catch-22 is that manufacturers of such drugs are prohibited from marketing their drugs to healthcare professionals or these off-label uses, even though many of them are commonly used, and in some cases such as oncology, the standard of care.  Consequently, a recent scandal in France involving the drug Mediator has “paved the way for major changes in [France’s] regulatory system, including new measures aimed at strongly regulating access to drugs during their postmarketing ‘real life.’” 

Mediator (benfluorex) — a fenfluramine derivative approved for treating diabetes but prescribed for indications (weight loss) not included in the “summary of product characteristics” (label), caused sometimes-fatal valvular heart disease.  For regulatory agencies who approve such drugs, there is a delicate need to balance “rapid access to drugs for new indications against the limited information on their benefit–risk ratio for those uses.”   

A recently passed French law aimed at strengthening the safety of medicines and health care products (Law number 2011-2012, December 29, 2011) and a related decree regarding “Temporary Recommendations for Use” (TRUs; Decree number 2012-743, May 9, 2012) fill part of the gap, providing France with a regulatory process for temporarily supervising the prescribing of drugs for indications for which they are not yet licensed, according to a recent article in the New England Journal of Medicine. 

Marketing authorization for drugs is granted on the basis of their safety for specific indications, as ensured by a positive benefit–risk ratio in clinical studies.  To be appropriate and safe, a drug's use should adhere to its summary of product characteristics.  

The authors recognized, however, that “some licensed medicines may be prescribed for indications outside their marketing authorization in order to treat health problems for which there are currently no other approved medications — for instance, in the case of rare diseases or specific subgroups of patients.”  In addition, they noted that “Some off-label prescribing should be permitted to allow physicians to take good care of patients and offer them some therapeutic options, but such prescriptions must remain the exception to the rule and should be scrutinized and controlled by regulatory agencies using well-defined frameworks.” 

“The intention of the French law and the TRU decree is to open a relatively long observation window in order to assess the benefits and risks of a marketed drug for an unlicensed indication and to collect scientific information to ensure its safe use,” the article explained.  A TRU is granted for a maximum of 3 years, a window that should permit the manufacturer to expand its marketing authorization through the usual procedures.  

In addition, “the law gives pharmaceutical firms the responsibility for controlling off-label prescribing: they must monitor prescriptions’ adherence to marketing authorizations and must not market their drugs for unlicensed indications. If unconventional prescribing is observed, pharmaceutical firms must immediately inform the National Agency of Medicine and Health Product Safety (Agence Nationale de Sécurité du Médicament et des Produits de Santé [ANSM]) and take all appropriate measures to inform health care professionals and prevent off-label use.” 

“A TRU decision is issued a single time for any given drug and may result in a right to reimbursement for the drug for the designated indication. The ANSM will authorize a TRU if there are no other appropriate medications available. The ANSM may be alerted to the possible need for a TRU by the Ministry of Health, the institution in charge of Social Security Insurance, the High Health Authority, the National Cancer Institute, the reference centers for rare diseases, or patient advocacy groups.  After the agency assesses the data provided by the manufacturer and from academic scientific studies, it can issue a TRU.” 

A formal contract may be signed between the company marketing the drug and the ANSM.  Such an agreement would define  

• the patient follow-up,
• the efficacy and safety information to be collected,
• the real conditions of use, and
• the schedule for reporting data to the ANSM.  

“The cost of this follow-up must be covered by the pharmaceutical firms, but the follow-up itself can be delegated to specialized organizations or reference centers. This monitoring does not cover other off-label use not included in the TRU.  If there is found to be a risk to public health or a lack of follow-up of patients, the ANSM can modify, suspend, or withdraw the TRU.” 

The authors noted that several factors must be considered and carefully balanced by an expert committee before a TRU can be issued. 

1. The quality of the scientific evidence
2. The drug's safety.
3. The prognosis associated with a given disease
4. Frequency of the disease’s occurrence.  

If only anecdotal evidence or poor-quality studies exist, “further clinical trials will have to be conducted so that stronger scientific evidence may be gathered before a TRU can be obtained.”  In addition, it will be safe to issue a  TRU for a well-known drug with few side effects “than for a drug with serious side effects that has been on the market for only a short time.”  The authors noted that risks associated with other drug interactions and potential harm in specific populations (e.g., pregnant women, elderly, etc) should also be considered.   

The authors also noted that TRU’s should be issued for a more severe disease than a trivial one because patients and caregivers are more willing to accept greater uncertainty regarding the benefit-risk assessment for life-threatening disease with no alternatives (e.g., oncology and hematology, or infections diseases).  Finally, the authors expressed concern that a TRU could “hasten the conduct of clinical research” for rare diseases; something they wish to avoid since randomized trials remain the gold standard for drug development and approval.  However, they recognized the difficulty of performing such large trials for rare diseases.  

The authors asserted that “The regulatory rules for off-label use warrant strengthening not only in France, but also in the European Union and other countries, to reduce the potential harm to patients.”  They noted that the new French legislation also aims to  

• Facilitate and promote the development of new indications,
• Refine benefit–risk assessments for real-life prescribing practices, and
• Avert the loss of therapeutic options for eligible patients.  

“The advantage of TRUs is that they will encourage the development of possibly viable uses for marketed drugs and the monitoring of benefit–risk ratios for new indications. The potential downside is that once a new use has been temporarily authorized, it may be difficult to stop physicians from prescribing the drug for that indication even if new market authorization is not granted.”

US Foreign Corrupt Practices Act Pfizer Settlement: Future Implications and Recommendations

Pfizer Inc. (Pfizer) recently announced the resolution of a previously disclosed investigation by the United States government into its relationships with healthcare providers (HCPs) and government officials outside of the U.S.  To resolve alleged criminal violations of the U.S. Foreign Corrupt Practices Act (FCPA), Pfizer subsidiary Pfizer H.C.P. Corporation (Pfizer H.C.P.) entered into a two-year Deferred Prosecution Agreement (DPA) with the U.S. Department of Justice (DOJ) and agreed to the filing of a two-count Information charging the company with bribery and conspiracy to violate the FCPA. As part of the agreed-upon criminal settlement, Pfizer H.C.P. admitted the facts of the Information as true, and paid a fine of $15 million.  

A recent client alert from the law firm Arnold & Porter, LLP gave an in-depth analysis of the case, future implications, and recommendations for companies moving forward to avoid such penalties and misconduct.  

This case is a reminder that “U.S.-based multi-national medical products companies must have meaningful compliance programs that extend to their foreign subsidiaries and partners.”  Nevertheless, Pfizer’s settlement provides a “useful guidance to companies in the life sciences sector, as well as other global companies, for the implementation and maintenance of global anti-corruption compliance programs that prevent, detect, and respond to potentially improper interactions with government officials outside of the United States.” 

Last year, Johnson & Johnson paid $70 million to resolve improper payments by J&J subsidiaries to government officials in Greece, Poland and Romania in violation of the FCPA. 

Pfizer and its Wyeth LLC subsidiary also settled allegations by the U.S. Securities and Exchange Commission (SEC) that both companies made corrupt payments and violated the books and records and internal controls provisions of the FCPA.  Neither company admitted nor denied the allegations and each consented to the entry of a final judgment order enjoining each from future violations of the FCPA as a condition of the settlement. As a condition of the Consent Order, Pfizer has also agreed to provide the SEC with a written report describing its FCPA and anti-corruption remediation efforts after 180 days, and to provide two follow-up reviews documenting its monitoring efforts.  

Finally, apart from agreeing to pay $15 million in criminal fines, Pfizer has also agreed to pay more than $23.6 million in disgorgement of profits, including pre-judgment interest, while Wyeth LLC has separately agreed to pay $18.8 million.  

The alert explains that Pfizer’s case is instructive as to what kinds of activities can give rise to alleged FCPA violations.  Pfizer settled allegations (which it neither admitted nor denied) by the SEC that its subsidiaries (including Wyeth LLC) had made corrupt payments in Italy, China, the Czech Republic, Saudi Arabia, Indonesia, and Pakistan.  Arnold & Porter pointed out that while the Pfizer case was resolved in the U.S., “regulators in the United Kingdom, Germany, Italy, and other jurisdictions are scrutinizing industry relationships under their local anti-bribery laws, and therefore the concept of a global anti-corruption compliance program is not unique to only U.S.-regulated companies.”  

Timely and Meaningful Remediation Measures 

This case underscores the “value of early detection, prevention, and correction of alleged unlawful activity.”  Pfizer’s Corporate Compliance Division learned of potentially improper payments made by the Croatia office of Pfizer H.C.P. and made a voluntary disclosure of these payments to the SEC and DOJ in October 2004—neither agency had been previously aware of these payments.  “Pfizer then used internal and external Legal, Compliance, and Corporate Audit personnel to voluntarily undertake an extensive global review of its operations to analyze its relationships with government officials and government doctors in Pfizer H.C.P. markets and those of other subsidiaries.”  

“This review included specific assessments of the results of internal investigations that had uncovered evidence of potentially improper payments. Pfizer disclosed the results of the internal review to the government” and launched “extensive remedial actions, including: 

• Implementing enhanced anti-corruption policies and procedures,
• Developing global systems to support employee compliance with those policies and procedures,
• Adding FCPA-specific reviews to its internal audits,
• Performing proactive anti-corruption compliance reviews in approximately ten markets annually, and
• Conducting extensive anti-corruption training throughout the organization.   

Pfizer regularly reported to DOJ and the SEC on these activities and sought the government’s input concerning their scope and focus.”  As a result: 

• The government agreed to resolve the matter “without a criminal plea;”
• “DOJ assessed a 34% reduction off the bottom of the Sentencing Guidelines’ recommended fine range for FCPA violations;” and 
• The DPA terms do not require Pfizer to hire a corporate monitor to oversee its compliance with the terms of the DPA in recognition of the extensive enhancements Pfizer made to its global compliance program 

Continuing Scrutiny of Physician-Industry Relationships 

Arnold & Porter noted that this settlement is “another example of government authorities continuing to take the view that HCPs who are employed by government-run healthcare systems or make purchasing decisions within those systems (e.g., hospital formularies) are “foreign officials” within the purview of the FCPA.”  The FCPA defines foreign officials, in part, as “any officer or employee of a foreign government or any department, agency, or instrumentality thereof.” See 15 U.S.C. § 78dd-2(h)(2)(A); see also Pfizer H.C.P. DPA, (“In those countries with national healthcare systems, hospitals, clinics, and pharmacies were generally agencies or instrumentalities of foreign governments, and, thus, many of the healthcare professionals employed by these agencies and instrumentalities were foreign officials within the meaning of the FCPA.”). 

Over the past few years, industry has expressed its concern with this definition and asked the government to clarify the scope of this term.  Nevertheless, companies “must recognize that their global compliance programs must continue to monitor relationships between their employees and HCPs, regardless of how the foreign official definition may ultimately be construed.”  Specifically, “it is necessary to implement effective compliance controls on all interactions with HCPs outside of the United States, regardless of whether or not HCPs may be determined to be foreign officials under the FCPA.” 

This is particularly true in light of the Physician Payment Sunshine Act and the French Healthcare Payment Transparency Act, which will track and trace almost all payments from industry to physicians, and will be powerful tools for federal and state prosecutors to use in healthcare fraud cases, including those abroad.   

Conference travel and hospitality.  “Regulators worldwide require that global companies that choose to provide travel and hospitality only do so for legitimate purposes and monitor both the substance of the programs as well as the financial records documenting associated payments to ensure compliance with applicable laws. While an important part of both customer education and healthcare delivery, such provision of travel for HCPs to medical congresses or product training sessions can be subverted for corrupt purposes if effective controls are not put in place at the local market level, with appropriate global programmatic oversight.”  Manufacturers should follow the various industry codes, particularly the international ones.  

Here, the government alleged that Pfizer H.C.P. maintained an incentive program for its sales representatives (reps) in Bulgaria, whereby successful sales reps could invite their customers along on recreational trips to locations such as Greece.  According to DOJ, these customers included “government doctors” and internal documents indicated that the intent behind the program was to increase product sales by influencing purchasing and prescribing decisions of government doctors.  Pfizer also admitted that its subsidiaries in various Central and Eastern European jurisdictions had used expense-paid medical conference travel as an incentive to influence purchasing and prescribing decisions of government doctors.  

Product marketing and distribution clearances.  While many pharmaceutical and medical device companies now have special policies and procedures in place to govern employee relationships with members of government ministries and other regulatory bodies, the Pfizer case reflects the risks posed by private practice customers who also have regulatory responsibilities.   

For example, in Croatia, Pfizer H.C.P. entered into a consulting agreement in 1997 with one such “dual-role” customer—a prominent Croatian doctor and professor of internal medicine at a government-funded university.   According to DOJ, the Croatian doctor also had “influence over decisions concerning the registration and reimbursement of Pfizer products marketed and sold in the country” and at various times was involved with government committees that made marketing registration and clearance decisions in Croatia. 

Formulary decision-making responsibilities or work with quasi-governmental clinical guidelines committees. Between 2003 and 2005, Pfizer Russia, Pharmacia Croatia, and Pfizer H.C.P. Croatia employees allegedly used travel, hospitality, and bonus payments to influence formulary placement decisions.  In another instance in 2004, a Pfizer Russia employee requested a “sponsorship” for a local department of health employee who was assisting the chief pharmacologist of a regional pediatric hospital to compile algorithms for antibiotic therapy. In an internal document, the employee noted that “in return for this” the department of health employee and the chief pharmacologist would include Pfizer products in the algorithms which constituted a list of official government-recommended treatments. 

Due diligence, including anti-corruption reviews, of distributors in high-corruption-risk markets.  According to DOJ, Pfizer H.C.P. Kazakhstan entered into an exclusive distribution agreement with a Kazakh company that was valued at a minimum of $500,000.  According to DOJ, all or part of the value of the agreement was intended to be shared with Kazakh government officials.  In 2003, a regional supervisor at the Pfizer subsidiary sent a memorandum to his supervisor explaining that the controller of the Kazakh company was very close to government officials and that the company in question had likely been responsible for past problems in getting product approvals.  

Discounting arrangements with government hospitals and other institutions. While they serve an important business and healthcare delivery need (and are often required by the government-run entity subject to its tender rules), such arrangements can present compliance risks, particularly in high-corruption risk markets.  According to DOJ, Pfizer Russia maintained a “Hospital Program” which appeared to be a legitimate indirect price discounting program for Russian government hospitals. However, Pfizer admitted that Pfizer Russia had used the program to corruptly reward past purchases and prescriptions of Pfizer products, and to corruptly influence future purchases and prescriptions by HCPs employed by the hospital. Similarly, in Croatia, Pfizer admitted that its subsidiaries had created discounting arrangements with hospitals which included “bonus” terms whereby sales reps would share a percentage of product sales and provide travel and other items of value to senior doctors at public hospitals. 

Government Expectations for Industry Anti-Bribery Compliance Programs 

Arnold & Porter noted that Pfizer’s DPA appears to contain the most specific requirements of any pharmaceutical FCPA settlement and is quickly becoming synonymous with “enhanced compliance obligations” that set the standard for effective compliance programs.  The Pfizer H.C.P. DPA contains a four-part Attachment C which is tailored to Pfizer’s business and the facts giving rise to the settlement. Attachment C.1 sets out DOJ’s expectations for an effective compliance program, which includes:  

Requiring Pfizer to maintain mechanisms for preventing, detecting, and correcting potential FCPA bribery and books and records violations, such as written policies and procedures, executive oversight, training, due diligence procedures, contractual certifications, periodic testing and other general requirements.  

Attachment C.3 sets out Corporate Compliance Reporting requirements, according to which Pfizer agreed to provide status reports to DOJ on the implementation of its compliance program at least once every nine months.  Pfizer promises to report any credible evidence of questionable or corrupt payments, or credible evidence that relates to a violation of the books and records provisions of the FCPA. These reports will be provided through periodic, scheduled communications between Pfizer and DOJ.  Pfizer also agreed to perform three reviews and reports, detailing the anti-corruption remedial efforts performed and proposing improvements to its anti-corruption policies and procedures.  

The most detailed part of the Pfizer DPA is contained in Attachment C.2, which describes the compliance measures that Pfizer promises that it has taken or will take for the duration of the approximately two-year term of the DPA.  These obligations fall into six categories: (1) general; (2) complaints, reports, and compliance issues; (3) risk assessments and proactive reviews; (4) acquisitions; (5) relationships with third parties; and (6) training.  In addition to common requirements to address risk areas, DOJ has required Pfizer to maintain controls over gifts, speaker fees, travel, honoraria, donations, and other areas which are more specific to the medical products industry.  

For example, in addition to its anti-bribery policies, DOJ expects Pfizer to maintain its “Global Policy on Interactions with Healthcare Professionals.”  Given that legitimate HCP education, consulting, promotional speaking, and advisory relationships are an important part of the global pharmaceutical and medical device business, the recognition of industry-specific policies and procedures is important.  The Alert noted that “certain requirements appear to synthesize existing Pfizer policies, best practices from voluntary pharmaceutical association codes (such those adopted by the International Federation of Pharmaceutical Manufacturers and Associations), and concepts typically seen in domestic pharmaceutical settlements with DOJ and other authorities.”   

Pfizer has agreed to maintain procedures to limit the provision of items of value—gifts, hospitality, travel, grants, donations, consulting fees, speaker fees, honoraria—to government officials.  Similarly, Pfizer has promised to maintain policies and procedures that require all gifts or hospitality for government officials to be reasonable in nature and given only to relevant officials. 

Arnold & Porter also noted that Attachment C.2 provides a roadmap for how Pfizer is expected to monitor compliance with the written standards and structural elements it has agreed to maintain. “This section of Attachment C.2 is an important source of information for industry legal and compliance personnel as they formulate and implement their company-specific compliance work plans, particularly for high-corruption risk markets.” Attachment C.2 requires Pfizer to:  

• Continue its program of identifying five high-risk markets for annual FCPA proactive reviews. These reviews will include, among other things, on-site visits by an FCPA review team and review of a representative sample of contracts involving high-risk transactions.
• Continue to implement FCPA trend analysis, tracking and reviewing certain categories of interactions with foreign government officials and due diligence performed on third parties.
• Perform due diligence on acquisition targets, applying anti-corruption policies and procedures to acquired businesses.
• Perform risk-based due diligence on third parties before engaging the third parties, and update the due diligence at least once every three years.
• Perform due diligence on third parties that includes reviewing the third parties’ qualifications, analyzing the rationale for engagements, and identifying relevant FCPA risk areas.
• Require that trained members of the compliance or legal divisions review red flags raised during third party due diligence.
• Train directors, officers, executives, and those employees whose positions require performance of activities covered by Pfizer’s FCPA policies once every two years.
• Provide enhanced FCPA training to internal audit, financial, compliance, and legal personnel.
• Train relevant third parties at least once every three years, when appropriate.  

Conclusion  

Ultimately, Arnold & Porter recommended that multi-national life sciences company should become familiar with the facts of the Pfizer settlement “and take note of the benefits of maintaining a robust compliance program as a defensive measure in the event of a government investigation.”  The alert maintained that “the strength of Pfizer’s pre-existing compliance program, combined with timely self-reporting of potential violations, and aggressive and extensive remediation efforts were key factors in the government’s decision not to pursue a criminal plea, maximize fines and damages, or impose monitoring requirements.” Nevertheless, companies “must monitor employee-HCP relationships, particularly where they involve provision of travel and hospitality, or interactions with ‘dual role’ government officials.”