by K M Gopakumar
Millions of dollars given by major pharmaceutical companies to the World Health Organization (WHO) raise questions of compliance with the organization’s guidelines on interactions with commercial enterprises.
Currently, WHO’s relations with commercial enterprises are guided by the “Guidelines on interaction with commercial enterprises to achieve health outcomes” (http://apps.who.int/iris/bitstream/10665/78660/1/ee20.pdf?ua=1). The 107th Session of the Executive Board in 2001 “noted” the Guidelines that cover cash donations, contributions in kind, seconded personnel, collaboration for product development, collaboration for meetings etc.ÂÂ Compliance with the Guidelines has essentially been left to the Secretariat.
According to paragraph 11 of the Guidelines, “Commercial enterprises working with WHO will be expected to conform to WHO public health policies in the areas of food safety, chemical safety, ethical promotion of medicinal drug products, tobacco control, and others”.
It is notable that the draft Framework of Engagement with Non-State Actors (FENSA) currently being finalised by WHO Member States does not contain a provision that requires a commercial enterprise to conform to WHO’s polices, norms and standard. In the absence of such a clear provision FENSA could legitimise engagement with the private sector, which does not follow WHO’s policies in the areas of food safety, chemical safety, ethical promotion of medicinal drug products, tobacco control, and others.
WHO Member States at the resumed session of the Open Ended Intergovernmental Meeting (OEIGM) on FENSA is expected to look at the regulation of WHO’s engagement with the private sector. The session will take place on 7 to 9 December at the WHO headquarters in Geneva.
The experience with the implementation of the Guidelines on interaction with commercial enterprises to achieve health outcomes would be useful for the consideration of Member States.
In 2014, WHO received USD 6,158,153 from GlaxoSmithKline (GSK). It received USD 5,785,000 and USD 8,266,284 in 2012 and 2013 respectively from GSK. GSK Biologics paid USD 17,000.ÂÂ Novartis AG donated USD 5,300,000 in 2014 and USD 4,500,000 in 2013.ÂÂ Hoffmann-La Roche donated USD 6,158,153 in 2014 and USD 4,806,492 in 2013.ÂÂ The purposes of those donations were not disclosed.
However, the programme and budget portal provides the details of donations in 2015 during which GSK donated USD 4,094,000. Out of this 51.1% was for epidemic prone and pandemic prone diseases, 36.8% for neglected tropical diseases, 4.6% for alert and response capacities, 3.4% for strategic communications, access to medicine and health technologies and strengthening regulatory capacity, 0.7% for vaccine-preventable diseases, 0.2% for tuberculosis and 0.2 % for malaria.
In 2015 Novartis donated USD 2,834,000 of which 55.8% was for neglected tropical diseases, 34. 1% epidemic prone and pandemic prone diseases, 3.8% for alert and response capacities, 2.8 % for strategic communications, access to medicine and health technologies and strengthening regulatory capacity, 0.6% for vaccine-preventable diseases, 0.1% for tuberculosis and 0.1 % for malaria.
In 2015 Roche donated 2165000. Out of this 78.5% was for epidemic prone and pandemic prone diseases, 8.1% for alert and response capacities, 6% for strategic communications, access to medicine and health technologies and strengthening regulatory capacity, 1.2% for vaccine-preventable diseases, 0.3% for tuberculosis and 0.3% for malaria.
In 2015 Eli Lilly Company Foundation donated USD 1,218,000 to WHO for its tuberculosis program. (Source: http://extranet.who.int/programmebudget/Biennium2014/Contributor)
All the four companies earmarked their donations for specific areas set out in the agreements with the WHO Secretariat.
These donations raise prima facie concerns about the violation of provisions of the Guidelines which state that commercial enterprises working with WHO are expected to conform to various WHO policies including the ethical promotion of medicinal drug products.
As a general rule the Guidelines recognise that the WHO’s activities affect commercial enterprises. It states: “In establishing such relationships it should be borne in mind that WHO’s activities affect the commercial sector in broader ways, through for example, its public health guidance, its recommendations on regulatory standards, or other work that might influence product costs, market demand, or profitability of specific goods and services”.ÂÂ
Illustrations of WHO’s activities are provided: “Such activities include setting of norms for quality, safety, and efficacy of pharmaceuticals and related promotional practices; dissemination of information on pharmaceuticals; provision of guidelines for diagnostics and treatment or advice that might affect the market for individual products and product categories; establishment of chemical safety standards; and formulation of nutritional guidelines”.
The Guidelines thus put an obligation on the part of the commercial enterprises to comply with WHO’s policies in paragraph 11 cited above.
However, there are doubts about the actual implementation of the provisions of the Guidelines in light of the financial resources received from certain pharmaceutical companies such as GSK, Novartis, Hoffmann-La Roche and Eli Lilly. All the four companies have either been found guilty of, or investigated for, unethical promotion of medicines including suppression of safety data in different WHO Member States.
In 2012 GSK pleaded guilty and paid USD 3 billion on a charge of unlawful promotion of medicines. The press release of the United States Justice Department stated: “Global health care giant GlaxoSmithKline LLC (GSK) agreed to plead guilty and to pay $3 billion to resolve its criminal and civil liability arising from the company’s unlawful promotion of certain prescription drugs, its failure to report certain safety data, and its civil liability for alleged false price reporting practices, …” (http://www.justice.gov/opa/pr/glaxosmithkline-plead-guilty-and-pay-3-billion-resolve-fraud-allegations-and-failure-report). GSK was charged for promoting an anti-depressant medicine for persons under the age of 18, “even though the FDA has never approved it for paediatric use.”
Further, in 2014 China imposed a fine of USD 490 million on GSK for bribing doctors and top executives were sentenced to prison. However, imprisonment was suspended (http://www.bbc.com/news/business-29274822).
In 2014 Poland initiated a criminal investigation against GSK, again for bribing doctors. According to a BBC report, a former sales representative for GSK in the Polish region of Lodz, Jarek Wisniewski, said: “There is a simple equation. We pay doctors, they give us prescriptions. We don't pay doctors; we don't see prescriptions for our drugs. We cannot go to doctors and say to them, 'I need 20 more prescriptions'. So we prepare an agreement for them to give a talk to patients, we pay ฃ100, but we expect more than 100 prescriptions for this drug” (http://www.bbc.com/news/business-26970873).
In 2014 the Italian competition authority (AGCM) fined both Novartis and Hoffmann-La Roche USD 251 million for entering into an agreement to prevent the sale of Roche’s cancer medicine Avastin to treat an eye disease, in favour of Novartis more expensive Lucentis that is jointly marketed by the two companies (http://www.bloomberg.com/news/articles/2014-03-05/italy-fines-novartis-roche-251-million-over-eye-drug).
According to a Reuters report dated 10 April 2014 the French competition authority also initiated a similar investigation against Novartis and Roche. (http://www.reuters.com/article/roche-novartis-search-idUSL6N0N21LG20140410#XsgWACcRuLhtzoXf.97)
In 2014 Italian authorities raided two Novartis facilities for alleged fraud committed against the Italian health ministry by inflating the price of a component of a flu vaccine (http://blogs.wsj.com/pharmalot/2014/06/20/novartis-offices-are-raided-by-italian-authorities-over-vaccine-pricing/).
In 2015 Japan took action against Novartis for the failure of reporting nearly 3200 adverse events (http://www.thelocal.ch/20150227/japan-orders-novartis-unit-to-suspend-operations). According to a website report, “Last year, prosecutors in Japan laid formal charges against Novartis in an ongoing investigation about the manipulation of clinical data, centering on studies of the company's blood pressure treatment Diovan (valsartan) which were alleged to have been tampered with to make the drug look more effective than competitors on the market.ÂÂ Meanwhile, the company has also come under scrutiny amid claims that its staff acted inappropriately in data collection activities relating to its leukaemia drug Tasigna (nilotinib), a probe that resulted in three senior management figures resigning from the Japanese unit including former head Yoshiyasu Ninomiya” (http://www.pmlive.com/pharma_news/novartis_japanese_subsidiary_threatened_with_suspension_640076).
In 2014 the European Medicine Agency concluded an investigation against Roche for suppression of drug safety reporting and forwarded the investigation report to the European Commission for further action. According to Reuters, Roche could face fines for failing to comply with so-called "pharmacovigilance" obligations under European Union rules, of up to 5 percent of its annual EU turnover, which totalled 12.8 billion Swiss francs ($14.6 billion) in 2011”. (http://www.reuters.com/article/us-roche-hldg-europe-idUSBREA3D15A20140414#jtPqeehqprGC77FE.97)
Similarly in 2014 a US jury ordered Takeda and Eli Lilly to pay USD 9 billion as punitive damage for suppression of drug safety data regarding the cancer risks on their diabetic drug pioglitazone.
The above mentioned cases are clearly in violation of WHO’s “Ethical criteria for medicinal drug promotion” (WHA Resolution 41.17 adopted in 1988: http://apps.who.int/medicinedocs/documents/whozip08e/whozip08e.pdf).
Paragraph 8 of the criteria reads: “Promotion in the form of financial or material benefits should not be offered to or sought by health care practitioners to influence them in in the prescription of drugs”.ÂÂ GSK executives were found guilty of bribing doctors China.ÂÂ
Paragraph 7 states: “All promotion-making claims concerning medicinal drugs should be reliable, accurate, truthful, informative, balanced, up-to-date, capable of substantiation and in good taste. They should not contain misleading or unverifiable statements or omissions likely to induce medically unjustifiable drug use or give rise to undue risks”.
Paragraph 19 states: “Medical representatives should not offer inducements to prescribers and dispensers”. The cases in Poland and China involving GSK are clear examples.
Paragraph 27 states: “Substantiated information on hazards associated with medicinal drugs should be reported to the appropriate national health authority as a priority, and should be disseminated internationally as soon as possible”. For instance, the action by Japan against Novartis, and the European Medicine Agency investigation against Roche for suppression of data.
Thus the above financial contributions to WHO would be in conflict with WHO’s criteria for ethical promotion of medicines and accordingly the Guidelines.
Further, when taking a decision to receive financial contributions the Guidelines (paragraph 12) require the WHO Secretariat to take the following steps: “In addition, evaluation criteria should be applied which are similar to those already in use by a range of public agencies in assessing potential partnerships with commercial enterprises, including: the public image, and financial stability and integrity of the company”.ÂÂ However, there is no clarity with regard to assessment of ‘public image’.
The donations mentioned above from GSK and Novartis could fall within a category of risk that has been identified in the draft FENSA document under negotiation, i.e. “whitewashing of a non-State actor’s image through an engagement with WHO.”
(In the draft FENSA document, paragraph 8 states: “WHO’s engagement with non-State actors can involve risks which need to be effectively managed and, where appropriate, avoided. Risks relate inter alia to the occurrence in particular of the following:
(f) the whitewashing of a non-State actor’s image through an engagement with WHO; …”)
The earmarked financial contributions from GSK, Novartis and Roche are in the following areas: epidemic prone and pandemic prone diseases, neglected tropical diseases, alert and response capacities, strategic communications, access to medicine and health technologies and strengthening regulatory capacity for vaccine-preventable diseases, tuberculosis and malaria. These areas are closely linked to the commercial interest of the companies. Their activities related to vaccines and medicines fall within these areas.
Even though there is no information about the exact activity for which these financial resources have been used the financial contributions from these pharmaceutical companies raise prima facie concern with regard to the violation of paragraph 15 of the Guidelines that states: “Funds may not be sought or accepted from enterprises that have a direct commercial interest in the outcome of the project toward which they would be contributing, unless approved in conformity with the provisions on clinical trials or product development, set out below”.
These financial contributions thus raise doubts about the implementation of the Guidelines by the Secretariat. How can the WHO Secretariat be expected to scrutinise the conduct of the pharmaceutical companies concerned while accepting financial resources from them?