TRIPS and disclosure of clinical information: An intellectual property perspective on data sharing

• DOI: http://doi.org/10.1111/jwip.12071
• Date: 01 March 2017
• Published date: 01 March 2017
• Author: Gabriele Spina Alì

DOI 10.1111/jwip.12071

ORIGINAL ARTICLE

TRIPS and disclosure of clinical information: An

intellectual property perspective on data sharing

Gabriele Spina Alì

Faculty of Law, University of Hong Kong,

Hong Kong

Correspondence

Faculty of Law, University of Hong Kong,

10/F Cheng Yu Tung Tower, Centennial

Campus, Pokfulam Road, Hong Kong.

Email: gabriele.spinaali@gmail.com

Health scholars, lawyers, and social activists have greatly emphasized

the social benefits of disclosure of clinical reports, that is, dossiers of

drugstrialssubmittedtomedicalagenciesin support of pharmaceutical

authorizations. On their side, medical authorities are reluctant to

divulge regulatory documents because they fear that they might

contain commercial trade secrets of drug applicants. In these regards,

the Agreement on Trade Related Aspects of Intellectual Property

(TRIPS) prohibits trials disclosure except “where necessary to protect

the public”or “unless steps are taken to ensure that the data are

protected against unfair commercial use.”This paper delves into the

complicacies of the TRIPS discipline to clarifythe limits imposed by the

treaty on medical agencies, and it goes on to suggest meaningful ways

of complying with the TRIPS obligations while retaining most of the

benefits associated with trials disclosure.

KEYWORDS

clinical trials, data exclusivity, disclosure, TRIPS

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TRIPS AND DISCLOSURE OF CLINICAL INFORMATION

In most jurisdictions, a pharmaceutical is authorized into a market only after a specialized state agency has evaluated

its safety, quality, and efficacy. Evidence of these characteristics is usually provided by a sponsor through the

submission of a dossier containing detailed reports of the outcomes of clinical testing on human subjects, alongside

with other relevant information. Theoretically, publication of this information may occur at the end of regulatory

approval, or, to a lesser extent, at an earlier stage. This is the case of trials registration immediately after the

recruitment of the first volunteers, or when authorization to start experimentation is granted.

However, the confidential status of the clinical dossier is still highly debated. Experience shows that governments

are often reluctant to share trials information because it might contain confidential commercial information. At a

The findings and the conclusions of this paper are part of the research conducted by the author at the University of Hong Kong

for the degree Doctor of Philosophy, under the precious supervision of Ms. Alice Lee.

© 2017 The Author. The Journal of World Intellectual Property © 2017 John Wiley & Sons Ltd

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wileyonlinelibrary.com/journal/jwip J World Intellect Prop. 2017;20:24–56.

domestic level, the confidentiality of the clinical dossier depends on pharmaceutical and administrative laws,

intellectual property rules, and the policy on data disclosure adopted by medical agencies and registries.

On the other side, a united front of public and private agents fights for the abolition of the confidentiality status of

clinical studies. Health scholars, lawyers, institutional bodies, and non-governmental organizations have all advocated

for the integral disclosure of the clinical dossier to the public.

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In particular, they have emphasized the social benefits

of trials dissemination in achieving important health objectives, and how these public goals should necessarily offset

any private interest in data confidentiality (e.g., Gøtzsche, 2011; Lemmens & Telfer, 2012). Now, while these claims

are solidly grounded and worthy of deeper discussion, these debates have often overlooked at the intellectual

property dimension of open access policies.

In many jurisdictions, clinical trials are subjected to a sui generis form of intellectual property, that is, data

exclusivity, which often imposes as a collateral obligation a non-disclosure obligation to medical agencies. In these

regards, the Agreement on Trade Related Aspects of Intellectual Property (TRIPS)—the most comprehensive and

important intellectual property treaty of the 20th century—deals directly with clinical trials disclosure. Article 39.3 of

the agreement stipulates that: “Members, when requiring, as a condition of approving the marketing of

pharmaceutical or of agricultural chemical products ... the submission of undisclosed test or other data ... shall

protect such data against unfair commercial use. In addition, Members shall protect such data against disclosure,

except where necessary to protect the public, or unless steps are taken to ensure that the data are protected against

unfair commercial use.”

At a first glance, the treaty text seems utterly bizarre. While the beginning of provision impose s to protect data

“against unfair commercial use,”the second part allows disclosure in case parties comply with its first half. But, since

protection against unfair commercial use is already mandatory, the non -disclosure obligation under Article 39.3

seems devoid of any legal value. Hence, it does not surprise that interpr eters are still struggling to unravel the

meaning of the treaty text. Unfortunately, ambiguous as it might be, Article 39.3 remain s a binding part of the TRIPS

agreement, both for member states and indirectly for their medica l authorities.

Themain goal of this paper is to make senseof the inherent contradictionin the provision, in order to elucidatewhich

obligationsare posed to medicalagencies while settingtheir data access policies. Indoing so, the paper will be structured

as follow: after a short briefing on what clinicaltrials are, and what legal problems they pose, the advantages of data

disclosureand the position of the pharmaceuticalindustry will be illustrated.The paper will continue with an analysisof

the meaning of Article 39.3TRIPS and it will propose effective ways for agencies to comply with theTRIPS discipline

while trying to reap the benefits of data disclosure. The last chapters will contain a brief assessment of the current

policies of some countriesand a final reflection on disclosure and dataprotection.

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CLINICAL TRIALS: THE HISTORICAL AND LEGISLATIVE OVERVIEW

Clinical trials may be described as “a research study in human volunteers to determine whether experimental

treatments are safe and effective under controlled conditions and whether they should be approved for wider use in

the general population”(Lee, Lee, Wu, Lee, & Chen, 2006, p. 1). Tests of some sort have probably been performed

since early ages, and trace of a testing of a vegetarian diet on a group of 10 people is even described in the Book of

Daniel in the Christian Bible (Day & Ederer, 2004, p. 3). Documented practices of clinical testing started in the 18th

century and received a fundamental boost in the 19th century with the pioneer endeavors of Johannes Fibiger. He

compared his diphtheria serum with the standard treatment, by randomly dividing trials participants in two groups.

This gave an important boost to the modern understanding of randomization as a central feature of clinical trials

experimentation (Peppercorn, Roberts, & Hammond, 2009, p. 118). The practice of randomization found a final

consolidation in the 20th century: when in 1946, the British Medical Council tested the drug streptomycin on

97 patients, the half of which were only given control treatment (Peppercorn et al., 2009, p. 120). Few years later, in

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1951, the first randomized trials study was performed in the United States by the National Institutes of Health (Day &

Ederer, 2004, p. 4).

Unfortunately, legislators understood the importance of clinical testing only after two medical tragedies

dramatically hit the European and American populations, provoking the resentment of the general public. In 1937, the

commercialization of Elixir Sulfanilamide in the US territory caused a mass poisoning leading to over 100 casualties. As

a response, in 1938, the US Congress enacted the Federal Food, Drug and Cosmetic Act, the first legislation to

expressly require clinical trials in support of a drug safety before it could be authorized into market (Akst, 2013; FDA,

1981; Wax, 1995).

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Similarly, the Thalidomide disaster, which in the 1960s caused hundreds of children to be born

with deformities both in Europe and United States, pushed the European bodies to evaluate drugs safety before

allowing public distribution (Kim & Scialli, 2011; Ridings, 2013).

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Clinical trials regulations have significantly evolved during the years. For instance in 1962, the US Congress

amended the Food, Drug and Cosmetic Act to require evidence of efficacy besides safety and quality.

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To keep up

with scientific progress, medical agencies as the American Food and Drug Administration (FDA) and the European

Medicines Agency (EMA) routinely approve detailed disease-specific guidelines implementing new clinical trials

standards and procedures.

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Internationally, the International Conference for Harmonisation of Technical Requirements

for Registration of Pharmaceuticals for Human Use (ICHR) was created in 1990 to create a platform for the regulatory

authorities of United States, European Union (EU), and Japan to discuss and harmonize clinical trials protocols in the

three territories. This allows companies to submit the same English protocol in the three jurisdictions (Baber, 1994;

Singh, 2015). The platform continues to operate under the name of International Council for Harmonization and it is

now a legal entity operating in Switzerland.

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As a result of strict legislation, clinical testing is nowadays a long and large-scaled process which is usually

articulated in three to four phases:

Phase I: It is aimed at assessing the drug safety, and in particular its pharmacodynamics (i.e., its absorption and

metabolism) and pharmacokinetics (its interactions with targeted tissues). It is also helpful in determining the drug’s

dose and frequency of administration. This is usually achieved by running tests on a small number of healthy adult

volunteers, usually ranging between 20 and 80 subjects, for a duration that usually takes less than 12 months to

complete (Day & Ederer, 2004, pp. 12–13; Goffin, 2009, pp. 2–4; Ratain & Plunkett, 2003).

Phase II: It consists in evaluating the drug safety on the addressees of the therapeutic treatment. It is also meant to

determine the final formulation and dosing regimen of the drug, altogether with potential side effects. It is generally

designed as a randomized trials addressing a specific hypothesis by testing the compound in several hundreds

subjects (Day & Ederer, 2004, p. 13; Goffin, 2009, pp. 4–5).

Phase III: It includes randomized, double blinded control studies addressed to verify defined hypotheses about the

efficacy of the drug on control groups ranging from several hundreds to several thousands subjects. It represents

the most critical stage of pharmaceutical development, with only 25% drugs achieving positive results (Day &

Ederer, 2004, pp. 14–16; Goffin, 2009, pp. 5–6).

Phase IV: It is conducted after the compound has already been approved, in order to keep under surveillance its

safety, quality, and efficacy in the long term. It also serves the scope of detecting potential unexpected beneficial

effects that could bring to new indications in the marketing authorization (Day & Ederer, 2004, pp. 16–17; Goffin,

2009, pp. 6–7).

These four phases make clinical testing a long and costly process. According to some studies, even if highly

disputed and controverted, the cost of clinical development can easily overcome the threshold of one billion of US

capitalized dollars, the majority of which is spent in clinical testing. Moreover, the high failure rate of drug

development, with few drugs making it over phase III, renders pharmaceutical development an extremely risky

business (Mestre-Ferrandiz, Sussex, & Towse, 2012; Morgan, Grootendorst, Lexchin, Cunningham, & Greyson, 2011).

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