The Impact of Off-Label, Compassionate, and Unlicensed Use on Health Care Laws in Preselected Countries

Pressure to conduct off-label, unlicensed and compassionate use, which are hereafter summarized under the term nonlicensed drug use (NDU) is exerted onto health care professionals (HCPs) in times of situational therapeutic impasse. Liability, contractual and penal risks are present when treating a patient in a nonlicensed was. There is a gap of knowledge about institutional and governmental methods of resolution concerning off-label, unlicensed and compassionate use. Hypothesize is however, that strategies to manage off-label, unlicensed and compassionate use have evolved in different countries. The research problem of this thesis is thus to compare the effects of NDU on pharmaceutical legislation in selected industrial countries and to determine strategies brought forth by NDU. Furthermore, the development of a general regulatory approach to the management of NDU is sought. A regulatory approach shall consider existing conventions and means already available in the present regulatory world. <br /> Semi-structured qualitative interviews, comparison of laws, and literature re¬search i.e. triangulation, was the scientific methodology chosen to address the research problem. The study was undertaken in Canada, the U.S., U.K., Japan, France, Germany, Switzerland, Austria and the transnational E.U. 44 semi-structured qualitative interviews were conducted with 47 selected representatives of different roles from five areas of interests and in each country. The emphasis of this comparison of the impact of NDU laid on terminology for NDU, supply and necessity of NDU, pharmaceutical promotion of NDU, legal responsibility for NDU and public policies related to NDU. Social legislation was not considered.<br /> Key findings from the survey included miscellaneous synonyms for NDU, multiple definitions for NDU and different classes of off-label, unlicensed and compassio-nate use. Two important results from the current literature on supply and neces-sity derived: There is a circumstantial need for off-label, unlicensed and compas-sionate use, but isolated evidence suggested non-rational NDU intermittently. Furthermore, the comparison of laws showed legal obligations of physicians to perform off-label, unlicensed and compassionate use. Another outcome was proof of inappropriate off-label marketing on the part of MA holders (MAH). On the other hand, a demand for information on NDU on behalf of HCPs was present. Obtained results illustrated cross-liability for HCPs and MAH. Special use authorizations, which were recommended by interviewed representatives, were found. Pharmacovigilance in NDU was seen to be either intensified in the scope of special use authorizations or else relied on routine adverse drug reaction (ADR) reporting. Finally, results demonstrated regulatory strategies of different efficiencies: In the E.U. for instance, incentives for new indications were (a) limited to one year or (b) restricted to (i) pediatrics or (ii) rare disorders. This was found to probably be insufficient, because a drug may be appropriate for multiple indications or much-needed in fields of medicine other than pediatrics or rare disorders. <br /> The absence of statutory terminology causes incoherent interpretation of NDU across the researched nations; harmonization is crucial for an effective concept development. There is a situational need for early access to unapproved treat-ments. Denial of (nonlicensed) treatment is considered unethical. Databases to combat data shortage about NDU are operated intermittently in different settings. On the other hand, isolated evidence also highlights inappropriate marketing of NDU, which perhaps causes irrational NDU. Different effective regulatory strategies are at hand for patient access to off-label, unlicensed and compassionate use of medications in the short term. If present, these so-called special use authorizations are accompanied by drug safety measures exceeding customary ADR reporting and providing for pharmacovigilance, which otherwise would be absent. Special use authorizations define the liability and provide legal certainty. In the long term however, demand-driven approach to marketing authorization (MA), not neglecting the fact that a single drug may be appropriate in many indications, is crucial. Proposed solutions for an enduring management of NDU are firstly, the amendments of templates by competent authorities to include appropriate off-label use, secondly full MA of innovative MPs used compassionately and thirdly an amended German standard MA for essential unlicensed drugs.

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