Title I - PROVISIONS OF THE CODE
CHAPTER II - Interaction with Healthcare Professionals and Organizations
14.1. Clinical Trials
A clinical trial is any research conducted on humans to determine or confirm clinical, pharmacological and/or other pharmacodynamic effects, and/or detect side effects, and/or study the absorption, distribution, metabolism and excretion of one or more medicines under study for the purpose of determining their safety and/or efficacy.
Pharmaceutical companies must conduct this type of study in compliance with applicable legislation, after receiving a favorable ruling from the Clinical Research Ethics Committee, the agreement of each of the Centers where the research will be conducted and authorization from the Spanish Agency of Medicines and Medical Devices (AEMPS in its Spanish acronym).
14.2. Post-Authorization Studies
Post-authorization studies are any clinical or epidemiological study conducted during the commercialization of a medicine according to the conditions authorized on its summary of product characteristics, or under normal usage conditions, in which the medicine or medicines of interest are the fundamental exposure factor being investigated. These types of studies may be conducted as clinical trials (art.14.1) or as observational studies.
An observational study is a study in which medicines are prescribed in the usual manner in accordance with the conditions established in the marketing authorization. Assigning a patient to a specific therapeutic strategy will not be decided ahead of time by the study protocol, but instead it will be determined by routine medical practice and the decision to prescribe a given medicine will be clearly separated from the decision to include the patient in the study. No intervention will be applied to any patient, be it diagnostic or monitoring, that is not a part of routine clinical practice and epidemiological methods will be used for analysis of the data collected.
Post-authorization studies of an observational nature will be those epidemiological studies that meet the conditions of being post-authorization and observational. These studies must be conducted in compliance with the requirements of applicable legislation, including the presentation of documentation to the AEMPS for registration and classification, presentation to a Clinical Research Ethics Committee for evaluation, etc. These studies must in no case be conducted as a procedure for promoting a product or for the purpose of influencing prescribing habits.
Legislation also contemplates conducting observational studies that are not post-authorization (Non-PAS). These are observational studies in which the primary exposure factor under investigation is not a medicine, as is the case, for example, in disease prevalence or incidence studies. These observational studies must also be conducted in compliance with the requirements of applicable legislation.
14.3. Market Research Studies
Market research (including social and opinion research) consists of the systematic compilation and interpretation of information on individuals and organizations using statistical and analytical methods and social science techniques that are applied in order to obtain new perceptions or to provide elements that support decision-making.
In these studies, the identities of the interviewees are not revealed to the user of the information without their expressed consent, nor are interviewees contacted for sales activities that result from the information they provide.
Notwithstanding applicable legislation, there is a general ethical framework within which market research must be conducted, as shown in the ICC/ESOMAR International Code for the Practice of Social and Market Research from the European Society of Marketing and Opinion Research (ESOMAR). In the specific case of the pharmaceutical industry, the self-regulation framework on this material consists of the European Pharmaceutical Market Research Association (EphMRA) Code of Conduct.
This regulation does not presume to replace the EphMRA Code, but instead establishes certain mechanisms that guarantee the appropriate execution of these studies in the application of this Code. The EphMRA Code will be of subsidiary application for the appropriate interpretation of this Code.
All market research studies are subject to this article if they are conducted at a company's initiative, the initiative of several companies that share business strategies for a product or when a pharmaceutical company hands the study to a third party (research institute, scientific society, etc.) that has undertaken the work at its own initiative.
Market research studies must meet the following requirements:
i) Blinding of the identity of the persons participating in the study. The pharmaceutical company will not have the ability to learn before, during or after the study, the identity of the individuals participating in the study.
ii) Anonymous nature of the information collected.
The pharmaceutical company will not have the ability to associate the data or opinions obtained with the names of the participants.
iii) Aggregate handling of the responses or data obtained.
iv) Proportionality between the universe and the sample. Quantitative market research studies pursue a level that is representative of the universe. When calculating sample size, if parameters other than those generally used in market research studies (simple random sample, 5% margin of error, 95% confidence level and 50% level of heterogeneity),the prior approval of the Code of Practice Surveillance Unit will be necessary.
v) The individual who participates in the study does not know and does not have the opportunity to link the study with the pharmaceutical company or with a specific product. Therefore, the pharmaceutical company’s sales network cannot play any role in developing and conducting the study.
vi) The results of the study and the data obtained will not be published or used in promotional materials.
Any exception to these requirements must receive prior approval of the Code of Practice Surveillance Unit. In particular, the requirements of i, ii and v are included in the Supplementary Rules for market research studies associated with a product.
In addition, in order to guarantee that the marketing research studies do not represent an inducement to prescribe, or may contain an incentive that is prohibited under the Code, pharmaceutical companies undertake to:
a) Communicate the study prior to its commencement, in accordance with the provisions of Title II Rules of Procedure for the Control Bodies.
b) Ensure that the study does not modify the physician's prescribing habits or the pharmacist´s dispensing habits.
c) To have a written protocol that clearly establishes the objectives, methodology, anticipated results and use. In this regard, written agreements will be formalized with the professionals and/or entities with whom the studies will be conducted on the one hand and the company sponsoring the study on the other, specifying the nature of the services to be rendered, the conditions for participation and remuneration to the professionals, etc.
d) Remuneration to participating professionals must follow market criteria and be in accordance with the time spent, the work performed and the responsibilities assumed. In addition, it must be appropriately formalized. Remuneration must be monetary. In exceptional cases and with the prior authorization of the Code of Practice Surveillance Unit, remuneration may be provided in kind.
e) Guarantee that the conduction of the study does not constitute an inducement to recommend, prescribe, purchase, supply, sell or administer medicines.
f) Be approved, prior to execution, by the company's scientific department or by the Compliance Officer stipulated in article 12.11 of the Code.
These requirements will be applicable regardless of the methodologies, sources or techniques applied to implement them, for example: survey method, observation, experimental designs, ethnographic techniques, expert groups, qualitative techniques, etc.
Failure to communicate studies referred to in this article 14.3 that are required to be reported will constitute a violation of this Code.
14.4. Any other type of activity, practice or initiative that collects information not considered in the previous sections or in article 16 of the Code that involves direct or indirect remuneration of Healthcare Professionals will qualify as a promotional action and, as such, will be subject to the provisions of this Code, particularly as stipulated in article 10 (Guarantees of Independence).
14.1. Pharmaceutical companies must provide detailed information on clinical trials in accordance with current legislation and the stipulations of the "Joint Position on the Disclosure of Clinical Trial Information via Clinical Trial Registries and Databases 2009 and the Joint Position on the Publication of Clinical Trial Results in the Scientific Literature 2010", available at http://clinicaltrials.ifpma.org.6
The Spanish Agency of Medicines and Medical Devices (AEMPS) has developed and launched the Spanish Clinical Studies Registry (REec), which can be consulted at https://reec.aemps.es. This site offers information on clinical research on medicines with marketing authorization being conducted in Spain.
14.2. Post-authorization studies may be conducted for the following purposes:
- To determine the efficacy of the drugs, meaning their beneficial effects under routine clinical practice conditions, as well as modifiable factors such as therapeutic non-compliance, polymedication, disease severity, presence of comorbidities, special groups (elderly, children, etc.), genetic factors or lifestyle-related factors.
- To identify and quantify the side effects of the medicine, especially those that were not known prior to marketing authorization, and to identify possible risk factors or effect modifiers (demographic characteristics, concomitant medication, genetic factors, etc.).
- To obtain new information on medicine usage patterns(dosage, treatment duration, appropriate use).
- To evaluate the efficiency of medicines, meaning the relationship between the health outcomes and resources used through the use of pharmacoeconomic analysis.
- To learn the effects of medicines from a patient's perspective (quality of life, satisfaction with treatments received, etc.).
14.3. In compliance with the conditions stipulated in the ESOMAR Code, companies may only access the identity of participants for the purpose of supervising and controlling the quality of the study. For this purpose, access to this data will be temporary while quality control activities are being conducted and no record of data from participants may remain in the possession of the company.
There are market research studies that have the objective of learning the opinion of Healthcare Professionals on a specific medicine, to study interest in a product based on its strong or weak points, or, for example, to analyze materials that will be used to provide information about the product's characteristics, etc. In these cases, the Healthcare Professional who participates knows, or may know, the pharmaceutical company that is developing said study and, in addition, when the aim is to test the content, comprehension, design, ease of presentation or interest in the materials used by companies to promote their medicines, personnel from the company's marketing or sales departments may also be involved.
Because of their nature, market research studies on a product will only be remunerated when strictly necessary and must be conducted on very small sample sizes. When in doubt, companies must take the ruling of the Code of Practice Surveillance Unit on this matter into account.
Regardless of the study being under taken, when remuneration is provided, this must be of an ancillary nature. Therefore, not only should market criteria and the time used, the work performed and the responsibilities assumed by the professional be taken into account, it should also be proportional to the aims of the study.
The purpose of communicating studies is to facilitate the monitoring work of the Code of Practice Surveillance Unit. In no case should this be understood as implying authorization. The companies continue to be solely responsible for compliance with the Code in these studies, regardless of whether or not they are communicated previously to the Code of Practice Surveillance Unit.
6 Joint declaration of IFPMA, EFPIA and JPMA.