I. MODEL GUIDELINES ON CONFLICT OF INTEREST

A. Introduction

This document presents policy on “‘conflict of interest” as it applies to external evaluators and members of advisory committees. These two categories of person are together referred to as “consultants” for the purposes of these guidelines.

A model proforma for a signed statement on conflict of interest is in Section II of this Annex.

B. Conflict of interest

Definitions and Principles

The common meaning of “conflict of interest” is a conflict between an individual’s private or personal interest and his or her duty. However, it may also refer to a situation where an individual has several duties which conflict without involvement of any private or personal interests.

A conflicting private or personal interest may be financial or non-financial:

(a) When a decision-maker or consultant has a direct financial interest, however slight, in the matter to be decided, there is a conclusive presumption of bias and the decision-maker or consultant will thus be disqualified from acting.

(b) Where a decision-maker or consultant has a non-financial interest which gives rise to a reasonable presumption of bias, the decision-maker or consultant will be disqualified from acting. The test here is whether a reasonable observer would suspect that there is a possibility of bias, not whether that bias actually exists. A relevant non-financial interest may arise, for example, out of personal or family involvement between a decision-maker or consultant and a party whose interests are affected by the decision or recommendations. Such an interest may also arise where a decision-maker or consultant is seen to have prejudged the issues, either through preconceived opinions or prior involvement with the facts of a case on which he or she is required to make a decision on recommendations.

Conflict of interest in relation to consultants

There are variety of situations in which consultants may find themselves in a situation of conflict of interest between their professional activities (e.g. preparation of objective and independent evaluations, membership of independent committees) and personal and private interest (e.g. private consultancies, grants to cover travel and accommodation at company-sponsored conferences, share holdings, research grants, honoraria). It is recognized that almost all consultants have some potential conflict of interest because of their present or past association with the pharmaceutical industry.

Some situations of conflict of interest are clear cut and some are more difficult to determine. If an individual is an employee of, or a retained consultant to, a pharmaceutical company, there is a clear possibility of conflict of interest. If an individual is an employee of a government organization, does no work on behalf of pharmaceutical companies, and is not in receipt of gratuities or funding, there is minimal risk. Between these two situations is a spectrum of possibilities where the decision may be less obvious.

Contracts are unlikely to be offered to consultants in any one of categories 1 to 6:

1. The consultant works in the pharmaceutical industry, including pharmaceutical consultant companies, either as an employee or as an owner or part-owner (e.g. owner of a consultancy or shareholder in the pharmaceutical company).

2. The consultant receives a retainer (fee) from one or more pharmaceutical companies whose products she or he has to assess or which the new product is likely to replace.

3. The consultant has a significant direct current relationship with one or more companies. This may take the form of (a) financial support for an ongoing research project or projects (b), sponsorship of graduate or postgraduate students, or (c) company employees who are under the direct responsibility of the consultant.

4. He or she receives substantial financial assistance or expensive equipment to conduct research on behalf of the pharmaceutical company.

5. The consultant acts or has acted as a consultant for a pharmaceutical company on the product she or he has agreed to assess. Such a consultancy may include sponsorship as a speaker, or appointment as chairperson at professional meetings concerning the product, or attendance on behalf of the sponsoring company at national or international professional meetings concerning the product.

6. The consultant has had significant input to the planning or conduct of a clinical trial of the product, for example as a principal investigator, signatory to the study report, or author of any published or unpublished paper or other report of the study. Participation limited to the inclusion of patients in a large-scale multicentre study is not considered a significant conflict of interest.

A conflict of interest is less likely to be seen in situations 7 to 10:

7. The consultant has occasional contracts with one or more companies for particular projects, but does not have a significant relationship with any one company. She or he has not been directly involved with the product in question.

8. The consultant owns or works for a consultancy which does not provide advice to the pharmaceutical industry but may provide advice to other industries, such as the devices, food or paint industries.

9. The consultant occasionally provides advice to one or more companies on the design of clinical trials to be conducted prior to submission of an application for marketing authorization, but does not have a significant ongoing relationship with any one company (e.g. points 1 to 6 above).

10. The consultant has been invited to attend and contribute to national or international meetings organized by professional or academic associations.

The responsibility of consultants

A DRA cannot be aware of all of a consultant’s involvements and their ramifications when a contract is offered. The onus is therefore on the consultant to declare in writing any potential conflict or what may be seen as a potential conflict to the DRA staff member who negotiated the contract or committee membership. If there is any doubt, the potential conflict must be declared.

The consultant may only proceed with the evaluation of the data or committee membership after any potential conflict has been discussed with the DRA and found not to be significant.

For this reason, each evaluation contract requires the evaluator to sign a statement to the effect that she or he has no current conflict of interest and that, if the risk of such a conflict arises during the evaluation, the DRA will be notified immediately in writing.

The evaluator is expected to cease reading the application immediately she or he becomes aware of a conflict of interest, and return it promptly to the DRA.

C. Confidentiality

Any data concerning a company’s product which are supplied by the DRA to a consultant for review are strictly confidential. As stated in the contract, all materials included in contract material must be accepted in strict confidence and held in safe and secure custody at all times. An application may be discussed only with DRA staff members.

Consultants must be aware of and avoid the possibility of indirect breaches of confidence. There is clearly a potential, consciously or subconsciously, to misuse information gained from a consultancy in other papers or scientific presentations on the product in question. Such a case would also constitute a conflict of interest. The consultant must not use information gained in this way in future scientific papers or presentations without the agreement of the company or individual who submitted the data.

D. Impartiality

To protect impartiality, the company concerned is not informed by the DRA of the consultant’s identity when applications, data or committee papers are forwarded to a consultant. For this reason, the consultant should have no direct communication with the company concerning the product. The consultant may not disclose his or her role to the company, even after a decision on the application has been completed.

E. Subcontracting the evaluation

A consultant is not allowed to subcontract part or all of an evaluation to any second person without written permission from the DRA. If the DRA agrees to such an arrangement, the consultant must ensure that the subcontractor is fully aware of the provisions on conflict of interest, confidentiality and impartiality set out in these notes.

If any part of an evaluation is subcontracted, the person who actually undertakes the work must also sign all reports to which she or he has contributed.

II. MODEL PROFORMA FOR A SIGNED STATEMENT ON CONFLICT OF INTEREST

It is not necessary for external evaluators to sign this proforma if they have signed the proforma external evaluation contract (see Annex 5) because the same declarations are included in the proforma contract.

I have agreed to participate in meetings of the committee known as

For the purposes of my membership of this committee, I declare as follows.

1. I do not hold any office, possess any financial or non-financial interest, or have any obligation whereby, directly or indirectly, duties or interests are or might be created which would conflict with my duties and interests as a member of this committee.

2. If, while participating in committee activities, either during a meeting or when reading or preparing papers for the committee, a conflict or an immediate risk of a conflict arises, I will immediately notify the [name of regulatory authority] of that risk and will cease the activity.

3. I will not disclose or make public any material which becomes available to me as a result of my membership of this committee, either during my membership or after my membership has ceased, without prior approval in writing from [name of regulatory authority], except for information that is demonstrably in the public domain.

Name and address: ......................................................................................

Signature: ...............................................................................

Date: ...............................................................................