The following criteria were used to select studies: (1) articles that dealt with specific interventions, strategies, or policies regarding managing financial interactions between physicians and pharmaceutical companies; (2) All types of articles such as reviews, originals, etc., except Conference articles and book chapters; (3) English language; (4) Studies whose target or discussed population for intervention or strategy proposal were physicians; (5) articles whose full text was available.

A literature search was conducted on August 30, 2022. Three databases, PubMed, ProQuest, and Web of Science, were searched. The time range was considered from January 1, 2000, to 30, August 2022.

The search was conducted using the following keywords: doctor, physician, pharmaceutical, industry, interaction, relation, collaboration, payment, influence, and conflict of interest (see the complete search strategy in Appendix 1).

We used the PRISMA model for screening and selecting articles (25). All retrieved records were exported to EndNote X9. After removing duplicate articles, the titles and abstracts of the remaining articles were reviewed by two team members (EZ and AG) independently. After determining the relevance, the full text of the articles was retrieved for detailed review and data extraction.

Each article was read by two authors independently, and relevant strategies/interventions were extracted and then discussed and agreed to be mentioned in the data form.

Only strategies/interventions proposed in studies or tested in real-world settings were extracted in this review.

Data extraction and synthesis were done in two stages. First, the authors extracted interventions and strategies from the articles. These were then categorized into proposed policy options. There are two approaches to managing COI: eliminating all situations of COI by prohibitions and restrictions and controlling COI by transparency and disclosure of interactions (26). We first categorized the proposed interventions and strategies based on these approaches: 1- prohibition and restriction and 2- disclosure. In the next step, we realized that disclosure could be done from two sides: the payer (pharmaceutical companies or the industry) and the receiver (physicians). Also, industry disclosure is now voluntary and mandatory so that these options can be separated according to their specific implementation considerations.

In the second stage, we formed a team of experts. These people were selected purposefully and related to the research subject, including two physicians, two industry representatives, and three health policy experts (two of them are researchers in the field of transparency). We shared our proposed policy options with the experts' team, who confirmed our classification. In the next step, we asked the experts to tell us their opinions on these five options: “What are your opinions about the advantages and disadvantages of this policy option? What considerations should be taken into account in implementing this policy?” The interview was conducted online, and the audio was recorded. Some of the interviewees said were in the evidence, and some new points were added, especially considering the context of Iran's health system.

In the search, 579 articles were retrieved; after removing duplicate titles (232 articles), the titles and abstracts of the remaining articles were reviewed. From the remaining 164 articles, 44 were found suitable for the research topic (Figure 1). Of 44 papers, 32% (N = 14) was original, 57% (N = 25) was review articles (including seven systematic reviews), four editorial, and one RCT. Most articles were published in 2017 and 2021 (N = 6); generally, 70% of included articles were published in recent 10 years. Regarding affiliation of authors, 48% (N = 21) were related to the USA and then to Lebanon (N = 4) and Germany (N = 3). In addition, we had articles from 15 countries, including one from Iran. BMJ Open (N = 5), JAMA (N = 4), PLoS ONE (N = 3), Health Policy (N = 3), and Annals of Internal Medicine (N = 3) provided the most paper for our study. The characteristics of included papers are presented in Table 1.

A list of elicited strategies and interventions for managing COI arising from the physicians-pharmaceutical industry interaction is presented in Table 2.

In the second phase, with the collaboration of the experts' team, five policy options were proposed (Figure 2):

The policy options' advantages, disadvantages, and implementation considerations are presented in Tables 3–7.

There is a strong relationship between receiving industry benefits and supporting their products (2). Since the primary goal of pharmaceutical representatives is to promote their products—not to serve the interests of patients—so the best tactic for physicians is to avoid them (33). A concern often raised in defense of these interactions is that meetings between pharmaceutical representatives and physicians accompany the presentation of information about new drug products and allow busy physicians to stay up-to-date more efficiently (7). If the prohibition policy is implemented, the relationship between physicians and pharmaceutical representatives will be cut off, which should be addressed by designing and setting up an updated drug information system. Prohibition policy has a preventive approach toward unethical behavior and possible adverse consequences of physician-industry interaction (7). Passing and implementing the law prohibiting physician-industry interaction has many implementation challenges. Prohibition of such interactions requires legislators to formulate and pass clear and precise laws to ban all types of industry payments to physicians (7), which will probably face reactions from the medical community. Monitoring the implementation of the prohibition law is challenging and may transfer these payments to unobservable ways (such as cryptocurrency). Government regulators can reduce physician-industry COI by increasing sanctions for such activities.

An alternative policy to the prohibition is to restrict physician-industry interactions and distinguish between acceptable and unacceptable payments and gifts. Evidence shows that restrictive policies may have a positive effect on improving the prescribing behavior of physicians (38). In implementing this policy, receiving inexpensive gifts for use in the physician's office (such as notebooks or pens) and items related to patient care (drug samples and medical booklets) that do not hurt care is not prohibited, but gifts and payments such as recreational events for physicians, payment for lectures or free meals are strictly prohibited due to the increased potential for COI (2, 7). The Iranian Medical Council has also declared it acceptable gifts that benefit patients (such as drug samples for poor patients) (57). Also, according to Iran's Pharmaceutical Code of Ethics, it is allowed to accept low-value gifts, such as calendars, pens, etc., from pharmaceutical companies (58).

Implementing restrictive policies requires that medical universities and hospitals have clear and transparent procedures and guidelines for accepting gifts and payments that specify what is acceptable and prohibited. Necessary executive action determines a “threshold” above which payment should be declared a financial COI. This difficult task depends on the countries' culture, history, and wealth (33). It is suggested that COI committees be formed at the health ministry and medical sciences university level to formulate exemptions and monitor their implementation according to local conditions and the extent of the relationship with the industry.

The medical profession traditionally relies on self-regulation to implement the ethical standards of medicine and protect the patient's interests (51). When the primary goals of patient care, education, and clinical research may be threatened by financial or other secondary interests, physicians have a responsibility to self-regulate; as such, COI may undermine public trust in the physicians (8). Physicians often believe that a conscious commitment to ethical behavior and professionalism protects them from undue industry influence (59). Therefore, physicians' self-regulation relies on strengthening moral norms (60). Self-regulatory tools include voluntary disclosure, ethical guidelines, and educational interventions to reduce COI. Physician self-regulation can be implemented as a transitional policy to institutionalize a transparency culture before enforcing mandatory transparency laws.

In the Pharmaceutical Code of Ethics, as well as the Professional Ethics Guide of the Iranian Medical Council, there are cases of how to interact with pharmaceutical companies. For example, it is prohibited to give cash and non-cash gifts to physicians by pharmaceutical companies and to accept any money for travel and accommodation costs for vacations, participation in conferences, seminars, workshops, and continuing education programs from companies and industries, for themselves or their families (57). To implement this policy, it is necessary to compile a complete ethical guide by the Iranian Medical Council or the Ministry of Health to determine acceptable cases and ethical behaviors in physician-industry interactions.

Disclosure of physician-industry interactions can be made voluntarily on the physician's website or a central website. Another approach for physicians is to disclose their interactions with the industry through printed materials or a disclosure form during admission, an informed consent form, or verbally during consultation and examination of patients (19, 28). Physician disclosure does not lead to a behavior becoming ethical, but it is a step toward promoting ethical behavior (3); It can also lead to the promotion of the view among physicians that whatever is disclosed is no longer a problem (a moral license) (24). To promote a transparency culture, incentives are also determined to comply with ethics and professional norms (48).

One of the most critical executive measures in the physician self-regulation policy is empowerment, informing, and training about interactions with the industry and its consequences for physicians. Training is available at two academic levels for medical students and continuing education programs for practicing physicians. Educating members of medical professional societies on issues related to physician-industry interactions can be accomplished at annual meetings (56). These programs aim to help physicians better understand the COI associated with accepting gifts and other financial incentives and their potential impact on patient care (48). Evidence shows that educational programs are effective in increasing awareness and changing the attitude of physicians regarding their sensitivity toward interaction with pharmaceutical companies (18, 49).

Disclosure of payments and financial interactions with pharmaceutical companies can be voluntary (self-regulation) by the industry. Self-regulation allows the industry to design, implement, and monitor payment disclosure rules (27). In this policy, pharmaceutical companies are required to disclose their payments to physicians annually (30), and a trade body (such as the Pharmaceutical Manufacturers Association) supervises the implementation of the policy (16). The European Federation of Pharmaceutical Industries and Associations (EFPIA) requires pharmaceutical companies to report physician payments (36). In Australia, the Pharmaceutical Industry Association requires member companies to publicly report payments to physicians and medical facilities (16). The industry's voluntary disclosure policy is implemented in more than 30 European countries (27, 30).

Implementing this policy requires formulating regulations of minimum disclosure standards for pharmaceutical companies, which the health system can determine. The data can be published on a central platform (for example, in the UK on the Disclosure UK database) or on the company's website. Companies have considerable discretion over publishing and accessing data, leading to different reporting or general reports without detailing payments (30). The incompleteness of payment data and lack of full disclosure of them (for example, meals) is a significant flaw of the industry's self-regulation mode (27, 30). The findings of a study showed that in 23 European countries with a self-regulation approach, disclosures are published in PDF documents on companies' websites, preventing the public from understanding payment patterns (27).

One of the critical shortcomings of industry self-regulation is that it makes disclosure by paying companies conditional on recipients' consent, and a physician can request anonymity (27, 36). In this regard, there is a need to adapt the data disclosure criteria to the personal information protection law in the country. Efforts should be made to create a culture of the willingness of physicians and companies to disclose data with names and details. In this regard, individuals and companies can use financial and non-financial incentives. Due to the voluntary nature of disclosure and the less willingness of physicians and industry to disclose information, the capacity of non-governmental organizations and civil activists can be used to pressure and encourage disclosure.

In implementing the policy of mandatory disclosure of payments by the industry, a government institution such as the Ministry of Health is responsible for implementation and monitoring (16). The most famous policy in this field is the Sunshine Payment Act, which was passed in 2010 in the United States, and a system called “open payment” was launched to implement this law in 2013, which requires pharmaceutical companies to disclose their payments to physicians in this system (3). The French initiative is the Bertrand law and the Transparency Santé system (16). Mandatory disclosure regulations have also been implemented in countries such as Japan, Turkey, Portugal, Greece, Denmark, Romania, Latvia, and Slovenia (16).

Mandatory industry disclosure must be proposed in the public regulations, and the law must be approved in the parliament, which may be influenced by the lobby of the physician's union and groups. Also, disclosure standards and criteria, along with relevant guidelines, should be developed, and a searchable and user-friendly open payment system with public access should be designed (45). In this regard, there is a need for continuous cooperation and interaction between the Ministry of Health and industry representatives, and a joint office should be established for this purpose. One of the important measures of this office is to determine the types and nature of payments and financial exchanges, to select the items that do not need to be disclosed, and in general, to standardize inputs, data, time frame, and publishing methods (50).

Types of reportable payments include cash, gifts, and stock in the form of consulting fees, food, and beverage, payments for participation in continuing education programs and lectures, grants, and research payments made directly or indirectly (through a third party) to physicians. Also, ownership interests, such as shares in pharmaceutical companies, must be reported. Financial interactions exempt from disclosure can include drug samples and items with a value of <$10 per transaction or $100 per year (3). Physicians preview the data before it is publicly released and, if necessary, object to corrections.

Supporters of public reporting policies support it as a tool to manage industry influence and COI and believe that public reporting acts as a deterrent to inappropriate relationships between physicians and industry (16). Evidence shows that public disclosure reduces the recipients of financial benefits from companies (3).