FMT harmonized regulations are lacking and the current regulatory status ranges from non-existing to strictly regulated (35). For now, the US FDA had classified FMT as a live biotherapeutic drug that requires the submission of an Investigational New Drug application for its therapeutic uses (36). CDI has been recently exempted from IND application filing, which was a decision that was received with high appreciation by clinicians to use FMT in a fatal ailment. Meanwhile, strict regulation and control over the use of such treatment were recommended by, Renzong Qiu, 2017 (44). Moreover, although, FMT has recently received great attention there is still a gap in the understanding of FMT around the world, even in countries using it (45, 46). A wider acceptance of this therapy can be achieved by the implementation of regulations addressing the ethical and social issues facing its application such as the autonomy and the privacy of patients and donors, promoting research investigating its safety and efficacy, and the use of standardized methods in its preparation and application including stool banking (14, 18, 19). Moreover, to promote its dissemination to countries in the Middle East. such as Jordan, then country specific social norms, tradition, customs and religious backgrounds, and structures should be taken into consideration towards introducing and regulating FMT (44).
Our results demonstrated that the majority of the respondents heard of FMT treatment but did not practice it. In contrast to Jordan, where FMT is not regulated nor practiced yet, FMT has been practiced in China since the fourth century where traditional Chinese medicine used yellow soup, fecal slurry, orally to treat food poisoning and diarrhea (28, 47). This justifies the high familiarity of this treatment modality among Chinese clinicians (28). Nevertheless, the familiarity does not guarantee experience in using it by clinicians; Zipursky, et al. (48) in their study reported that physicians have limited experience with FMT despite having treated patients with multiple recurrent CDIs.
In general, our study population was not enthusiastic about nor supportive of the introduction of such treatment. They did not see its promising utility for other future applications. Barriers towards the promotion and recommendation of FMT include mostly the absence of official guidelines and regulations followed by the risk of infections and long-term risk and safety. This is in concordance with Kelly et al.(49) who reported on physicians’ attitudes towards FMT in 2010 at the American College of Gastroenterologist meeting. They found that 40% of physicians who had heard of FMT were not willing to try it, pending further demonstration of its efficacy safety. Nevertheless, Kelly et al., showed that physicians’ recommendation was positively influenced by patients' perceived acceptance(49, 50). This was not what our respondents think. In general, unwillingness for recommending FMT treatment were related to many factors; the limited knowledge among the study population (38), the limited practicing numbers (40), and the “yuck”factor (51). Other reasons for physicians not offering or referring a patient for FMT were; "not having the right clinical situation’, "the belief that patients would find it too unappealing", and "institutional or logistical barriers" (48). In his commentary, Brandt et al., (51) related physicians' hesitation to recommend FMT to the limited randomized controlled trials to show effectiveness and safety. He predicted that patients' needs in addition to the availability of aesthetically acceptable formulations are influential parameters towards the acceptance of this treatment modality among physicians. Indeed, we found that the lower part of GI was the only acceptable route of administration of FMT. This might affect how the accepted FMT formulation will need to be regulated in Jordan in the future.
In support of the international legislations, our respondents will not recommend FMT as a first-line treatment, but only recommend it when there is a failure of conventional treatment or they want organic natural treatments. This is in agreement with the Iranian clinicians and gastroenterologists' attitudes who reported a willingness of accepting FMT as a therapeutic option if it is scientifically justified and ethically approved given it was used as synthetic microbiota rather than FM (52).
Clinical efficacy is a crucial factor that maintains patients’ positive attitudes towards fecal microbiota transplantation (53) and physicians advising and referring patients to FMT treatment modality. The reported physicians’ responses regarding the efficacy and safety of FMT were diverse. While a major concern about FMT efficacy and safety was reported among Chinese clinicians (43), Zipursky et al., (48) have reported minor doubts about FMT's efficacy and safety among physician respondents at Dartmouth-Hitchcock Medical Center and Baylor College of Medicine (Texas, USA).
In light of the above-described barriers and limited efforts in increasing the awareness of the uses and efficacy and safety of FMT treatment modality, we predict that the introduction and the regulation of this treatment modality in Jordan is not going to be soon. Accordingly, efforts should be put forth for increasing awareness about its utility and effectiveness and to highlight the ethical and cultural/religious challenges towards its application such as patients' vulnerability, donor’s anonymity and data de-identification and the consenting procedure Moreover, legislative and ethical challenges facing the establishment of biobanks in Jordan including privacy and confidentiality, specimen ownership and informed consent should be addressed (54). According to the US FDA, during the investigational use of FMT, the potential risks and benefits including the unknown risks and the long-term risks should be clarified for qualified patients during the consenting procedure (Food and Drug Administration 2013). Consenting is an ethical challenge in FMT, which was recognized by close to 50% of our participants. The FMT consenting procedure should consider patients' vulnerability, unforeseen long term risks, and limited knowledge of the actual benefits and risks to the treatment in addition to the universal ethical requirement of biomedical research (55) . Ma et al., (2017) (28) believe patients' compromised decision-making capacity and vulnerability are the main challenges to informed consent. They consider CDI patients vulnerable, and desperate individuals who can be easily affected by emotive language as being natural and safe whether from physicians or the media. This was opposed by Bunnik et al., 2017(13) who believe that it is not the vulnerability or capacity to consent but rather the inadequate information that poses difficulties with regards to the FMT consenting procedure.
Other important challenging parameters in the consenting process are cultural/religious or personal/ideological food restrictions () of stranger donor. In their commentary, authors questioned whether informed consent to FMT can be obtained without information about the donor’s diet. This an important ethical challenge that is very relevant to our region’s population that is mostly Muslim thus observing the religious commitment to halal nonalcoholic containing foods and beverages is essential. Our respondents think that religion, dietary, and alcoholic consumption will be considered as a barrier in patient's acceptance of FMT. Accordingly, we perceive that it could be necessary to declare the donor’s dietary habits to obtain an autonomous decision in this region.
An important parameter that was highlighted by the respondent's comments was the need to consider the religious point of view and to seek Fatwa. This was declared by 30% of the participants in addition to their perception of the need for more knowledge about safety. Therefore, we concluded that our health care practitioners are reluctant to use FMT because of concerns about safety and religious beliefs. Ma et al., 2017 (56) highlighted important cultural and religious beliefs that might affect the public acceptance of FMT. Some people might consider FMT an unsanitary treatment, and some will limit the donor to those who eat specific food, as vegans, or those with a specific religion such as Muslim patients who might not accept fecal transplant from non-Muslim donors. All these barriers entail the importance of demarcating region-specific FMT regulations that take into consideration the cultural and religious background of the public.
Although, there is a growing awareness of ethics in human research, nevertheless Alahmad et al., 2012 have shown that research ethics regulations and guidelines in Middle Eastern Arab countries suffer from various degrees of deficiencies with regards to ethical protection (57). They recommended that social norms, traditions, customs, and familial ties should all be taken into consideration when developing policies and regulations. In interviews with medical professionals from the Middle East Alahmad et al., 2015 (58) reported the social importance of protecting confidentiality, de-identification, and anonymity of donors scored 100% as being an ethical concern in conducting FMT among the Jordanian clinicians. They mostly agreed that confidentiality can be protected by double blinding both the donor and the receiver and to ensure the confidentiality of patient information during communication with others.
Limitations:
Firstly, our study adopted convenient sampling from the capital of Jordan (Amman), therefore the findings may not be generalizable to other provinces or worldwide. However, the objective of this study was to assess the perceptions of health care providers, regarding ethical and social concerns about FMT, as the first such study among this population and we do not expect our results will substantially change among other Jordanian physicians. Secondly, we had a limited number of physicians who used FMT, making it more difficult to fully comprehend the procedure and its risks and benefits and the attitudes might change if they had a positive experience in treating patients with it.
In conclusion, our study demonstrated a lack of enthusiasm to implement FMT in Jordan by health care providers although there is general support for its potential use as a second line of treatment when other traditional medical treatment fails. There are complex ethical, religious, and practice-based challenges that need to be addressed before FMT becomes an established practice. Future studies should examine FMT from local traditional and especially religious perspectives as well as other barriers found in our study, as well as consenting, privacy, and risks. Patient (end-user) perspectives are lacking and would be important to understand the level of acceptability among those who need FMT. Furthermore, there should be more education to increase the understanding of FMT benefits and risks among Jordanian health care practitioners.