Characteristics of study participants
A total of 17 researchers who have been involved either in preclinical studies or clinical trial or both participated in the in-depth interviews; eight were based at research centers, and nine at a university. Two to four interviews were conducted in each institution. Saturation of information was reached after the first 14 interviews. Ten participants had been involved in pre-clinical research, three in clinical trial, and four both in preclinical and clinical trials. The participants had experience in a diverse range of medical professional domains. Participants had between 5 and 30 years of working experience in preclinical and clinical research (Table 1). One participant have been involved in translating a study conducted on animal experiments using herbal medicine against helminth into human study up to phase-2 using a tablet formulated as a drug, but the drug was found to be inferior than the standard treatment. Another participant has been involved in the preclinical part of herbal medicinal plant against liver cancer and did not proceeded to the next step as the ethics committee didn’t allow him. Moreover, a participant has been involved in preclinical studies using herbal medicine and formulated as ointment and now they are waiting for ethical approval to conduct phase-1 clinical trial in collaboration with other research institution in Ethiopia.
Table 1: Characteristics of study participants
Terms
|
Categories
|
Number of participants
|
Area of expert
|
Pharmacology
|
5
|
Clinical pharmacology
|
1
|
Molecular microbiology
|
1
|
Biotechnology and virology
|
1
|
Infectious diseases
|
1
|
Clinical pharmacy
|
1
|
Microbiology
|
1
|
Infectious disease epidemiology
|
1
|
Pharmaceutical chemistry
|
1
|
Pulmonary pediatrics and infectious diseases
|
1
|
Epidemiology and biostatistics
|
1
|
Zoonosis
|
1
|
Trans-boundary diseases
|
1
|
Domain of experiences
|
Preclinical trials plus others
|
10
|
Clinical trials plus others
|
3
|
Both (preclinical and clinical trials) plus others
|
4
|
Years of research experiences
|
5-20 Years
|
12
|
>20 Years
|
5
|
Role as a PI in research
|
Preclinical
|
1-6 projects
|
10
|
20-30 projects
|
3
|
Clinical trial
|
1 project
|
4
|
5 projects
|
2
|
Focus area in terms of
diseases/
Pathogens/
Others
|
Studied in preclinical studies for both animal and human
|
African horse sickness, Anthrax, Anti‑infertility, Ant‑inflammation, Anti‑pyretic, Anti‑spasmodic, Asthma, Diabetic mellitus, E.coli,
Fasciola hepatica, Fowl cholera, Pasteurellosis, Leishmania,Schistosomiasis, Fowl typhoid, Haemonchus contortus, Helminthes,
Hypertension,Leishmania, Liver related diseases, Malaria, New castle disease, Infectious bursal disease, Histoplasma, Non‑communicable
Neurodegenerative diseases, Phytogenics, Rabies, Relapsing fever, Rota virus, S.aureus, Salmonella, Trypanosomiasis, Tuberculosis
|
-
|
Studied in clinical trial
|
Cervical cancer, Cholera, Diabetic mellitus, Helminthes, Hepatitis B, HIV, Malaria, Meningitis, Tuberculosis, Visceral leishmaniasis
|
-
|
Phase of study (Note: one person can conduct many studies at each phase)
|
|
Number of studies
|
Phase 1
|
5, of them 1 waiting for approval
|
Phase 2
|
3
|
Phase 3
|
4,of them 1 waiting for approval
|
Phase 4
|
1
|
Not applicable (For preclinical research and vaccine trials)
|
11
|
Type of trial for clinical trial and preclinical studies
|
Drug
|
7
|
Vaccine
|
7
|
Diagnostic tools
|
2
|
Pharmaceuticals dosage formulations on traditional medicinal plants
|
2
|
Medicinal plants
|
8
|
Challenges and opportunities for translating animal research into human trials
Using thematic analysis, six major themes were identified for challenges: lack of finance and human capacity, inadequate infrastructure, operational obstacles and poor research governance, lack of collaboration, lack of reproducibility of results and prolonged ethical and regulatory approval processes (Figure 1). Moreover, three themes were identified as opportunities: growing infrastructure and resources, improving human capacities and better administrative processes and initiatives for collaboration (Figure 2). Representative quotes supporting each theme are presented, along with unique identification numbers of participants in brackets. The themes were prioritized based on the number (frequency) of interviewees who mentioned each theme as a challenge or opportunity (Table 2, Figure 3), respectively.
Challenges for translating animal research into human trials
Lack of finance and human capacity
Nine of the participants mentioned that the major constraint for translating animal research into human trials is lack of funding. It was mentioned that translating animal research findings into human trials, particularly the clinical trial part requires a huge investment. Hence, if you do not have an adequate supply of fund from industries or other interested donors it is difficult to sustain translational research. Many brilliant Masters and PhD students who went abroad for education did not return because of that reason. Some who returned to the country after completing their education but who got the second chance to go abroad for their post docs in European and American universities did not come back because they learned that the research environment in Ethiopia was not attractive. Most academicians are frustrated to conduct thematic research projects related to translational research because of financial constraint and poor budget administration as mentioned by the study participants. The interviewees also stated that the government does not allocate enough money for translating animal research into human trials and there is a very little core research fund, which is less than five hundred thousand Ethiopian birr per annum. As reported by the participant:
“It is only the building that the government has provided. All the rest that we have managed to buy, among others, including vehicles, research laboratory equipment were secured from international funders on a very competitive basis. Some who are not able to get funding from foreign funders get frustrated and they…just compete for the local small grant which is less than five hundred thousand that can only use to cover…per diem, support MSc and PhD students work and buying simple reagents you can't even use it for fuel purchasing during field works. Unless there is core local research funding we should not expect any…real…development in the drug or diagnostic device or anything it could be used in clinical trial, we would end up in post clinical trial researches/approved drugs” (A1, clinical trial researcher).
On the other hand, two preclinical trial researchers stated that funding was not a problem; instead, it was a financial management problem.
Besides, eight participants felt that human capacity, be it from researchers’ side or the ethics experts and regulators side, was the critical factor. Respondents stated that there were poorly qualified researchers in terms of knowledge, skill, training, and experience. There is minimum awareness and preparedness, attitude problems of the research community for such type of research. Moreover, there is a poor research literacy of researchers in clinical trials and low physicians’ interest to conduct research on traditional medicine. As the study participant noted:
“…There is also an attitudinal problem in researchers…most common sign of the completion of a project is this publication. So findings from a preclinical study once they are published people do not think of taking the finding to the next level” (A8, preclinical and clinical trial researcher).
Another participant noted:
“Physicians’ interest is another challenge because they tend to the conventional medicines though traditional medicine is the mother of modern medicine as illustrated by a number of discoveries of conventional medicine which are originated from traditional medicines. So there are some blurred visions by medical doctors” (A14, pre-clinical trial researcher).
Another participant also noted that:
“…In my view the main challenge is lack of capacity of researchers in terms of knowledge and skill” (A4, preclinical trial researcher).
Problems related to regulatory and ethics committee, including the capacity of personnel in terms of knowledge, skill, and experiences to judge the advantage and disadvantage of studies is another challenge reported by the participants.
“I think it is related with…the capacity of our ethics committee in reviewing and approving studies like this [translational study] is not that much or it is limited…there is no experience so…as a country that starting…this kind of initiatives I think everybody is afraid that what if something happen and you know the level of protection you have to consider what if this study is done on myself or my family or my kids. So allowing that to happen from the ethics committee side is difficult because there is no experience and….” (A7, preclinical and clinical trial researcher).
This scientist went on to express doubt on the ethics committee in facilitating the conduct of translational study despite the fulfillment of all requirements and warned that, However, I would like also to say that no ethics committee would say no to translational study if you fulfill…whatever the GCP requirement…if the team are trained, knowledgeable skilled and if you show that you have the resource, infrastructure. But clinical trial, they do approve our clinical trial provided that you fulfill everything.
Inadequate infrastructure
While a general lack of infrastructure and facilities were thought to hinder the translation of animal research into human trials, most participants (n=9) stated that lack of well-equipped, furnished and accredited laboratory facilities and shortage of resources like laboratory supplies and consumables were major barriers. As noted by the study participant:
“So if you want to do experiments on animal models that laboratory has to be GLP accredited but there are no accredited laboratories” (A17, preclinical and clinical trial researcher).
Another scientist noted:
“No appropriate infrastructure…most of the institutes have really rudimentary kind of research laboratory and only…to support students and institutional activities…you cannot expect for big research outcomes to bring about change on the health and development of our country….” (A1, clinical trial researcher).
Another study participant also stated that:
“No facilities, for example, you know simply doing in vivo studies does not make your compound to be…eligible for a clinical trial. So you need to do…pharmacokinetics studies you need to…see the probable mechanism of action of a particular agent for that then you need to have cell lines because you can easily manipulate cell lines and it is good to understand and how the agent acts in order to produce the effect so that you could see in in-vivo experiments. So you do not have such facilities and without completing these kind of studies…it is very difficult to move into a clinical study” (A8, preclinical and clinical trial researcher).
According to the interviewees (n=2), lack of organized center specialized in translational research was also perceived as a barrier. As noted by the study participant:
“…Teaching of clinical trials that will only have trained manpower in clinical trials unless you have the institution for translational research in which these people could be engaged, I do not think it will have an input, they will end up in the university teaching on clinical trials….However, it is at least a good start and that would help to convince the government…at least to allocate for this” (A1, clinical trial researcher).
Operational obstacles and poor research governance
Translating animal research to human clinical trials demands commitment from researcher, partners and government. The participants mentioned lack of commitment from the researchers, institutions and the government to translate a scientific finding into product as major challenge.
“What I can say is that…probably low or poor commitment to translate the research finding into the product. When I say commitment, commitment from the researcher. Many researchers are just complaining…by the availability of reagent, consumables, laboratory facilities…the leadership from respective institutions or universities and the government in general. I underlined that it is a low commitment at each level if you are committed to change the preliminary product into the final product to be useful for public service then you have to committed in terms of working, extra working hours, you have to work day and night including weekend and you have to look for different opportunities and possibilities to get all the reagents and consumables” (A2, preclinical trial researcher).
Related to the research administrative environment participants perceived that lengthy and complex logistics and difficult purchasing process as another challenges which slowdowns the research conduct.
“…If you want to purchase a chemical let us say from abroad, it will take you three years by that time everything is over. Now there is much improvement but still we have to make it faster” (A15, preclinical trial researcher).
Some participants stated that lack of voluntary participation and awareness of patients as a barrier for conducting clinical trials. As stated by the participants:
“…May be related to an awareness of participants…most patients when they told us about clinical trials they think they are going to die they would not like to get consent to participate in clinical trials” (A16, preclinical and clinical trial researcher).
“…Getting patients who are voluntary to participate is also another difficulty...they do not have the culture of voluntary participation in a clinical trial unless you have a financial incentive for it” (A1, clinical trial researcher).
One participant gave emphasis on the need for a clear policy which guides the conduct of translational research that “No clear policy and central coordination…so the medical associations, association of the biologists, the veterinarians should come together and doing some policy issues governing this [translational study]. I think the policy issue is very important for such activities” (A3, preclinical trial researcher).
Another study participant also stated that:
“…Lack of a clear cut guideline on how to do a clinical trial on traditional medicine is the major challenge because we cannot adopt the guideline for conventional approaches….” (A14, preclinical trial researcher).
Poor research management, including poor financial management or inefficient use of resources and poor quality control, and lack of framed and programmatic research agenda was the other challenges raised to hinder translating animal research into human trials. As stated study participant:
“When you conduct a research it is not only the resources but also research management by itself is a problem. So if you have research funds you get from somewhere else unless there is a smooth research financial management system which motivate the researchers…everybody will lose its hope and their interest in research in the next phase” (A15, clinical trial researcher).
Lack of collaboration
Lack of interdisciplinary collaboration among different professional groups in different institutions at the local and international level, was perceived by respondents to hinder the practice of translating animal research into human trials. Respondents identified a number of features including poor research governance and bureaucracies, minimum preparedness and awareness of the research community, delay in the approval process and communication barriers that hindered effective collaborative working relationships and practices at international level. As stated by the study participant:
“…We need to enhance collaboration with expertise and resources…from outside with certain cautions in terms of not abusing the human trials in general. But the research governance, bureaucracies like delay in the approval process, the preparedness and awareness of the research community, poor facilities and communication are actually hindering in terms of collaboration because many of the collaborators need a kind of swift, smooth…like for instance in terms of the approval process of research protocol, it took like a year in Ethiopia and they don’t want to work with Ethiopian collaborator because of this. So once we can actually improve this research governance and the ethics and regulatory approval process there is also an opportunity just to draw resources from outside so that we can collaborate and hasten product development as well as translate the products into human or animal application” (A10, clinical trial researcher).
Nine participants suggested that translating animal research into human trials needs a multidisciplinary and inter-sectoral collaborative work. Therefore, there should be multi-disciplinary collaboration among biologists, medical professionals, veterinarians, chemists, health officers, policy-makers, social scientists and communities, and companies, which ultimately produce and sell that product to the population. The researchers or professors from basic science or biomedical research area are initiators and part of the whole research process. As noted by the study participant:
“Although researchers are the main actor who come up with the idea and the compound, translational research needs involvement of many actors: the government, biomedical researchers, chemists, physicians, social sciences scientists, nurses, laboratory technicians, immunologists from animals and human side” (A17, preclinical and clinical trial researcher).
Another participant also stated that:
“I think it is a concerted effort. It is not something that is left for one institution, of course the government has given that the mandate for EFDA [Ethiopian Food and Drug Authority] in Ethiopia to regulate and Armauer Hansen Institute to lead clinical trial activities. However, it doesn’t mean that it has to be done there, but…the teaching and research institutions, private and government hospitals, veterinary colleagues and individual scientists should be involved...So that they can work together from animal to human side…that is in terms of doing the study otherwise in terms of stakeholders acting around it, there are a number of different stakeholders we need to have DSMB, IRB approval, investigator team members, monitor, if there is a need for sponsor, if you are soliciting some funding (funder), and CRO. So all those actors need to be there” (A7, preclinical and clinical trial researcher).
Lack of reproducibility of results
Lack of reproducibility of results was also considered as a major bottleneck for translating animal research into human trials. Poor experimental design, poor quality animal experiment, nature of diseases, animal model specifics, differences between animal and human genetic make-up, inappropriate statistical analysis, and anatomical and physiological species difference were seen as contributing factors to lack of reproducibility and replicability of findings in which an agent that is found effective in animal studies might not be effective in human studies. This was only mentioned when the interviewer asked participants in a follow-up question to give reasons for lack of reproducibility. As reported by the interviewee:
“The major bottleneck is the lack of reproducibility and replicability of findings…a drug or vaccine that is found effective in animal studies might not be effective in human studies. It could be because of inappropriate statistical analysis or poor experimental designs. So had the research been designed well it could have an effect in the clinical studies…although the assumption is…that there is…a predictive validity or a face validity between the disease you model on animals and the disease that is in humans…mostly you don’t see the agent be effective in human studies. It could be related the nature of the disease. So in some diseases…you see a positive effect in both studies in another studies you do not see similar findings. So lack of reproducibility is the major challenge in the translating animal research into human trials” (A8, preclinical and clinical trial researcher).
Prolonged ethical and regulatory approval processes
Six interviewees expressed their dissatisfaction in their work in translating animal research into human clinical trials because of the delay and very stringent working environment in ethical and regulatory review and approval processes. The resulting slow and excessively strict ethical and regulatory approval process prevented efficient research conduct.The interviewees mentioned that the time taken for one research protocol to be approved ranged from one to two years. This has contributed a lot in lowering the chance to get external funds for a study or to attract donors and collaborators, because funders or donors are eager to give you the money if you are lagging behind because of the ethical process, unnecessary delay in review process could result in donors losing their interest. Therefore, we have to exploit such opportunities by improving the research process and making ethical and regulatory approval a bit faster. A participant stated that:
“…I do not think that since there is no capacity and experience even ethically they will allow you to translate animal research into human trials,…I was involved in one study which was on edible mushroom…and we proved it in animal that was for liver cancer and the intention was to translate that into human and we did not succeed the level of ethical approval that was needed” (A7, preclinical and clinical trial researcher).
Table 2: Summary of themes emerged as challengesof translating animal research into human trials.
Themes
|
Frequency
|
Sub- themes
|
Frequency
|
1. Lack of finance and
human capacity
|
13
|
√ Lack of funding
√ Limited capacity of researchers (knowledge, skill,
experience, awareness and preparedness), attitudinal problems, lack of physicians’ interest
√ Limited capacity of ethics committee and regulators
in terms of knowledge, skill, experience
|
√ 9
√ 16
√ 2
|
2. Inadequate infrastructure
|
11
|
√ Poor facilities (e.g. accredited laboratories)
√ Shortage of resources
√ Lack of organized center
|
√ 9
√ 5
√ 2
|
3. Operational obstacles and
poor research governance
|
11
|
√ Lack of commitment from researchers, institutions and government
√ Poor research management and quality control
√ Lack of clear policy and guidelines
√ Lack of framed and programmatic research agenda
√ Challenges of logistics and purchasing process
√ Lack of voluntary participation and awareness of patients
|
√ 5
√ 4
√ 3
√ 3
√ 2
√ 2
|
4. Lack of collaboration
|
9
|
√ Lack of inter-disciplinary collaboration
|
√ 9
|
5. Lack of reproducibility of results
|
6
|
√ Anatomical and physiological species differences
√ Lack of animal model genetic make-up specification
√ Pathophysiologic difference of diseases
√ Poor experimental design
√ Poor quality animal experiment
√ Inappropriate statistical analysis
|
√ 2
√ 2
√ 2
√ 2
√ 2
√ 1
|
6. Prolonged ethical and regulatory approval processes
|
6
|
√ Prolonged ethical and regulatory approval processes
|
√ 6
|
Opportunities for translating animal research into human trials
Growing infrastructure and resources
Six interviewees mentioned that these days there are many universities with many postgraduate studies in various disciplines and institutions that are mandated to conduct research, which should be taken as an enabling factor. Since most of the institutions are good in basic sciences if provided special training, they can turn to be efficient in conducting translational research. There are also a motivation and support from Ministry of Innovation and Technology for institutions to be a center for problem solving research rather than a simple office for academic exercise. As the study participant noted:
“…In the Ethiopian context, the two research communities are found either in a research institution or in academic institutions/universities. Now, there is a developing potential, especially in the universities because those universities have science faculties, health colleges, and tertiary hospitals. Therefore, we need to have a somewhat integrated planning so that we can exploit the maximum of the academic community there and then the research idea that can be developed from biomedical field can easily be translated into human or animal testing…” (A10, clinical trial researcher).
According to the interviewees, there are also institutions like CDT-Africa, which provide education, training, and capacity building for researchers to be engaged in translational research and this can be taken as a good start and which can be considered as enabling factor. As stated by the study participant:
“…Institutions like the CDT Africa a world bank initiative dedicated to do this kind of translational study…are enabling environment and now more than ever we have got a wonderful environment to conduct this [translating animal research into human trials]” (A7, preclinical and clinical trial researcher).
The interviewees said that though there are limitations now a day there are growing or better facilities, many tertiary hospitals are now under establishment/ development than previous years. As reported by the study participant:
“I would say at least the experience that I have, at Addis Ababa University; there is phase -1 clinical trials unit, at Armeaur Hansen research institute; there is the whole ward that dedicated for phase- 1 clinical trial unit and internationally accredited laboratory. …These days, there are wonderful infrastructure wise enabling environment” (A7, preclinical and clinical trial researcher).
Five of the interviewees mentioned that the availability of high diversity of medicinal plants, microbes, to some extent availability and use of animal model following proper ethical procedure and large human population in which many of them harboring many infectious and non-infectious diseases could be taken as a big opportunity for translating animal research into human trials. Besides, the existence of multi drug resistance to the drugs being used, inaccessibility of modern medicine to most of the local communities and availability of indigenous knowledge on the use of traditional medicines for curing of diseases is among the enabling factors stated by the interviewees. As noted by the study participants:
“…No full accessibility of modern health cares. So, one approach is to strengthen research on traditional medicine, including the clinical trial because it’s cheap, easily accessible, and it can serve as a means of generating income…” (A14, preclinical trial researcher).
“I think there are…opportunities like the existence of multidrug resistance to the drugs that has been used. So one of the ways forward is to investigate and come up with the new drug to replace those drugs which drug resistance are developed” (A3, preclinical trial researcher).
Four interviewees mentioned that currently, there are opportunities for getting funds at international level and companies are interested to support the initiation of traditional medicine clinical trial. In addition, the Ministry of Innovation and Technology, and Ethiopian Biotechnology Institute are a nowadays giving emphasis on product-oriented research and are allocating better fund as compared to funds made available in the previous years.
“Though competitive there are still research funds to get to clinical trial, so what is expected from us is to write the grant proposal otherwise it may not be as difficult as used to be in the past” (A16, preclinical and clinical trial researcher).
Improved human capacity and better administrative processes
Most interviewees indicated that these days researchers have better capacity in terms of knowledge, skill, training, experiences, and awareness as compared to few years back. Universities have produced higher number of trained researchers and as a result, there is a growing interest of scientists and growing work force in biomedical fields or health related research. In addition, the quality of research now is improving. As noted by the study participants:
“…Opportunity for training, capacity building and education of researchers to be engaged in translational research you can take your clinical trial program offered by CDT-Africa and funded by several projects…. So we can consider these as enabling factors” (A8, preclinical and clinical trial researcher).
“…Well, currently it looks there are a lot of opportunities for clinical trials to be considered we are building the capacity and awareness of health professionals through trainings…on how clinical trial is conducted. So I am sure these days most of them become interested in clinical trials” (A16, preclinical and clinical trial researcher).
Another study participant also noted that:
“Well, I would say the opportunity now is…if you take during my old time it was very difficult, now the attention towards education and research is far better than it used to be in the last two or three decades back” (A15, clinical trial researcher).
Moreover, interviewees mentioned that very recently there are better administrative processes including, supportive rules and regulations, initiations to speed-up ethical and regulatory approval, and the government is giving due attention to problem-solving and product-oriented research. As noted by a study participant:
“…The ethical approval process is being improved…we are working on that how to correct the problem with the ethical committee used to have…even the regulatory approval process…is going to be shorten I believe” (A16, preclinical and clinical trial researcher).
Another study participant stated that;
“The one I would say is there are supportive…rules and regulations issued by the government. …Now the mandate and the proclamation are out there so it is up to the scientist and those other stakeholders to engage” (A7, preclinical and clinical trial researcher).
One respondent also stated, “There are enabling environment that has been worked out which helps if you really want to know the fact that a lot of preclinical study has been done before and having a database on those once, there are some initiatives to develop a database as well. It is something we can also count on experience from other country China, India, Nigeria” (A7, preclinical and clinical trial researcher).
Initiatives for collaboration
Interviewees mentioned that one-health initiative at the national and international level could be considered as an enabling environment and it can facilitate collaboration by creating a platform for experts to meet and work together. As reported by the study participant:
“It is the good way and now we are initiating to work together in collaboration with National Veterinary Institute (NVI), EPHI, AHRI and Ethiopian Biotechnology Institute…to develop a product for human and animal use…because we have to share our expertise or facilities if something that NVI is by far better than others….” (A2, preclinical trial researcher).