clinical research is the type of scientific research that involves human subjects and includes patient - oriented research , epidemiologic and behavioral studies , and outcomes research and health services research .
clinical studies evaluate the effect of interventions or exposures on biomedical or health - related outcomes that include prevention , diagnosis and treatment of diseases .
clinical trials ( cts ) or interventional studies are clinical studies in which participants are assigned by researchers / investigators to receive one or more interventions to assess their safety and efficacy . in observational studies ,
phase 0 studies are exploratory studies involving very limited human exposure to an investigational new drug ( ind ) for example screening studies and microdose studies .
the primary aims of phase 0 studies are identifying , early in the process of drug development , viable candidates and eliminating those lacking promise with a potential reduction in costs and time - to - first - in - human testing .
the endpoints include evaluation of analogs for lead selection , modulation of a molecular target in vivo , whole - body imaging for tissue distribution / target binding affinity , and agent pharmacokinetics [  ] .
phase 1 studies aim to find out the drug s most frequent and serious adverse events and the drug metabolism and excretion .
phase 3 studies gather more information about safety and effectiveness . the randomized controlled trial ( rct )
phase 4 studies occur after marketing approval of a drug by authorities and aim to gather additional information about a drug s safety , efficacy and optimal use .
participation in clinical trials is a voluntary action after subjects are fully informed of the research and give their consent . without participants , no ct can conclude . clinical trial registries ( ctrs )
facilitate the prospective registration of cts and the accessibility of their information by patients , physicians , researchers and other interested stakeholders .
this enhances transparency , increases participation in cts and can eliminate publication bias that arises from publishing positive trial results more than the negative ones , .
some countries mandate ct registration ; others do not ask for registration , but often strongly encourage it .
federal law , declaration of helsinki , european union clinical trials directive , who clinical trials directive , international committee of medical journal editors ( icmje ) .
currently , there are many ctrs with a scale being global ( e.g. who international clinical trials registry platform [ ictrp ] ) , continental / regional ( e.g. eu clinical trials register [ eu - ctr ]   and pan - african clinical trials registry [ pactr ] ) , country - specific ( e.g. us clinicaltrials.gov ) or companies and associations ( e.g. international federation of pharmaceutical manufacturers associations [ ifpma ] ) . clinicaltrials.gov registry ( ctgr ) is a trial registry hosted by the us national institute of health ( nih ) . it is a governmental website . in february 2000 , it was made available to the public as a registry of clinical trials information on federally and privately funded trials conducted under investigational new drug ( ind ) applications to test the effectiveness of experimental drugs for serious or life - threatening diseases or conditions . in september 2008 ,
more information on study participants and a summary of study outcomes , including adverse events were made available . by 17th of march 2014 , ctgr contained 163,090 studies .
the focus then shifted to establishing the two key elements of the platform : the international clinical trials registry platform ( the ictrp network ) and a single point of access ( the ictrp clinical trials search portal ( ctsp ) ) .
ctsp provides a single point of access for the identification of trials in many contributing registries .
ctsp was launched in may 2007 and initially contained trial records provided by three ctrs : the australian new zealand clinical trials registry ( anzctr ) , ctgr and the international standard randomised controlled trial number  ( isrctn ) registry .
in addition to the above registries , the ictrp registry network includes registries based in brazil , china , cuba , eu - ctr , germany , india ( ctri ) , iran , korea , japan , the netherlands , pactr , sri lanka , thai and uk . by 17th of march 2014 , ictrp contained 271,811 records for 229,638 trials . in early 2007 ,
the pan - african clinical trials registry ( pactr ) was established by the south african cochrane centre , in partnership with the european and developing countries clinical trials partnership and the cochrane infectious disease group . in the initial phase , pactr registered trials in hiv / aids , tuberculosis and malaria to demonstrate proof of concept . once established , the goal of pactr is to become the registry of choice for any clinical trial conducted in africa . on 25th of september 2009 ,
pactr was officially launched as a member of the who primary registry network in abuja , nigeria .
pactr is presently the only african member of the who network of primary registers and transfers all trial information to the who ctsp on a quarterly basis . as of 17th of march 2014
the aim of this work is to study the profile of clinical trials in egypt in three clinical trial registries with different scopes : the global ictrp registry , the regional / continental pactr registry and the us ctgr .
the us clinical trial registry  clinicaltrials.gov ; ctgr  was searched for trials conducted in egypt . in the  advanced search http://clinicaltrials.gov/ct2/search/advanced ,
 egypt  was searched in the countries 1 , 2 and 3 and the search yielded 548 entries .
clinical trials search portal ( ctsp ) ( http://apps.who.int/trialsearch/advsearch.aspx ) was searched for trials from egypt and the search yielded 686 entries .
the pan - african clinical trials registry  pactr  ( http://www.pactr.org/ ) in the advanced search and 73 entries for 56 studies were retrieved .
all searches were done on the same day ( 10th of march , 2014 ) .
the ictrp was selected because it is an international registry that accepts studies from several registries including country - specific , regional and continental ones .
the clinicaltrials.gov was chosen because it is the most mature registry and it preceded the ictrp and thus it may contain studies not listed in the latter registry . the pactr was chosen because it is the only registry in the continent where egypt lies ( africa ) . studying this latter registry
as of 10th march 2014 , the total numbers of studies included in the ictrp , ctgr and pactrp were 229,638 , 163,090 and 645 , respectively . within ictrp ,
egypt ranked the 55th with a total of 686 studies representing 0.30% of ictrp total . within ctgr ,
egypt ranked the 115th with a total of 548 studies representing 0.34% of its total . within pactrp ,
egypt ranked the 2nd ( following south africa ) with a total of 73 entries for 56 studies representing 11.3% of pactrp total ( table 1 ) .
ctgr and pactrp are primary registries that receive data directly from registerers while ictrp receives trial information from many primary registries .
main sources of egypt s studies in ictrp were ctgr ( 72.3% ) , anzctr ( 13.6% ) , eu - ctr ( 7.7% ) , isrctn ( 4.2% ) and ctri ( 2% ) . comparing study titles
registration of egypt s clinical studies to both ctgr and ictrp started in 1999 and peaked in 2012 ( fig . 1 , fig .
active recruiting status was encountered in 27.4% in ctgr , 19.1% in ictrp and 26% in pacrp .
completed status was encountered in 53.8% in ctgr and 33.9% in pactrp and not mentioned in ictrp .
study results were only available in ctgr and only 8% of egypt s studies have results ( table 1 ) . in pactrp and ctgr ,
most studies were sponsored by universities / organizations followed by industry in ctgr or individual researcher in pactrp .
the most common egyptian sites were cairo university , mansura university , ain shams university , assiut university and alexandria university ( fig .
the most common industrial sponsors were novartis , hoffman - la roche , sanofi , pfizer , eli lilly and bayer ( fig .
interventional studies were the most common type of studies in both ctgr and ictrp ( 84% ) followed by observational studies .
treatment was the most common study purpose ( 69% ) in ctgr and pactrp followed by prevention ( table 2 ) .
in ctgr , combined safety / efficacy was the commonest endpoint ( 49.1% ) followed by efficacy alone ( 19.5% ) .
in the three registries , inclusion of both genders and adults was the most common practice .
the median number of enrolled subjects was 155 in ctgr , 150 in ictrp and 63 in pactrp .
for interventional studies in ctgr and pactrp , the most common intervention was drug use ( 61.9% ) followed by procedure ( 12.8% ) .
in the three registries , the commonest study phase was phase 3 followed by phase 4 and phase 2 ( table 3 ) .
the commonest allocation method was the randomized method ; blinding was implemented in many of trials and was mostly double - blind . in ctgr and ictrp ,
observational studies constituted almost 15% of the studies and were mostly prospective and cohort studies ( table 4 ) .
the most researched conditions were digestive system diseases , cancers / other neoplasms , symptoms / general pathology ( fig .
the most common conditions were cancer , hepatitis and diabetes mellitus ( fig . 6 ) .
in pactrp , diseases and conditions being researched were listed as individual conditions rather than grouped items . in pactrp ,
pregnancy and infertility were the commonest conditions ( n  =  12 ; 21.4% ) followed by surgical procedure ( n  =  9 ; 16.1% ) , cancer ( 12.5% ) , pains ( 10.7% ) , and others ( 39.3% ) .
egypt is the  land of civilizations  and is reputed worldwide for its distinct 7000-year - old record of civilization and immense wealth of knowledge .
he performed surgery , practiced some dentistry , extracted medicine from plants and knew the position and function of the vital organs .
surgical instruments and surgical procedures such as circumcision are documented on the paintings on the temples , . with its 82-million population ,
however , it contributes only 0.34% of records in us clinical trial registry ( clinicaltrials.gov ; ctgr ) and 0.30% in the who registry ( ictrp ) .
there are 24 faculties of medicine with up to 34 departments in each faculty , 18 faculties of dentistry with up to 12 departments in each faculty , 34 faculties of pharmacy with up to 9 departments in each faculty , 12 faculties of nursing with up to 7 departments in each faculty   and 6 faculties of physical therapy with up to 8 departments in each faculty . in egypt , there are more than 42,000 faculty members and 344,000 post - graduate students , , 140,000 physicians , 18,200 dentists , 37,500 pharmacists 176,000 nurses and 35,000 physical therapists .
clinical research including clinical trials is an essential mandate for getting master and doctorate degrees .
thus , the output of about 94 health - related faculties , 1400 departments and the huge number of health care professionals and faculty members is definitely more than the registered studies .
the apparent low contribution of egypt in trial registries may be related to multiple factors .
there is no egyptian national trial registry that hosts all trials running in the country .
many trials are not recorded in trial registries whether global e.g. who ictrp , regional / continental e.g. pactrp or other e.g. ctgr .
. the reasons why some egyptian trials are registered can be imputed from examining the trial sponsorship where most trials are sponsored by either pharmaceutical industry or academic universities .
many of the pharmaceutical industrial sponsors include an egyptian site in addition to other non - egyptian sites .
in addition to innovation , great majority of research conducted in the egyptian universities aims at publication in renowned international journals that both increases author citation h - index   and advances the university ranking in the university index , .
based on icmje , most renowned journals ask author to provide details for trial registration prior to publication . otherwise , many egyptian investigators may be unaware of the presence of trial registries or the mandate of registration
they may miss the support from administrative research offices / facilities that can carry out this job on their behalf .
of the three studies registries , the most mature registry is ctgr followed by the ictrp and
there are many similarities between search fields in the three registries ( table 5 ) .
ctgr allows searching by intervention , study phase , gender , age groups , date of last update , sponsors / collaborators , results , completion status .
it displays the total number of studies and allows further work on the results within the website .
pactrp allows further search by study purpose , dates of start and end and principle investigator name and country . however , interface was less user - friendly and total results are not shown and could not be worked within the website .
the most common diseases researched in the registries were digestive system diseases , cancers / neoplasms , hepatitis , dm and urogenital conditions . while most of these conditions are included in the top egyptian biomedical research topics , yet
similarly , tumors were the 7th research priority but came first in the registered trials .
reasons for the difference between the country s research priorities and the actual research done can be many
universities are not under the portage of the ministry of health ( moh ) and thus are not mandated to comply with its set priorities .
industry enforces research topics that are within their main interest e.g. to get a drug s approval .
additionally and as mentioned above , trials in the registries do not provide a comprehensive picture of the biomedical research in egypt .
most of the studies were funded by either academic universities / organizations ( 3854% ) or industry ( 3843% ) and most of the industries are multinational ones .
unfortunately , we could not get information on the amount of funding and the share of different stakeholders .
in developed countries such as us , investment in health research comes mainly from industry ( 64.4% ) , federal government ( 32.6% ) and universities ( 3.0% ) .
industry focuses on research with the best return on investment ( roi ) . this may , or may not , coincide with the national priorities .
thus , in developing countries such as egypt , governmental sponsorship should predominate to enforce the national priorities . while the mentioned registries were set to host clinical trials , yet up to 17% of the entries refer to observational studies i.e. non - trial studies . with time , the number of observational studies in clinicaltirals.gov increased and the scope of registration widened .
for example , the clinicaltrials.gov was initially set to host clinical trials on ind for life - threatening conditions , then it expanded to include other types of studies as well as their results .
this was because much of the rationale for the prospective registration of clinical trials applies to the registration of observational studies .
observational studies could provide valuable information not achieved even by the well conducted phase iii clinical trials particularly related to drug safety .
making both observational and interventional studies available in a single registry will provide researchers and others with a more comprehensive view of the growing evidence base [ http://www.ncbi.nlm.nih.gov/pmc/articles/pmc2952011/#!po=10.7143 ] .
however , this relates to the source registries and the way they were designed ( table 5 ) . for example , some registries ask specifically for some information not requested by the others making comparison unfeasible .
also , some of the information requested may be either optional or may not have exhaustive quality checks for what was entered .
even , if some data were entered there were no exhaustive checks that read , understand and advise authors for the necessary changes .
. however , clinical trials from egypt in three trial registries are apparently low and do not accurately reflect clinical research conducted in egypt or its potential .
we recommend that egyptian authorities immediately start a national egyptian clinical research registry ( egcrr ) that matches the well - developed registries particularly ctgr and hosts clinical trials as well as observational studies ( table 5 ) .
we propose that egcrr be hosted by the egyptian ministry of health , the ministry of higher education or the ministry of scientific research .
we recommend that all egyptian clinical research mandatorily get registered to this egcrr immediately following ethical approval or exemption by the ethical committees , and that investigators and institutions receive appropriate training on research registration .
in addition to the several advantages of registration e.g. transparency , enhanced participation and bias elimination , such egyptian registry ( egcrr ) would ensure that research is not repeated and that the country s research activity can be assessed at any time . to ensure compliance with registration
this can be done at least at two levels ; first funding may be linked to registration and second there should be some legislation to mandate registration .
we are to see the first egyptian clinical research law that will regulate and advances clinical research as well as protect research participants rights , safety and well - being .
this law should address registration . to protect the interests of sponsors and investigators , they are highly encouraged to patent and copy - right their investigational agents and intellectual work prior to embarking on experimentation in humans and hence registration
. the registry should not reveal the sensitive and secret aspects of an investigational agent e.g. its chemical structure .
we also recommend setting of research support offices / facilities that can carry out the job of registration or at least provide the support and guidance .
it is highly recommended that egypt sets a clear and frequently updates national research priorities .
these priorities should be decided on with the involvement of all stakeholders including , but not limited to , moh , academic institutions , politicians , researchers , funding agencies , pharmaceutical companies and community representatives .
research funding should be linked to compliance with these priorities . to avoid skewing research toward the best interest of international pharmaceutical industry , governmental funding of research
 registering clinical trials ( cts ) in public domains enhances transparency , increases trust in research , improves participation and safeguards against publication bias . 
 this work was done to study the profile of clinical research in egypt in three ct registries with different scopes : the who international ct registry platform ( ictrp ) , the continental pan - african ct registry ( pactr ) and the us clinicaltrials.gov ( ctgr ) . in march 2014 , 
 ictrp , pactr and ctgr were searched for clinical studies conducted in egypt . 
 it was found that the number of studies conducted in egypt ( percentage ) was 686 ( 0.30% ) in ictrp , 56 ( 11.3% ) in pactr and 548 ( 0.34% ) in ctgr . 
 most studies were performed in universities and sponsored by university / organization , industry or individual researchers . 
 inclusion of adults from both genders predominated . 
 the median number of participants per study in the three registries ranged between 63 and 155 . 
 the conditions researched differed among the three registries and study purpose was mostly treatment followed by prevention . 
 endpoints were mostly efficacy followed by safety . 
 observational : interventional studies ( i.e. clinical trials ) represented 15.5%:84.5% in ictrp , 0%:100% in pactr and 16.4%:83.6% in ctgr . 
 most interventions were drugs or procedures . 
 observational studies were mostly prospective and cohort studies . 
 most cts were phase 3 and tested drugs or procedures . 
 parallel group assignment and random allocation predominated . 
 blinding was implemented in many of trials and was mostly double - blind . 
 we conclude that cts from egypt in trial registries are apparently low and do not accurately reflect clinical research conducted in egypt or its potential . 
 development of an egyptian ct registry is eagerly needed . 
 registering all egyptian cts in public domains is highly recommended . 
Introduction
Methods
Results
Discussion
Conclusions
Recommendations
Conflict of Interest
Compliance with Ethics Requirements