Clinical Drug Trials in Ukraine: Myths and Realities

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ResearchonClinicalTrials
ClinicalDrugTrialsinUkraine:Mythsand
Realities
©BerneDeclaration,September2013
ClinicalTrialsinUkraine
2
TheBerneDeclaration
Foundedin1968,theBerneDeclaration(BD)isanindependentnon‐governmentalorganisationformedtocombattheroot
causesofpovertybypromotingmoreequitableandsustainablerelationsbetweenSwitzerlandandthedevelopingworld.We
are committed to global justice and address issues of trade policy, commodity production and trade, the politics of food,
finance, fair trade and health. As part of a worldwide network of human rights groups, environmental and development
organisations, the BD promotes a more equitable and humane route to global development. To this end, we carry out
investigativeresearch,runpubliccampaignstoraiseawarenessandundertakesuccessfuladvocacyworkinSwitzerlandand
oninternationalstage.
Moreinformationonwww.ladb.ch
BerneDeclaration
Av.Charles‐Dickens4,CH‐1006Lausanne
Tel.:+41216200303–Fax:+41216200300
[email protected],www.ladb.ch
IMPRESSUM
Reference:
BerneDeclaration(Ed.),ClinicalDrugTrialsinUkraine:MythsandRealities.Lausanne/Zurich
(2013).
©KEYSTONE–MichaelKupferschmidt
Photoonfirstpage:
[email protected]
©BerneDeclaration,September2013
ClinicalTrialsinUkraine
3
Listofabbreviations
4
Somebackgroundinformation
5
Mythnumber1:Clinicaltrialsareanopenbusiness
6
Mythnumber2:ClinicaltrialscomplywithUkrainianlegislation
8
2.1.RecentcontroversiesinUkrainianclinicaltrialsinvolvingchildren
8
2.2.Theproblematicdoctor‐patientrelationship
13
Mythnumber3:Clinicaltrialsitesmeetinternationalstandards.
15
Mythnumber4:CTsinUkraineareunbiased
17
Mythnumber5:SponsoringcompaniesareintotalcontrolofCTs
18
Mythnumber6:IndependentethicalcontrolofCTsisguaranteed
20
Conclusion
23
Annex:listofinterviews
24
For strategic reasons and to maximise profits, industry‐sponsored clinical drug trials on human subjects are increasingly
offshored in developing and emerging countries. In those countries, pharmaceutical companies can find a large pool of
vulnerable people willing to take part in drug trials as it represents often their only treatment option. In addition, weak
regulatory environments enable the pharmaceutical multinationals to shorten clinical trials duration. This increases
significantly the risk of ethical violations. Concerned about this situation, the Berne Declaration launched several
investigationsin2012and2013.FourfieldstudiestookplaceinArgentina,India,RussiaandUkrainetobetterunderstand
these contexts in which numerous clinical trials take place. How is the regulatory system performing? Are the ethical
standardsrespected?HowdoSwissfirmsconductingclinicaltrialsbehaveinthesecountries?Aresearchwasalsocarriedout
inSwitzerlandtounderstandhowSwissmedic–theSwissmedicinesagency–functionsandcarriesouttheethicalcontrolof
clinicaltrialsthatwereconductedinthirdcountries.ThefieldstudiesweredonebyinvestigativejournalistsandbyanNGO
specialisedinthefield.Thefivei[email protected]ladb.ch.
ThisreportisbasedontheresearchdonebyaUkrainianinvestigativejournalist.
©BerneDeclaration,September2013
ClinicalTrialsinUkraine
Listofabbreviations
CRO
CT
EBA
FDA
LEC
MoH
SEC
ContractResearchOrganisation
Clinicaltrial
EuropeanBusinessAssociation
Food&DrugAdministration
LocalEthicsCommittee
MinistryofHealth
StateExpertCentre
©BerneDeclaration,September2013
4
ClinicalTrialsinUkraine
5
Somebackgroundinformation
Thefirstauthorisationtoconductaninternationalclinical
drug trial in Ukraine dates back to 1996. The State Expert
Centre (SEC) of the Ministry of Health1 reviews and
regulatesallclinicaltrials(CTs)inthecountry.
Since 1996, the number of multicentre international CTs
hasbeenconstantlygrowinginUkraine,accordingtoofficial
figures. Whereas in 1998 20 international CTs were
conducted in the country, the number reached 466 CTs in
20082. According to one Contract research organisation
(CRO), more than 500 CTs were initiated in 2011 alone in
Ukraine, suggesting an upward trend3. The number of
approvedCTsiteshasfollowedasimilartrend,from175in
2001tomorethan1300in2009.
Other figures – including statistics on the type of trials
being conducted by December 2012 – can be found in the
ScripUkrainecountryprofile4.
ThemajorityofCTsinUkrainearePhaseIIItrials(66%of
all CTs in Ukraine in 2006), followed by Phase II trials
(30%) and a minority of Phase I and IV trials (1% and 3%
respectively)5.
Recent amendments in the legislation have tried to bring
the regulatory environment in Ukraine in conformity with
the one of the European Union. The most important
legislativeordersforthosewhoconductCTsinUkraineare:
©BerneDeclaration,September2013


MOHofUkraine23.09.2009№690"OnApprovalofthe
ProcedureforConductingClinicalTrialsofMedicinal
ProductsandExpertEvaluationofMaterialsPertinent
toClinicalTrialsandModelRegulationsoftheEthics
Committee."(AmendedbyDecreeofMinistryofHealth
of12.07.2012№523)
MOHofUkraineof11.04.2012№255"Onregulating
theethicalaspectsofclinicaltrialsofmedicinal
products"6
Despitethefactthatmanyactorsinvolvedinclinicaltrials
depict the Ukrainian regulatory environment as quite
favourable,wehavecomeacrossmanyproblemsandissues
related to the conduct of clinical trials during our
investigations. Through interviews with officials,
researchers and participants involved in CTs, through
analysis of statistics, speeches and statements made by
representatives of the medical community and
pharmaceuticalcompanies,throughexchangeswithvarious
actors and through monitoring of media reports, our
investigatorhas gathered elements that dispel some myths
surroundingclinicaltrialsinUkraine.
ClinicalTrialsinUkraine
6
Mythnumber1:Clinicaltrialsareanopenbusiness
Clinicaldrugtrials(CTs)areoneofthemostrestrictedand
secretive areas of medicine. Despite the fact that CTs were
first conducted over 15 years ago in Ukraine, information
about them is extremely scarce and difficult to find. The
organisers of CTs usually refer to medical confidentiality
and the desire of pharmaceutical companies to maintain
tradesecrets.
At all scientific conferences, in congresses, in interviews
and in official statements, CT organisers – including
sponsoringcompanies,officialsfromtheMinistryofHealth,
and medical researchers – state the following: CTs in
Ukraineareconductedunderstrictgovernmentalcontrol,in
strict accordance with the standards and regulations of
Ukraine. CTs bring huge benefits to patients and to
volunteers who participate in clinical trials. Medical
institutions gain access to the latest information and
technology;CTsthuspavethewayforprogressinmedicine.
Severallegislativechangeswererecentlymadeinorderto
bringtheregulationofclinicaltrialsinUkraineinlinewith
internationalstandards7.
What really happens? Does society have access to
information on CTs? Does society have the right to know
andtoscrutinisecompliancewithCTregulations?Arethere
violationsoftherightsofCTpatient‐participants?
First of all, it should be said that freedom of speech in
Ukraine is restricted and limited in comparison with West
European countries8. Very little information on CTs can be
found in the public domain and in local medical literature.
When a journalist tries to investigate the subject, he/she
faces many hindrances and difficulties as he/she searches
forinformation.Ingeneral,ontherequestofajournalist,a
governmentagencyshouldrespondwithin5days.However,
bylaw,ifanissueisrathercomplex,areplymaybegivenin
30days,orevenlonger.Governmentofficialsoftenusethe
maximumterm.Onceareplyisgiven,itdoesnotrespondto
the questions raised, but gives a general outline on how
plansandprogrammesarecarriedout,etc.InUkrainethisis
calleda“formalreply”,withouttherequestedcontent.Most
journalists are not interested in investigating the topic of
clinicaltrials,becauseitmaytakemorethanamonth,evena
year, to gather information. And once the official “formal
replies”areobtained,itoftenappearsthatthereisnothing
to write about. If critical articles are published on certain
topics, officials go to great lengths to prove that they are
actingentirelyaccordingtotheletterofthelaw.
Numerousformalinterviewsandconversations9–mostof
whichwerenotrecorded,asotherwisethepersonwasnot
willing to talk – show that all key stakeholders in the
organisationofCTsarereluctanttoanswerquestionsabout
©BerneDeclaration,September2013
them. These include pharmaceutical companies (sponsors),
organisations that conduct CTs on their behalf (contract
research organisations or CROs), managers of medical
facilities,universitiesordepartments(sites)whereCTstake
place,aswellasthepersonnelthatperformthem.Alltheir
answersarelimitedtostatingthatCTsareheldforthesake
ofthepatients,whoarenowbenefitingfromnewdrugsthat
will save the health and lives of millions of people in the
future. No one wants to go into details. One of the
advantagesputforwardbythemisthefactthatduringCTs
notonlytheefficacybutalsothesideeffects(safety)ofnew
drugs can be tested. These can thus be eliminated in the
drugdevelopmentprocessbeforetheyarecommercialised.
All in all, any information related to clinical trials is
considered strictly confidential by physicians and officials.
They refuse to provide information, explaining, firstly, that
their patients have not given their consent, and secondly,
that their sponsors do not allow the disclosure of
confidentialbusinessinformation.Noneoftheinterlocutors
agreed to provide us with the informational consent form
thatshouldbestudiedandsignedbyaCTparticipant.
Several discussions were also held with the companies
Roche and Pfizer (at the European Business Association,
EBA)10.Theypromisedtotakeuptheissuewiththeirhead
office. Finally, a refusal to share documents such as the
consentformwasonceagainissuedonthegroundsthatthe
pharmaceutical companies fear that their competitors
wouldreceivetheinformationsupplied.
A similar situation arose with regard to contacting CT
patient‐participants.DuringaninterviewattheEBA,several
attempts were made to arrange a meeting with a principal
investigator and patients. The request was denied on the
grounds that it violates the rights of the patients and the
“Law on the Protection of Personal Data”. The request to
communicate with CT participants, at least on the phone,
was also rejected, even when offered to interview them in
thepresenceoftheirphysician.
Rocheprovidedcontactdetailsofaphysicianwhoagreed
to answer questions. Despite all requests the physician did
notgiveasingleopportunitytomeetortalkoverthephone
withpatientsthathaveparticipatedinCTs.
Freedom of speech in Ukraine is limited. Journalists’
requests are often ignored or receive a formal response.
Anothermethodofgatheringinformationwastriedthrough
NGOs that protect the rights of patients. V. Serdyuk, the
president of the Ukrainian Council for Patients’ Rights and
Safety, agreed to assist. He used his position as a
representativeofthepatients’organisationandheldseveral
meetingswithofficialsfromtheMinistryofHealthandother
stakeholderstogatherinformationaboutCTs.
ClinicalTrialsinUkraine
7
Since 10 January, when the New Year holidays ended in
Ukraine,wehavebeenactivelyworkingwithV.Serdyukto
gain access to clinical sites and to meet CT participants.
Being a journalist, our investigator was refused access.
However,thepresidentofthepatients’organisationdidnot
achieveanythingeither.AttheMinistryofHealthandatthe
MoHStateExpertCentre,hewaspromisedthemeetings,but
theywereputoffuntil“tomorrow”andnevertookplace.He
talkedaboutthisinhisinterview.
committee hadnotyetbeensetup.Firstly,it isimpossible
to carry out CTs without an LEC. Secondly, almost 10
monthshadpassedsincethedissolutionoftheMoHCentral
EthicsCommittee.Inthisperiod,everyhospitalshouldhave
set up an LEC and held regular meetings. There had not
beenasinglemeetingattheregionalhospital!
J: According to the law, many situations that arise
during CTs are required to be resolved in a week. For
example, if a patient‐participant in a CT suffers from
side effects, a prompt decision must be made as to
whether or not he/she should be taken out of the CT.
Therearemanysimilarsituationsin whichadecision
hastobemadenotbyaphysician,butbytheLEC.
V.S: It was not possible to get answers from the LEC
chairman.Hepromisedtofindtimeforameeting,butthen
suddenly backtracked. Later on, he said on the telephone
thatatfirsthehadmadeamistake:thatthecommitteehad
beensetupandthatminutesoftheLECmeetingsdidexist.
He promised to show me the document, but then stopped
answeringhistelephone.
InterviewwithViktorSerdyuk,presidentoftheAll‐
UkrainianCouncilforPatients’RightsandSafety
Journalist:Asadefenderofpatients’rightsdoyouhave
therighttogotoanyhospitalandtalktopeople?
V.Serdyuk:YesIdo.Itisallowedbylawanditislaiddown
in the charter of our organisation. However, the hospitals’
rules are the following: without the permission of a chief
physician the medical staff will not answer any questions,
especiallyquestionsaboutCTpatient‐participants.
J: Due to the nature of your job, you are acquainted
with many hospital chiefs. Why did you not apply to
them?
V.S:Achiefphysicianofahospitalwillanswermyquestions
onlyafterhehasbeenallowedtodosobytheofficialsofthe
corresponding department of the MoH. At the Ministry I
was not refused, but I only received promises. My
appointments, however, were always postponed
indefinitely.
Finally,mypatienceranoutandIwenttotheKievRegional
Hospital, which is in the list of CT sites, without calling in
advance to make an appointment. A chief physician was
forcedtomeetmebecauseIwasaskingabouttheactivities
of the Local Ethics Committee (LEC). This is an important
question, and he could not refuse to give me the
information.Thechiefphysiciancalledforthephysicianin
chargeoftheLEC.DuringaconversationwiththeLEChead
itturnedoutthatnomeetingshadbeenheldandthatthe
©BerneDeclaration,September2013
Informationgatheringhasbecomemoredifficultafterthe
CT scandals broke in Kiev and Poltava (see chapter 2).
Officials, physicians and representatives of pharmaceutical
companies refused to meet or talk in March. We thought
that the CT scandal involving children would soon be
forgotten, and that it would be easier to obtain the
necessary information. However, a new scandal broke, the
epicentre of which was the Kiev Psychiatric Hospital. This
time it was not about CTs – although this institution does
also conduct CTs, including trials sponsored by Swiss
pharmaceuticalcompanies11–butabouttherulesthatapply
tophysicianstreatingpatients(see2.2).
ClinicalTrialsinUkraine
8
Mythnumber2:ClinicaltrialscomplywithUkrainianlegislation
2.1.RecentcontroversiesinUkrainianclinicaltrials
involvingchildren
In early March 2013, a CT controversy broke out in
Ukraine. It was the first time such a “scandal” had been
discussedinpublicsinceourinvestigatorhasbeenworking
ontheCTissue–thatis,formanyyears.Monitoringofthe
media reports showed that many journalists did not pay
close attention to the details and did not elaborate further
ontheissue.Itwasdifficultforthemtounderstandthekind
ofviolationsthathadoccurredasnoonereadsorknowsthe
laws, given the scarcity of publicly available information
aboutCTs.
ItallbeganwithastatementmadeinearlyMarch2013by
Valery Golovko, a deputy from the opposition party
“Batjkivshyna”(“Fatherland”),attheParliamentofUkraine.
Accordingtomediareports12,hestatedthatamedicinehad
been tested at the regional hospital of Poltava incurring
numerous violations, including the fact that the trial had
been carried out on orphan children without due informed
consentandthatthehospitaldidnothavetheaccreditation
certificatenecessaryforconductingsuchstudies.
Later on, 14 deputies from various opposition parties
releasedajointstatementindicatingthatviolationsindrug
trials in which children, including orphans, were involved,
occurrednotonlyinPoltava,butalsoinKiev.Theyaccused
the Ministry of Health of Ukraine of covering up unlawful
practicesinclinicaldrugtrialsinvolvingchildren,basedon
whattheycall“numerousfacts”13.Thesetrialsinvolvedthe
followingmedicinesatdifferentlocations:

Doripenem (Doribax®), a broad‐spectrum
antibiotic used to treat complicated urinary tract
orintra‐abdominalinfections,marketedbytheUK
companyJanssen‐Cilag(asubsidiaryofJohnson&
Johnson).TheCTunderinvestigationtookplaceat
thePoltavaOblastChildren’sHospital.

Bosentan (Tracleer®), used in the treatment of
pulmonaryarteryhypertension(PAH),licensedby
the Swiss company Actelion Pharmaceuticals. The
CT under investigation took place at the Medical
Centre of Paediatric Cardiology and Cardiac
SurgeryinKiev.

Somatropin (Jintropin®), a synthetic hormone
used to treat Growth Hormone Deficiency,
produced by the Chinese company GeneScience
Pharmaceuticals. The CT under investigation took
place at the Institute of Endocrinology and
Metabolism – Academy of Medical Sciences of the
UkraineinKiev.
©BerneDeclaration,September2013
DeputiesinUkrainehaveparliamentaryimmunity,i.e.they
cannot be prosecuted for their actions, speeches and
statements. They can only be brought to trial for criminal
cases in which they are directly involved. Therefore, the
deputiesmaynotonlyreceiveandexamineanydocuments,
but also disclose violations, report cases of corruption,
breaches of law, etc. The deputies handed their statement
aboutCTstotheGeneralProsecutorofUkraine.
Following the deputies’ statement, the Ministry of Health
(MoH) issued a formal press release announcing that a
request for clarification had been made to the accused
institutions and that, after receiving their replies and after
verification of all the relevant documentation, the
allegations were proven to be unfounded, since all the
clinicaltrialswerecarriedoutinaccordancewithUkrainian
regulations.Additionally,itstatesthat
“havingconsideredtheinformationonviolations
atCTs,theMinistryofHealthwillsetupaspecial
commissiontoexaminetheproceduresofclinical
trials in accordance with MoH Ukraine Order
number 690. Results of the examination will be
madepublic”14.
The Ministry of Health has also announced that, after
studying the case, it reserves the right to file a legal action
against the deputies should it be proven that they have
spreadfalseinformation.
Since that press release, more than two months have
passed. The Ministry of Health has not yet reported the
results of the commission’s work, which was supposed to
study the issue of clinical trials involving children. It is not
known whether such a commission has been formed and
whichexpertshavebeeninvolved.
2.1.1. AnalysisofActelion’sbosentanclinicaltrial
TheMoHpressreleasementionedthefollowingaboutthis
case:
“Research into the drug “bosentan” was
conducted withthe participation of one child at
the Scientific and Applied Medical Centre of
Paediatric Cardiology and Cardiac Surgery of
MoH Ukraine in Kiev. The clinical trial was
approved at a meeting of the Scientific Expert
Council of the State Expert Centre of MoH
Ukraine (Minutes Item 01 dated 27.01.2011). A
confidential official letter was sent to the Office
oftheVinnytsyaCityCouncilChildCareServices
toinformthemthatthepatientwastakingpart
ClinicalTrialsinUkraine
in the clinical trial. The clinical trial
accreditation certificate was available at the
hospital”15.
The statement made by the group of opposition deputies,
however,saysthefollowing:
“In the Department of Paediatric Cardiology of
the Scientific and Applied Medical Centre of
Paediatric Cardiology and Cardiac Surgery of
MoH Ukraine, cases were found during research
on the drug “bosentan” in which the Child Care
Services had not been informed about the fact
that children were taking part in the clinical
trial.Theclinicaltrialswereconductedwithouta
proper accreditation certificate from the health
institution”16.
MentionoftheChildCareServices17inthepressreleaseof
the MoH is evidence that an orphan child was not only
under treatment, but took part in a CT. Usually the Child
CareServicesshouldonlybeinformedwhenachilddoesnot
have one or both parents. If a child has both parents, they
are asked to sign an informed consent form. As a rule,
medical researchers do not report such cases to any
institution, especially the guardianship services, as they
havenothingtodowithit.Butifanorphanorsemi‐orphan
childisinvolvedinaclinicaltrial,asocialserviceofficialor
the director of the corresponding orphanage must sign the
relevant documents and take responsibility for the
consequences. According to key informants, signing an
informedconsentformforanorphantotakepartinclinical
trials is a mere formality and it is easy to obtain from an
officialorthedirectorofanorphanage18.
Bylaw,theguardianshipservicesdonothaveanyleverage
overthehospital.Thereisnoavailableinformationshowing
that the guardianship services have ever intervened in the
process of administering treatment to children, and the
same is true of clinical trials involving children. By law,
Child Care Services must make sure that the rights of
children living without their parents are not violated.
However, not a single case has been reported in which the
Child Care Services monitored how orphans were treated
and how clinical trials involving these children were
conducted.Itseemseverythingisinthehandsofphysician‐
researchers.
The fact that the Child Care Services in Vinnytsya were
contactedindicatesthatthechildlivedinthiscityandthat
he/shewasanorphan.
Ukraine has long rejected proposals to conduct clinical
trials involving children19. Two years ago, amendments
weremadetolegislationandCToperatorsarenowallowed
©BerneDeclaration,September2013
9
to involve child participants in CTs. However, the law
permits the participation of orphans in CTs only in very
exceptionalcases,whentheproductisvitaltothechildand
can save his or her life. On the question of benefit‐harm
assessmentthereshouldbeabsolutelynodoubtthattheCT
will benefit the child’s health. In this way, the law is
intendedtoprotecttherightsofchildrenwhoseparentsare
nolongertheretodoso.
AnotherpointintheMoHstatementraisesquestions:the
factthatonlyonechildwasinvolvedinthetrial.Conducting
aCTononlyoneparticipantseemsinefficientandpointless.
However, pulmonary artery hypertension (PAH) is a rare
disease. According to a recent search of an international
database20, 104 studies on bosentan are listed, of which 2
areactiveinUkraineattheaforementionedinstituteinKiev,
and are sponsored by Actelion. Both are Phase III
international trials studying PAH in children, one being an
extension of the other. A total number of 64 children have
been enrolled, spread over 48 trial sites located in 19
countries (including 3 sites in Ukraine). It may well be,
therefore, that only one child has participated in the
controversial trial – but this kind of information is not
availablefromthedatabaserecord.
Anothertroublingfactisthatthepaediatricformulationof
bosentanisnotallowedintheUnitedStates,whereasithas
been authorised in the European Union (July 2009) and in
Switzerland (July 2010), although in the latter case only
implicitly. The FDA medication guide for bosentan, which
was revised in October 2012, says: “It is not known if
Tracleer is safe and works in children below 12 years of
age”21.Whetherthistrialwasintendedtofurtherdocument
the efficacy and safety of the paediatric formulation of
bosentan in order for it to be re‐submitted to the FDA, or
whether the organisers took an excessive risk involving
childrentotestthisdrug,includinginUkraine,isnotclear.
Intheirstatement,thedeputiessuggestthatnotonlyone
butseveralchildrenparticipatedintheUkrainianbosentan
trial. This is also disturbing. However, it will be difficult to
find compromising evidence from the Ukrainian records, if
any.Sincethetrialstartedin2011,theclinicalrecordscould
easilyhavebeenfiledawayandsubsequentlychanged,asis
customary in Ukraine. At the 4th Ukrainian Pharmaceutical
Forum, which took place in Kiev in October 2011,
representatives of Local Ethics Committees proposed that
CT documents should be stored for 10‐15 years. However,
hospitals do not have the facilities for storing a large
numberofdocumentsovertheyears.Itwasdifficulttoget
an answer to questions regarding where and how these
documents are stored. This clearly suggests that CT
documentsarenotproperlystored.Thereareallegedcases
in which a patient’s medical record has been rewritten,
eitherinitsentiretyoronafewselectedpages,inorderto
ClinicalTrialsinUkraine
hidephysicians’mistakes.Therefore,theCTdocumentsfor
2011mayhavebeenthrownawayorrewrittenasneeded.
Finally, the fact that the deputies alleged that the
institution where the trial took place had no due
authorisationtodosoisalsoaconcern.
2.1.2. AnalysisoftheJintropintrial
The second allegedly unethical trial took place at the
children’sdepartmentoftheInstituteofEndocrinologyand
MetabolisminKiev.
Accordingtothedeputies,theCTunderinvestigationwas
violatingthelaw.Hereistheirstatement22:
“In the Paediatric Endocrinology Department of
the Public Institute of Endocrinology and
Metabolism, 26 patients have participated in a
clinical trial of the Chinese drug “Jintropin”
beyond the period specified by the insurance
contract.Theinformationconsentproceduresof
9 patients were contrary to the requirements of
thelaw,astheformswereonlysignedbyoneof
theparentsratherthanthemandatorytwo”.
The official position of the Ministry of Health mentioned
thefollowing23:
“According to the conclusions of the Central
Ethics Committee of MoH Ukraine dated
02.03.2011 (№ 5.12‐228/KE) and of the MoH
Ukraine State Expert Centre dated 09.03.2011
(№ 193/KD), post‐registration clinical trials of
the drug “Jintropin” were conducted in the
Department of Paediatric Endocrinology of the
InstituteofEndocrinologyandMetabolisminthe
period from 10.03.2011 to 10.03.2012, within 6
months, on 30 patients with growth hormone
deficiency. The drug has been registered in
Ukraine since 21.04.2009 (registration
certificate number 259). Since that time it has
beencentrallypurchasedbyMoHUkraineandis
usedonchildrenwithgrowthhormonedeficiency
inUkraine.
During treatment, no side effects or negative
consequences, or indeed deaths, were recorded.
Allchildrencompletedtreatmentwithapositive
clinical outcome (satisfactory gain in growth).
Regardingthepatients’informationalconsent:in
26casesitwassignedbybothparentsandbythe
patient,andin4casesitwassignedbyoneofthe
parents”.
©BerneDeclaration,September2013
10
The MoH statement raises several questionable points.
Firstly, after using the term “clinical trial” in the first
paragraph, it mentions only “treatment”. Clinical trials are
nolongermentioned.Secondly,thedeputiesmainlyclaimed
in their statement that there had been irregularities in the
informed consent procedure. The MoH noted, for its part,
that there had been no fatal cases. However there was no
mention of any child deaths by the deputies. Why did the
officialshavetojustifythemselves?
Ashasalreadybeenmentioned,aninformedconsentform
mustbesignedbybothparentswhenchildrentakepartin
clinical trials. If it is signed by only one parent when both
are alive, it is considered a violation of the law. And if it is
signed by a grandmother or aguardian, or adirector of an
orphanage,itprovesthatthechildisanorphan.Bylaw,the
participationoforphansinCTsispermittedonlyincasesin
whichadrugisvitaltosavethelifeofachild.
Finally,theMoHofficialsadmitthattheinformedconsent
procedure had breached the law in 4 cases (9 according to
thedeputies),asconsenthadbeengivenbyonlyoneofthe
parents. The law requires the signature of both parents,
even if they are divorced or separated. The MoH did not
explainwhythishadhappened.Theydidnotevenmention
thefactthatonehadbeensignedbyagrandmother,asthe
supervisor of this CT told a TV channel. This fact indicates
that the child lives without parents. No explanations were
given as to why an orphan child was included in the CT
group.
Neither was there any mention, in the MoH statement, of
thesupervisorsendingalettertotheOfficeoftheChildCare
Services regarding this trial. In contrast, the MoH did give
thisinformationforthebosentantrial.Why?
The answers to the above‐mentioned issues could not be
obtained from the Ministry of Health. Officials refer to the
fact that the position of the MoH is fully explained in their
pressrelease.
2.1.3. AnalysisoftheDoripenemtrial
TheallegedunethicaltrialsinPoltavaarethosethathave
thegreatestresonance.
Deputy Valery Golovko accused physicians from Poltava
Regional Hospital of, firstly, conducting “illegal trials of
dubious drugs on children”, and secondly, of enrolling
“orphansinclinicaltrials”.
Thedeputy’sstatementsays24:
“In Ukraine, clinical trials of drugs that have
been recently submitted for registration have
been conducted with numerous procedural
violations. A striking fact is that orphans are
involvedinthetrialsbeyondtheexpirationofthe
ClinicalTrialsinUkraine
insurancepolicyorwithoutthepermissionofone
oftheparentsand,evenworse,withviolationsof
the informed consent procedure for the child
patients. These elements are observed in many
health care institutions. There are cases of
clinicaltrialsinvolvingchildreninthePaediatric
Department of the Poltava Regional Children’s
Hospital, in particular the multicentre clinical
trial of the drug “doripenem”. It is known that
theaccreditationcertificateforthishospitalwas
missing for almost a year and a half (from
20.11.2010to17.02.2012)”.
The Ministry of Health has denied all the deputy’s
accusations through an official statement that says, in
referencetothisspecificcase25:
“Conductingclinicaltrialsisaprocedurecarried
outbynumerousmedicalandscientificresearch
institutions in Ukraine, under the control of the
MoHUkraineStateExpertCentre,toevaluatethe
efficacy of a drug. This medicinal product is
already registered, has passed extensive testing,
and is permitted to be used in Ukraine. This
procedure is governed by the current of MoH
Ukraineorder№690dated23.09.2009.
TheMinistryofHealthimmediatelyrespondedto
the published statement and requested that the
[…] Department of Health of the Poltava
Regional State Administration confirm or deny
theclaims.Thefollowingreplieswerereceived.
Poltava Regional Children’s Hospital is the
clinical base of the chair of the Department of
Paediatrics number 2 of the higher state
educational institution of Ukraine, “The
Ukrainian Medical Stomatologic Academy”. The
Academy,inturn,istheclinicalbaseoftheMoH
Ukraine State Pharmacological Centre and, asa
clinical centre, has all the permits to conduct
clinicaltrialsofdrugs.
In the period of June to September 2012, during
clinical trials of the drug “doripenem”, two
children were treated. This medicine is an
antibacterial agent and is used to treat urinary
tract infections. It is authorised for use in
Ukraine (registration certificate number
UA/9213/01/01, valid from 17.12.2008 to
17.12.2013).
In the patients’ medical records there is an
informed consent form signed by both parents,
whichisarequirementfortheinclusionofachild
in clinical research monitored by the Ethics
©BerneDeclaration,September2013
11
Committee of Poltava Regional Children’s
Hospital. Today these children are in sustained
remissionofthedisease”.
By law, participants have to be provided, by the CT
sponsors, with insurance that guarantees them
compensationintheeventthatthestudyharmstheirhealth
or is fatal. This is standard procedure for all participants,
including orphans. Previously, CT sponsors were able to
avoidhavingtoprovideCTparticipantswithinsurance,but
after the recent legislative changes it has now become
obligatory.TheMinistryofHealthhasstatedthatCTscannot
beginuntilallparticipantsareinsured.Thestatementofthe
deputies, however, suggests that insurance coverage was
notprovidedduringthewholedurationofthetrial,whichis
aviolationoftheexistinglaw.
The involvement of children in CTs falls under the
authority of Yuri Pavlenko, Presidential Commissioner for
Children’sAffairsinUkraine.Hepromisedtoinvestigatethe
situation and find out whether violations during CTs in
Poltava Regional Hospital had occurred or not. However,
according to informed sources, he visited the hospital in
Lubny – located halfway between Kiev and Poltava – and
hadatalktherewiththephysiciansduringhisfieldvisitin
March,butdidnotgotoPoltava.
Afterwards,hetoldjournalists:
“The Prosecutor’s Office, the Regional Health
Administration of Poltava Regional State
Administration and the Ministry of Health
carried out an investigation and concluded that
noclinicaltrialsortestingofanydrugorvaccine
inthePoltavaregion,orinthewholeofUkraine,
were performed. Firstly, it is forbidden by law.
Secondly,inthisperiod,whichwasmentionedin
the deputy’s statement, the vaccines in question
were not available in the region. In Poltava, the
medical records of all orphans and children
deprivedofparentalcare,whowereinhospitals
in the years 2011‐2012, were reviewed. As a
result,notraceorreferencethattrialsortesting
had occurred in the region of Poltava were
broughttolight”26.
Experts from patients’ organisations have stated that the
investigation of the Presidential Commissioner for
Children’s Affairs was that in appearance only. He did not
study the situation in the field and did not even go to the
Poltava Regional Hospital. There were no reports
confirming that he had met with the children and their
parentsmentionedinthedeputy’sstatement.Moreover,the
Commissioner got the type of product being tested mixed
ClinicalTrialsinUkraine
up: the CT was not conducted on a vaccine, but on an
antibiotic. His statement reveals his incompetence in this
area.
ThePresidentialCommissionerforChildren’sAffairsdoes
not know whether the law permits clinical trials involving
children to be conducted or not. The Ministry of Health
confirmsthattheCTshavebeencarriedoutandnamesthe
drug, but Yuri Pavlenko states that the CTs have neither
been conducted in the Poltava region, nor in Ukraine in
general.Howcanheidentifyviolations,ifhedoesnotknow
theregulations,CTstandards,etc.?
Alltheaboveconfirmsthatgovernmentofficialsavoidthe
topic,arenotinterestedinhowCTsarecarriedoutanddo
notknowtheregulations.
Furtherinvestigationrevealedsomeinterestingfacts.
The Poltava Hospital management states that “until
17.02.2012 the drug “Doribax” (“doripenem”) had not been
usedinthe Regional Children’s Hospital”,butitdoesspecify
whenitwasactuallyused.TheMinistryofHealthreported
that the CTs were conducted in the period from June to
September 2012. However, in early January 2012, the US
Agency for Food and Drug Administration (FDA) published
information on the early termination of a clinical trial of
Doribax (doripenem) due to safety concerns. The
manufacturersoftheantibioticdecidedtoexpanditsfieldof
application and organised CTs during which the efficacy of
thedruginthetreatmentofpatientswithvariousformsof
pneumonia was tested. However, the result was not as
expected. Patient clinical recovery numbers were too low
and the death rate in the group receiving doripenem was
higher than in the control group, in which a different drug
wasused.
“Itturnedoutthatthemortalityrateofpatients
is higher, and the clinical cure rate is too low,
compared with the group of patients receiving
imipenem‐cilastatin”27.
TheFDA,whoseverdictisbindingandmustberespected,
reminded the experts that in the USA “Doribax” is not
approvedforthetreatmentofanytypeofpneumoniaandis
contraindicatedinadosageover500mgevery8hours.
How, then, is this antibiotic recommended for use in
Ukraine? The product is registered in Ukraine and the
instructions contain all the necessary information. Firstly,
Doribax is recommended for the treatment of adults –
people over the age of 18. Secondly, the list of diseases
comprises pneumonia, intra‐abdominal infections,
complicatedurinarytractinfectionsandpyelonephritis.The
dosage is the same for all diseases: 500 mg every 8 hours,
thecourseoftreatmentfrom7to14days.
©BerneDeclaration,September2013
12
The prescribing information also states that “there is no
experienceofusingthisdrugforchildrenunder12yearsold”.
Whyisthisagementioned?Isthereanydataonuseofthe
drugforthe12to18agegroup?Thisisnotspecified.
Can this be considered a violation of the treatment
process? It should be considered that Doribax is not
recommended for patients under 18 years of age. It was
therefore clearly a CT and not treatment, according to
standards approved by the Ministry of Health. Taking into
account the information from the FDA, it can be concluded
thatthehealthofchildrenwasexposedtorisks.Butneither
thephysiciansnortheofficialsrecognisethis.
The prescribing information indicates that the drug can
cause side effects, and recommends consulting a doctor
immediately if the following occurs when taking Doribax:
severeallergic reaction,hives,difficultybreathing,swelling
of the mouth, tongue or face, chest pain, bloody stools,
fatigue,severe diarrhoea,severecramps,etc. Thedoseand
administration details include the threat of serious side
effects, including “lethal hypersensitivity reactions –
anaphylaxis”. It is not excluded that such kinds of
complications arose during the CTs of the drug in the
treatment of pneumonia, as a result of which the FDA
orderedtheirearlytermination.Thefactthatchildrenwere
treated in cases of urologic diseases, not in cases of
pneumonia,didnotmeanthattheywereprotectedfromthe
sideeffectsthatmighthaveoccurredatanytime.
Did the physicians know about this? They must have
known.Didtheparentsknow?Itisunknown.Mostprobably
they did not know what kind of drug their children were
injected with and they did not read the prescribing
information.
One of the reasons that could influence the decision of
parentstoinvolvetheirchildreninCTsisthepoorstateof
the health system and their low income. According to the
Constitution of Ukraine, medical assistance should be
publicly funded. However, patients have to buy everything
attheirownexpense,includingdrugs,syringesetc.Perhaps
thisiswhyalmost90%ofdrugsinUkrainearesoldfreelyin
pharmacies without any need for a prescription. This
includesantibiotics.
Thecostofapackof“doripenem”(10vials)ismorethan4
thousand hryvnia (about 450 euros). For a course of
treatment a minimum of three packs, as well as syringes,
droppers, etc., need to be bought. Taking into account the
lowwagesinUkraine,aswellasthelowlivingstandardsin
general,itisunderstandablethatsomeparentsacceptoffers
for their child to take part in clinical trials. The physicians
veryoftendonotevenpronouncethewords“clinicaltrial”.
ClinicalTrialsinUkraine
2.1.4. Conclusionsandunansweredquestions
The contradictions of the doripenem case reflect how
government officials, namely the MoH and the Presidential
Commissioner for Children’s Affairs, dealt with
communications. First they wrote on their official website
thattherehadbeennoclinicaltrialsinvolvingchildrenatall.
ThentheywrotethattherehadbeenCTswithchildrenbut
without violations. They even named hospitals which were
not mentioned in the deputy’s statement. The MoH stated
thatalltheCTshadtakenplacewithoutincurringviolations,
butitdidnotgrantpermissiontotalktothechildren,their
parentsorguardians.
Manyquestionsarethusleftunanswered.
For example, what was really done to the children in
Poltava Regional Children’s Hospital: were they treated
accordingtoatreatmentprotocolapprovedbytheMinistry
of Health or were they participants of a CT? The same
questionarisesfortheothercontroversialtrialsofbosentan
andJintropin.
PharmaceuticalcompaniesaffirmthatchildreninUkraine
arebeinggiventheopportunitytobetreatedwiththelatest
drugs. Experts from patients’ organisations believe that
adults are using children as a resource for carrying out
clinical trials. In so doing, they do not really care about
children’shealthandrights.
Hospital executives in Poltava state that no violations
occurred. They also say that there have been no CTs. This
was a treatment procedure in which two children were
injectedwithanantibioticprescribedforurologicdiseases.
Theconsentformtousethemedicationhadbeensignedby
both parents. However, the response of the Ministry of
Health clearly states that “during the clinical trials of the
“doripenem” drug two children were treated”. Who is lying
then:theheadphysiciansortheMinistryofHealth?
According to the law, there is no need for any signed
permission from the parents in the routine treatment of
children.Ifaninformedconsentformhasbeenregisteredby
the hospital, then it was a CT rather than standard
treatment. The hospital categorically refused to give any
information about the children, the contact details of their
parents or their general practitioner. As always, patient‐
doctor confidentiality and the Law on the Protection of
PersonalDatawerereferredto.
Researchers have informally reported28 that the above‐
mentionedclinics,whereCTswithchildrenwereconducted,
did not have accreditation at that time. This means that
violationsofthelawhaveoccurred.Thereasonissimple:at
thattimetheMinistryofHealthwasnotissuingtherelevant
documents. There was an ongoing management change in
theMinistryofHealth,manycommitteeswerenotworking.
Thatiswhyapplicationswerenotconsidered.
©BerneDeclaration,September2013
13
The scandal was eventually silenced. State officials
declaredthattherehadneverbeen,noraretherenow,any
problems with CTs involving children. All the deputies’
statementsweredeclaredtobepoliticalprovocationsfrom
theopposition29.
2.2.Theproblematicdoctor‐patientrelationship
Ukraine has a long‐established tradition according to
which a patient fully trusts his/her doctor and follows
his/herrecommendations.Typically,adoctor’sadvicedoes
notcauseconcerntothemajorityofpatients.
Doctorsfrequentlyabusethispositionofpowerovertheir
patients. According to testimonies of the relatives of those
who took part in CTs, physicians, in order to recruit
participantsfromtheirpoolofpatients,sometimestellthem
that new drugs have been received as humanitarian aid.
“They are very expensive, but we could make an exception
for you and you will get it for free. Please sign the form to
showthatyouagreetoreceivethem.Andthatyouwillnot
payforthem”,theysay.Peopleagreetothis.Parentsofchild
patientsalsosignallthedocuments,becausethetreatment
of chronic diseases is very expensive, they have no
insurance, their wages are low. In addition, patients and
theirfamiliesunderstandhowdependenttheyareontheir
doctor.InUkraine,giventheprevailingconditions,itisvery
difficult,ifnotimpossible,torefuseadoctorandtogoand
see another for treatment. This is pointed out by patients
themselves,byexpertsfromNGOsandbylawyers.
A dramatic recent example of patient abuse: the Kiev
PsychiatricHospital
The Kiev Psychiatric Hospital, named after Pavlov, is the
main medical institution in the mental health service
system. Our investigator has visited it several times,
includingwithaTVcrewreportingonthepreparationofthe
Ukrainian law on psychiatric care and patients’ rights as
well as with international organisations in 2011 and 2012.
Allthevisitorswereshockedbywhattheysawthere.
This hospital has special status and outsiders are not
allowed to visit it. Having a press card does not help gain
access. Medical buildings are locked, windows are barred,
and patients only go for a walk accompanied by nurses.
Communicatingwiththemisprohibited.
In March 2013, a TV programme that specialises in
investigative journalism conducted an experiment to
investigatethewaypatientsaretreatedthere.Ayoungman
asked one of the doctors at this institution to hospitalise a
middle‐aged woman. His version of events was that “the
woman is the mother of his wife, has a very difficult
character and disturbs the life of the young family”. The
request was to isolate the woman, to punish her for
ClinicalTrialsinUkraine
interfering in the family matters of her daughter, to scare
her,tomakeherquiet.Themediareportedthatthedoctor
agreed to hospitalise the healthy women for 1000 hryvnia
(approximately95euros).Thedoctorpromisedtomakeher
life hell. The conversation with the doctor was recorded
withahiddencamera30.
Thedoctorsaid:
“Shewillbetormented;thewomanpatientswill
beat her. Her head will be hit against a toilet
bowlinthebathroom.Adrunkennursewillbeat
her at night. This will be hell! I assure you that
there are people in the hospital under false
pretence and good money is paid for it! The
money is not spent in vain. The woman will not
receive any treatment there, no sedation,
nothing! She will suffer! You will pay every
month. And who knows how long your relative
will live. She could live for five years and she
couldliveforonlytwomonths”.
At first, the hospital refused to comment on the case in
question, then it was said that this case was slander. Later
on it was revealed that the doctor mentioned in this case
hadbeenfiredfromthepsychiatrichospital31.
InlateMarch,itwasreportedthatthepsychiatrichospital
had no money for medicine and food for the patients.
©BerneDeclaration,September2013
14
However, under the law, this should all be funded by the
StateandbythemunicipalityofKiev.
Theninformationcameoutrevealingthatsomepatientsin
the hospital do not receive food or even water. Some are
givenonlyporridge,breadandtea.Thereareroomstherein
which people live out their lives in terrible suffering.
AccordingtoinformationmadeavailableontheInternet,the
prosecutor’s office began an investigation into this
psychiatric hospital. The reason given for this was a
statement claiming that mentally sick people were being
forcedtosigndocumentsgivingawaytheirapartmentsand
otherpropertytotheirrelatives32.
The patients without relatives are also put at risk.
Inadequate treatment leads to rapid deterioration of their
health,sometimeseventolossoflife.Theirpropertyisalso
given away to others. The prosecutor’s office is still
investigating the issue. No additional information has
appearedbecauseofthesecrecyoftheinvestigation.
It is well known that psychiatric hospitals have special
status. In the Soviet era the psychiatric service was part of
the penal system: people who were against the state were
oftensentthere.Obviously,somefeaturesoftheoldsystem
stillcontinuetobeinforcetoday.
Theabove‐mentionedjournalisticinvestigationhasshown
that patients’ rights in the hospital are promised but not
observed.
ClinicalTrialsinUkraine
15
Mythnumber3:Clinicaltrialsitesmeetinternationalstandards.
What guides CT organisers in selecting clinical trial sites?
Officials claim that they are guided by legal requirements,
whichstrictlyregulatethisissue.Thegovernment,through
the Ministry of Health and the State Expert Centre (HEC),
considers all proposals, analyses the capabilities of each
hospitalorcentreand,onlyaftercarefulchecking,makesa
decision.TheCTsitesshouldtheoreticallybelocatedonlyin
higher‐levelhospitals,wheremedicalschoolsarebasedand
wherehealthcareisprovidednotonlybyregularphysicians
butalsobyuniversityprofessors.
Municipal (i.e. ordinary city) hospitals, which are not
teaching hospitals, cannot and should not be CT sites. The
main reasons for this are: poor resource infrastructure, a
lack of modern diagnostic and laboratory facilities, andthe
lower professional qualifications of the medical staff. Many
drug CTs involve critically ill patients, e.g. patients with a
myocardial infarction, stroke, lung diseases, cancer and
other complex diseases. In such cases, intensive care and
emergency units, modern equipment, tools and medicines
are needed, but are either not available at municipal
hospitals or are in poor condition. Physicians in such
hospitals do not have the appropriate qualifications or
experience of running a CT. All these factors can have a
significant impact on the progress and results of the CT.
Therefore, these municipal hospitals are not officially
includedinthelistofCTsites.
However, recently, CT participants have asserted that the
sites are only selected by CT sponsors, which are
pharmaceuticalcompanies.Iftheynameahospitalthatthey
arecomfortablewith,itisincludedinthelistofCTsites.The
lawalsoleavesroomforthesponsortoselecttheCTsite33.
The State Expert Centre states that the list is compiled in
compliance with all legal requirements governing CTs, but
that may be seriously questioned. Officials claim that all
hospitals in which CTs are held have advanced equipment,
diagnostic facilities, certified laboratories, and well‐trained
medical staff. These are the arguments used to attract
foreignpharmaceuticalcompaniesinterestedinconducting
CTsinUkraine.
However,itisevidentthathealthcareinUkraineislagging
behind world standards. The health system has been
gradually destroyed by years of underfunding, corruption
andtheincompetenceofitsmanagers.AccordingtoArticle
49 of the Constitution of Ukraine, medical care is free of
charge for citizens. This means that it should be funded
through the State budget. As there is no social security
(insurance) system, the State budget is the only source of
financingforthecountry’shealthsystem.
These facts are known by the managers of multinational
pharmaceuticalcompaniesthatareplanningtoconductCTs
©BerneDeclaration,September2013
in Ukraine. Companies from many different countries have
representative offices in Ukraine; they have been doing
business here for a long time, monitoring changes in
legislation,analysingmediareports,etc.
Those that work in the field of medicine know very well
that, since the Declaration of Independence of Ukraine in
1991, the Ministry of Health has replaced 16 or 17 of its
ministers. Some of them held the post for only 4 to 8
months.Naturally,thishashadahugeimpactonthehealth
careindustry,leadingtoitsdeterioration,povertyandlack
ofqualifiedhumanresources.Forthelastthreeyears,allthe
attention of the MoH has been devoted to putting out
tenderstodeterminewhichcompanieswillsupplymedical
equipment, medicines, vaccines, medical materials, etc., all
fundedbytheState.Onaverage,overthelastfewyears,the
Ministry of Health has had an annual budget of about 7
billion hryvnia (roughly 650 million euros), spent on
medicalstaffsalaries,paymentoftherunningcostsofhealth
facilities, as well as on the implementation of government
public health programmes such as tuberculosis control,
HIV/ AIDS, immunisation of children, etc. According to the
MinistryofHealth,in2013,theMinistryreceivedonly19%
ofthefundingneededfromthecentralgovernment.
Officials do not like to recall these data. They are taken
from official sources, in particular, from the Supreme
Council’sHealthCommittee,articlesoftheLawapplyingto
the 2013 State Budget, and from the 5th report of the
Government of Ukraine on the implementation of the
EuropeanSocialCharterfortheperiodfrom1January2008
to31December201134.
InKiev,numerousCTsareconstantlybeingcarriedout.Do
Kievhospitals matchinternationalstandards?Accordingto
theKievStatisticsOffice,thedebtofKievhospitalsreached
170millionhryvniainthefirst4monthsof2013(about16
millioneuros).Medicalinstitutionsdonotreceivefinancing
for development, for new equipment, tools, repair works
and so on. More than 50% of the X‐ray equipment was
purchased over 15 years ago. Ultrasound equipment,
electrocardiographs and other diagnostic equipment are in
an equally poor state. Equipment often breaks down and
thereisnomoneyforrepairs,henceitisdifficulttodothe
necessary tests on schedule, essential during both regular
treatmentofpatientsandinCTs.
The above‐mentioned facts lead us to conclude that
hospitalsequippedwithoutdatedequipmentaswellaspoor
laboratory and diagnostic departments can barely serve as
appropriate sites for clinical trials of new drugs. It often
occurs that patients need to go through additional
diagnosticsandtestswhilelookingfortreatment,notinthe
state and municipal hospitals’ laboratories but in private
ClinicalTrialsinUkraine
ones, to verify the accuracy of a diagnosis. They do this
becauseofalackoftrust:theydoubtthattheequipmenthas
been correctly monitored and configured, and they do not
believe that the reagents in public laboratories are of good
quality.ThosewhoparticipateinCTsdonothaveachoice;
theyhavetoundergoalltheexaminationsatthehospitalin
which the CT is being conducted. Do they obtain accurate
results? Is it possible to trust 100% the reports of
physicianswhoconductclinicaltrials?
Journalists, together with patients’ organisations,
conductedanexperiment:adilutedsolutionofteawassent
tolaboratoriesinKievandKharkov.Intheiranalyses,only
one (!) of the 6 laboratories identified the solution as tea
andnotedthisinitsrecord.Theother5laboratoriesstated
in their records that it was urine, and even indicated a
proteinlevelandthepresenceofglucoseandminerals.
In2010‐2012ourinvestigatoralsoparticipatedinanother
experimenttogetherwiththepatients’organisation“Health
of the Nation”. Volunteers sent blood samples to several
laboratories (observing all necessary requirements) for
blood glucose testing. The results were catastrophic. The
laboratoriescamebackwithalevelofglucoseforthesame
personthatvariedbetween4and20units.
These results were shown to experts from the State
PharmacologicalCentreandtheywereaskedforcomments.
They replied that it was not an experiment, but a
provocation.
A conversation with V. Chumak (former director of the
MoH State Pharmacological Centre) turned out to be very
interesting. He is considered a highly competent person in
the pharmaceutical industry, an experienced manager. The
initialquestionsthatwereputtohimwere:isitpossible,in
such conditions, to trust the quality of the CT? And how is it
possibletoidentifytheeffectsandside‐effectsofadrugonthe
body of a CT participant if the majority of laboratories in
Ukrainedonotguaranteethequalityoftheirresearch?
InterviewwithViktorChumak,formerDirectorofthe
StatePharmacologicalCentreMoH
V.Chumak:Whyisitnotpossibletotrust?Anexperienced
physician determines, without laboratory tests, whether a
medicinehelpsapatientornot.
Journalist:However,aphysician‐researchermustkeep
arecordofalltheresultsofatrialandarecordofthe
laboratory diagnostics of a CT patient‐participant.
Whatdoesherecord?
V.C.:Herecordsthedatagivenbythelaboratory.Thereis
noreasonnottotrustitsresultsifthelaboratoryiscertified
andhasaworkpermit.
©BerneDeclaration,September2013
16
J: A base/site in a poor state and problems with
laboratory services may lead to results of CTs in
Ukraine differing from those obtained in other
Europeancountries.Dothesponsoringcompaniespay
attentiontothisfact?
V.C.:Whyshouldtheydiffer?Infact,allCTsareconducted
accordingtothesamerules.Andifasponsoringcompanyis
alerted to something, a physician who conducts a CT can
always be asked to check everything again. Usually, the
results of CTs conducted in Ukraine are beyond doubt, the
indicatorsarethesameasinothercountries.
Discussions were also held with the pharmaceutical
experts from the Ministry of Health, who said almost the
samething.
The previously mentioned scandal at the Kiev Psychiatric
Hospital (see 2.2) is also very worrying as this institution
alsoconductsclinicaltrials,includingSwissones35.
The Ukrainian Psychiatric Association has confirmed that
clinical trials of mental health drugs are carried out in this
hospital. How are the CTs conducted there? The hospital
authorities state that everything is done according to the
law. Informed consent forms are signed by the patients
themselvesorbytheirrelativesortrustees.
Butdoesahospitalofthiskindmeettherequirementsof
thehealthcareinstitutionsinwhichCTsareconducted?Can
the informed consent forms of CT participants be trusted?
Have they been signed according to all the rules? Do
patientsunderstandwhattheyaresigning?Iftheinformed
consent form is signed by relatives, are they really
interested in a positive outcome from the patient’s
treatment or are they just interested in receiving the
patient’shouseorotherproperty?
As she was looking for information about CTs in the
hospital in question, our investigator contacted the
associations of psychiatrists (there are several of them in
Ukraine).Noneofthephysiciansagreedusinghis/hername.
Eventhosewhoareconsideredtobeleadingexpertsasked
not to broach the subject of CTs in psychiatric hospitals,
claiming that – since there is no money for the necessary
medicine – CTs provide free treatment and a chance for
thesepatients,ifnottobesaved,thenatleasttohavetheir
sufferingeased.
To the question “Do the patients receive medicine or
placebos?”ourinvestigatorwasassuredthattheyaregiven
medicine and that no one is left without help. None of the
physiciansshowedaninformationalconsentform.
ClinicalTrialsinUkraine
17
Mythnumber4:CTsinUkraineareunbiased
Independent observers and experts are increasingly
talkingaboutthefactthatdrugcompaniesarefindingways
to “programme” the results they need. Members of the CT
subcommittee of the European Business Association
(EBA)36, which includes local representatives of the
multinationalsPfizerandRoche,wereaskedtocommenton
thisissue.
Allofthemstatedthatpharmaceuticalcompaniesconduct
CTs exclusively to obtain objective information in order to
determine the effect of a drug on the human body. The
pharmaceuticalindustryspendsalotoftimeandmillionsof
dollarsproducingasafeandeffectivedrug.
Independent experts consider that, for the sake of profit,
pharmaceutical companies are seeking ways to reduce the
cost of the CT process. This is why they choose developing
andemergingcountries,includingthepost‐Sovietcountries,
with low salaries and very low insurance costs for CT
participants compared with Western countries. They are
alsointerestedinreducingthetimeofCTs,inparticularthe
periodofrecruitmentofCTparticipants.Thismayevenlead
toasituationinwhichphysiciansrecruitmoreparticipants
thannecessaryforaCT.Alltheseviolationsarecausedbya
desire to beat the competitors and bring a drug to the
marketasquicklyaspossible.
An “industry bias” in CT results was confirmed by
researchers from Toronto and Harvard Universities in
©BerneDeclaration,September2013
201037. They studied CT results in relation to funding
sources for five groups of drugs, including antidepressants
andoncologydrugs.Datafrom500CTsshowedthat85%of
the industry‐sponsored trials gave positive results. The
other government‐funded trials showed more modest
results – only 50% of the products received a positive
evaluation. In a similar 2007 study of statins (cholesterol
treatment)38, researchers concluded that trials funded by
the pharmaceutical industry were 20 times more likely to
giveresultsfavouringthetesteddrug.
In Ukraine it is alleged that pharmaceutical companies
suggest to physicians and researchers what indicators
shouldbeusedforasuccessfulCT.Inthiscase,theyreferto
the fact that CTs have already been completed in some
countries and obtained positive results. Hence the same
results should come from Ukraine. Such advice is
“considered” by physicians and influences their work. The
reason is simple: the salary of a doctor is very low, on
average 2‐3 thousand hryvnia (200 to 300 euros). It is
legallypermittedtoearnmoremoneythroughCTs,totake
part in scientific conferences abroad, etc. Working in
conditions such as those that prevail in Ukraine, it is very
difficultforadoctortobeindependentandtokeephis/her
own point of view. For this reason they mostly follow the
“advice”ofthesponsors.
ClinicalTrialsinUkraine
18
Mythnumber5:SponsoringcompaniesareintotalcontrolofCTs
Following the CT controversies involving children, the
European Business Association (EBA) sent out a press
release on 18 March entitled “Safety of clinical trials in
Ukraine”thatbasicallysaidthefollowing:
“Members of the European Business Association,
represented by leading international companies
and conducting clinical trials in Ukraine, are
extremely concerned about theinterpretationof
clinical trials as a result of the statement of the
groupofdeputiesdated11March2013.
We consider that the information given in the
statement and presented as “fact” should be
carefully checked to avoid possible unfounded
accusations, which can affect the reputation of
medicalinstitutionsandtheirstaff.Therefore,in
our view, Ukrainian society is not well enough
informedaboutclinicalresearchandthebenefits
itundoubtedlybringstothecountry.CTsprovide
severely ill people with free‐of‐charge, high‐
quality treatment using modern highly
innovativedrugs.Takingintoaccountthecritical
situation of the health care system and the low
income of the majority of Ukrainians, they are
extremelyimportant”.39
The CT system is organised in such a way that
pharmaceuticalmanufacturersoftenhavenodirectrelation
totheCTprocess.TheresponsibilityofcarryingouttheCT
usuallyfallstoanintermediary,acompanywhichorganises
clinicaltrialscalledaContractResearchOrganisation(CRO).
Everything ends up in the hands of physician‐researchers.
How CTs are conducted depends a great deal on their
professional and ethical skills. Surely there are physicians
who do their best to meet all the requirements of the law.
However,thereareotherswhopermitviolationsanddonot
see it as a problem. For example, when our investigator
travelledtoLviv,KharkivandPoltava,sheoftenheardthatit
isnotthatimportantifaninformedconsentformcannotbe
signedbyapatient;afamilymembercandoit.Ifapatientis
not capable ofdeciding by himself/ herself, the rules allow
that an “outsider” – a so‐called “witness” – sign the form
instead of the patient. Experts believe that this is a direct
wayforviolationstooccur.Ahospitalemployeecanbecome
an“outsider”,andthepatient’srelativeswillnotevenknow
thathe/sheisinvolvedinaCT.
In Kharkov, some students and teachers told our
investigator off the record that students participate in CTs.
This fact was also mentioned during a congress on CTs in
Kiev. There are many higher educational institutions in
©BerneDeclaration,September2013
Kharkov,amongthemtheNationalUniversityofPharmacy,
whereCTsareconducted.Surely,itismuchfastertorecruit
a group of volunteers if they are students, who are highly
dependent on their teachers and the dean to succeed.
Documentaryevidencecouldnotbeobtainedtobackupthe
claims. Students claimed that they were asked to take part
inclinicaltrials,andthatiftheyrefusedtheycouldbegiven
lowscoresintheirexams.Theycouldnottellmorebecause
theywereafraidofbeingexpelledfromtheuniversity.This
issueshouldbeinvestigatedfurther.
Human rights workers claim that a great number of
violations occur during the CT participant recruitment
process. This is the opinion of the paediatrician N.
Kolomiets, a representative of the NGO “League for the
ProtectionofCivilRights”.
“It is hard to quickly bring together a group of
volunteerstoparticipateinaCT.Notallparents
give their consent to involving their children in
experiments.Thatiswhytheylookfor boarding
schools, orphanages and orphans living with
guardians. Including these children in CTs is
simple: managers of orphanages and boarding
schoolssigninformationalconsentformswithout
askingquestions.
Mentally ill people, single old men, vulnerable
people, who are not protected by anyone, are
involvedinCTs.Iknowofsuchcases”.
Organisers of CTs and physician‐researchers deny these
facts.Theyconsiderthewordsofthehumanrightsworker
tobeslander.
All physicians who conduct CTs state that they adhere
strictlytotherequirementsofthelaw.
Yaroslav Shparik, PhD, an oncologist at Lviv National
MedicalUniversity40,gavethefollowinganswers:
InterviewwithYaroslavShparik,oncologist,Lviv
NationalMedicalUniversity
Journalist:Howdoyouformagroup(howlongdoesit
take,whatarethecriteria,etc.)?
Y.Shparik:Agroupofpatientsisformedaccordingtothe
typeofdisease.EachCThas30to50criteriathatneedto
be analysed. The duration depends on the kind of group
thatisformed.Ifforexample,weneedpatientswithbreast
cancer that require postoperative chemotherapy, then ten
patientscanparticipateeverymonth.IftheCTisrelatedto
a rare type of tumour, with rare characteristics (e.g.
ClinicalTrialsinUkraine
mutation), it may take many years, with potentially no
resultsattheend.
J:Towhatshouldpatientspayattentionwhensigning
aninformationalconsentform?
Y.S.:Theyshouldreaditcarefully,consultthosewhomthey
trust and ask the physician all the necessary questions.
Issues related to the safety of the treatment, and to
patients’rightsandduties,areespeciallyimportant.
J: Have you experienced cases, in your practice, in
which people have refused to continue their
participationinaCT?
Y.S.: Refusals once treatment has begun happen rarely. A
patientquicklybecomesconvincedthathe/sheisreceiving
high‐quality (often the best possible) treatment. Very
careful (more accurate than in routine practice)
observation of a patient is carried out. Tests are often
conducted in leading laboratories in Europe and the U.S.,
additionalmonitoringmethodsareused,etc.
Sometimeseventhetransportcostsarecoveredbysponsor
companies(inarecentstudyourpatients,togetherwitha
guide, were brought by train to Kiev, travelling business
class, and from the railway station to the clinical trial by
taxi). A lot of patients quickly learn the value of the
therapy,thecostofwhichmaybehundredsofthousandsof
hryvnia,andwhichtheyreceivefreeofcharge.Isitlogical
torefuseit?
SometimesthepatientisnotallowedtoparticipateinaCT
bythephysicians,whoconsiderthathe/shewillnotfollow
protocol. We have to work with unpunctual, “forgetful”,
irresponsiblepeople.DuringaCT,thesecharacteristicsmay
createadditionalrisksforthepatients.
J: The Chairman of the National Commission on
Bioethics criticised our CT system for its insurance
scheme, which is very different from its European
equivalent.Insurancepayoutsaremiserablecompared
toothercountries.Whatisyouropinionaboutthis?
Y.S.:Unfortunately,researchersdonothaveaninfluenceon
the policy of insurance companies. At the end of the day,
this isanissuethat concerns not only CTs, but alsohealth
©BerneDeclaration,September2013
19
insurance (particularly for travel abroad), car insurance,
etc.Afterall,theseinsurancepaymentshaveacorrelation
with the income of our citizens. Can we have an influence
onthis?Itisnotthefaultofthesponsors,butmoreofthe
insurancecompanies.
J:WhatisthemostdifficultaspectofworkingwithCT
participants?
Y.S.:Themostdifficultaspectisdispellingmythscreatedby
the media, like “Ukraine is a testing ground for foreign
pharmaceutical companies” or “patients are experimental
guineapigs”,etc.
ClinicalTrialsinUkraine
20
Mythnumber6:IndependentethicalcontrolofCTsisguaranteed
It is essential that all participants are protected during a
CT.In2012,theMinistryofHealthintroducedfundamental
changestotheset‐upoftheEthicsCommittee.AnOrderwas
issued (11.04.2012 № 255)41 abolishing the Central Ethics
Committee, which had operated under the Ministry of
Health.Sincethen,inhospitalswhereCTsareconducted,a
localethicscommittee(LEC)hashadtobecreated.Thisisa
long and complex process. For Ukraine it is a new
experience; there is no clear information on how to do it.
Therearemanyorganisationalissuesrelatingtowherethe
LECmembershavetoworkandstoredocuments.
Whereas CTs continued to be conducted at all sites, local
ethics committees were not in place and the central
committeewasnotoperationalanymore.Moreover,changes
were introduced in the summer of 2012, when many
researchersanddirectorsofclinicswereonholiday.
Our investigator managed to talk with several LEC
representatives from clinics in Kiev. Not officially, but on
conditionofanonymity.Evenbytheendof2012,LECshad
notyetbeensetuporbecomefullyfunctionaleverywhere.
OneofthereasonsisthatLECmembersarevolunteers,i.e.
they have to work in their free time and are not
remunerated. The average salary of a doctor, equivalent to
250‐500euros,ismuchlowerthanintheindustrialsector.
Healthprofessionalsareinterestedinearningextramoney.
Nobodywantstospendtimeonthoseactivitiesthatdonot
generatefinancialincome.Hence,LECsarenotreallyactive.
Inofficialinterviews,doctorsandlawyerssaythereareno
problems,andLECmeetingsareheldonschedule.Asthere
aremanydocumentstoreviewandapprovewithin7days,
LECsshouldmeetatleastfourtimesamonth.ButmanyLEC
memberssaytheymeetonlyonceamonth.
Maryana Kotsyba‐Suvalo, Lviv Regional Hospital lawyer
andLECSecretary,gavethefollowinganswers42:
InterviewwithMarinaKotsyba‐Suvalo,lawyer,Lviv
RegionalHospitalandsecretaryoftheLocalEthics
Committee(LEC)
Journalist:WhatdoestheLECdo?
M. Kotsyba‐Suvalo: The LEC evaluates the ethical and
legal aspects of each CT, including the patient enrolment
procedure. Its conclusions can be positive or negative.
Particular attention is given to those patients who are
incapableofdiscernmentandtominors.
J:WhoarethemembersoftheLEC?
M.K.: Ithas 5 members: the head of the LEC is thedeputy
©BerneDeclaration,September2013
chiefphysicianoftheregionalhospital.Thedeputyheadis
a Professor of Neurology from the Medical University. The
LEC also comprises the head of the obstetric division and
the deputy chief surgeon. The secretary of the LEC is a
lawyer‐consultant,namelyme.
J:HowfrequentlydoestheLECmeet?
M.K.: The law (MoH Order) already exists, but the
implementationprocedure,withpreciseinstructions,isnot
yet in place. So the LEC meets according to the needs as
therearemanydocumentstoreview.
J:HowmanyCTsareheldinyourhospital?
M.K.: It is a big clinical trial site, many CTs are held here.
Sometimesthereare40ofthemorevenmore.
J: Which pharmaceutical companies from what
countriesapplyforaCT?Whatdrugsarebeingtested
here:cardiology,cancerorsomeothers?
M.K.: Different manufacturers choose our hospital, from
many countries within and outside Europe. But I cannot
give you more information, as it is a commercial
confidentialityissue.
J:HastheLECreceivedanycomplaintsfrompatientsor
fromtheirrelativeswhenproblemshavearisenduring
aCT?
M.K.:Asalawyer,Ihaveadutytoprotecttherightsofour
patients.AndIdo.SincetheestablishmentoftheLECthere
haveneverbeenanysuchcomplaints.
J: What kind of complaints might patients have while
participating in a CT? What problems might arise
duringtheCT,inyouropinion?
M.K.:Therehavebeennocomplaintsandnoproblems.We
are working to explain everything about CTs to our
patients.Doctorsuseaterminologythatisdifficultforthe
patient to understand, the language in the informed
consentformsistoocomplicated;itiseasierforalawyerto
explain everything to the patient in a way that is easy to
understand.
J:Whodraftstheinformedconsentforms?Canyougive
us an example of how you explain the difficult terms
andconditionsofCTstothepatients?
ClinicalTrialsinUkraine
M.K.: We use the forms we are provided with. They are
prepared by the pharmaceutical companies and are
validated by the central authorities. But showing them to
peoplewhoarenotpartoftheCTisstrictlyprohibited.This
is confidential information, and the sponsor companies
categorically prohibit it. I can only say that everything is
presented in such a way that the interests of the patients
anddoctorsinvolvedinaCTaretakenintoconsideration.
J: As a lawyer, you probably know what financial
compensationisforeseenin casesinwhichtheCThas
causedthehealthofyourpatienttodeteriorate?
M.K.: This is confidential information as well. Nobody has
therighttodiscloseit,onlythesponsorcompanies.
J:Thelawforeseesthatthepaymentshouldnotbeless
than a certain limit. Recently amendments were
introduced to the legislation: what is the minimum
amount now? Do you have to say this to patients who
participateinaCT?
M.K.: Why are you always interested in confidential
information? All those of us who are connected with CTs
sign a confidentiality form and we are not allowed to
discloseinformation.SoIcannotsay.
J: What do you have to do when a medicine provokes
sideeffects?Towhomdoyoureport?
M.K.:Researchersreporttotheethicscommitteeandtothe
sponsorcompanies.
J:Doesitoftenhappen?
M.K.: Sometimes it happens, but not often. The ethics
committeeconsidersthecaseanddecideswhattodonext.
Traditionally, many clinical trials are held in
Dnepropetrovsk, where the population is more than 1
million inhabitants. Here, future doctors are trained at
Dnepropetrovsk Medical Academy, in the Medical Institute
ofPostgraduateStudiesandtheInstitutesandClinicsofthe
Academy of Medical Sciences. All this is taken into
considerationbysponsoringfirmsandtheyorganiseclinical
trials here. One of the largest clinical trial sites is the
DnipropetrovskCityHospital.HeretheLECwascreatedand
is headed by Nikolaï Shinkarenko, whom was also
interviewed43.
©BerneDeclaration,September2013
21
InterviewwithNikolaïShinkarenko,headoftheLEC,
DnepropetrovskCityHospital
Journalist: For how long have CTs been held in your
hospital?
N. Shinkarenko: The hospital has participated in clinical
trials since 1991. Since that time, we have signed 156
contractsforclinicaltrials.
Itisamunicipalinstitutionwith800hospitalbeds;wealso
haveaclinical‐diagnosticdepartment.Thereareatotalof
17divisions,ofwhich7aretherapeuticand10surgical,as
well as many laboratory facilities. Every year we treat
24000patientsandperform8000surgicaloperations.The
main division is oncology, where about 3500 patients are
being treated. Therefore, one of the areas of clinical trials
hereisoncology.
We also have medical school departments: oncology,
nuclear medicine, internal medicine, cardiology, and
pathology.AllexceptthelastonedoCTs.Forclinicaltrials
the fact that the clinic has a Department of Pathological
Anatomy, employing high‐class specialists, is of great
importance.
Upto10%ofourpatientsparticipateinCTs.Thenumberof
cancer patients is more than 350 ‐ 400 a year, which is a
lot.
J:HowdoestheLECworkinyourhospital?
N.S.:TheLEChasalotofworkandgreatauthority.Bylaw
itisimpossibletoconductclinicaltrialsinaclinicwhereno
LEChasbeenestablished.CTsarenotheldinthosecasesin
whichtheLECdoesnotagree.Asponsormaythenapplyto
another medical institution, where there is an LEC, and
workthere.
J:WhoarethemembersoftheLEC?
N.S.: At present our LEC consists of 8 people: five doctors
from various specialties, a priest, a lawyer and one
engineer. All candidatures were approved by the hospital
administration.
Members of ethics committees cannot know everything
about the drugs that are tested. The LEC has the right to
turn to experts for advice to help to evaluate all the
informationaboutthedruganditscharacteristics.
J:WhendoestheLECmeet?
N.S.: The LEC must meet after business hours. It’s hard.
There are no stipulations in the Ministry of Health Order
concerninghowoftenweshouldgather.Itisrecommended
that we meet no less than once a month. How to do this?
ClinicalTrialsinUkraine
22
Themeetingsarelong;weneedtostudyallthedocuments,
understand everything. We cannot rely on doctors for
explanationsastheyareondutyandbusywithpatients.
We are a public organisation, and we have a serious
responsibility.Itwasmucheasiertoworkwhentherewasa
CentralEthicsCommitteeattheMinistryofHealth.
We need facilities for the LEC meetings, for meetings with
researchersandparticipants of CTs, as well as for storage
of numerous documents. The clinic cannot provideenough
freespace.Thisisabigproblem.
J:WhoapprovesthemembersoftheLEC?
N.S: The members are approved by the head physician of
thehospital.
We study the history of the disease, talk to patients and
theirrelativesandconsidertheiropinion.Welearnhowthe
informedconsentformwassigned.Wealwaysremindthem
©BerneDeclaration,September2013
that we have a “Data Protection Act” and a “Law on the
ProtectionofPersonalData”.EverythingconcerningtheCT
is confidential, it is not for outsiders. All the issues are
discussedonlywiththeparticipantsoftheCT.
For the different reasons mentioned above, it can be said
that the ethical supervision/control of CTs – although
stipulatedandregulatedbylaw–isnotguaranteedand/or
is influenced by conflicts of interests on the part of
doctors/researchersorhospitalmanagers.
ClinicalTrialsinUkraine
23
Conclusion
TheissueofCTsiscomplexandsecretive:onlyverylittle
information can be obtained from public sources. If a
journalisttriestoinvestigatetheissuesofCTs,he/shefaces
many hindrances and difficulties in the search for
information. This is why journalists rarely write about this
topic.
The scandal which broke because of deputy Golovko’s
statementmadethetopicofCTsatopnewsitem.However,
only the statement of the deputy and the answers of the
Ministry of Health were reported. No journalistic
investigation or analytical articles followed. The reason for
this is obvious: it is almost impossible to get any
information.
Consequently, some people became aware that the CT
systemisnotascorrectandaccurateasitisclaimedtobeby
those who finance and conduct clinical trials. Some people
startedtofindoutwhatmythsprevailintheCTsystemand
what the realities and facts are. The main conclusion to be
drawn is that not only patients, but also pharmaceutical
manufacturers, should thoroughly analyse whether or not
the legislative regulations are being properly met. From a
corporate behaviour perspective, carrying out studies on
one or more children, including orphans – who need even
more protection as vulnerable subjects – in a context of
weak ethical supervision and regulatory mechanisms, is
irresponsible.
It is difficult to judge clinical trials conducted in Ukraine.
ThenumberofCTsincreaseseveryyear,butthereisalack
ofinformationaboutthem.SinceUkrainehasahighlevelof
corruption–andmedicineisnoexception–publictrustin
officialsandthehealthsystemislow;itisverydoubtfulthat
clinical trials are conducted in strict compliance with the
law.
The legal framework in Ukraine meets international
standards; the rules of CTs are equivalent to thosein West
Europeancountries.However,therearemanywaystoincur
violationsintheimplementationoftherulesgoverningCTs,
especially as clinical trials are turned into an exercise of
financial gain for some of those involved. International
organisations like the World Health Organisation and the
Parliamentary Assembly of the Council of Europe have
repeatedly pointed out that the health care system in
Ukraine is insufficiently financed. There is still no social
security (insurance) for medicine in Ukraine. The
infrastructure of hospitals and laboratories is lagging
behind modern requirements. The outdated equipment
©BerneDeclaration,September2013
affects the accuracy of diagnosis and the suitability of the
prescribed treatment. Under these conditions, it is very
difficult to conduct clinical trials according to all the rules
andtoachieveaccurateresults.
Every year, more and more European pharmaceutical
companiesapplytoconductclinicaltrialsinUkraine.Swiss
companieshavebeencarryingoutCTsinUkraineforyears.
Duringtheinvestigationourinvestigatormanagedtotalkto
representatives of Roche Ukraine. She was not able to visit
theclinicalsite:theinterviewstookplacein theoffice.She
was not allowed to meet the patients who took part in the
clinicaltrials.AtNovartis,ameetingdidnottakeplaceatall:
several arrangements were made over the phone for a
meeting, but it was repeatedly postponed and never took
place.
The recent CT controversies have drawn public attention
tothosehospitalswhereCTsareconducted,includingthose
where Swiss companies operate. Another scandal is linked
to the Kiev Psychiatric Hospital, where CTs have been
conducted for many years. The list of clinical trials
sponsoredbySwisscompaniesincludesthetestingofdrugs
on schizophrenic patients. Pharmaceutical manufacturers
have refused to answer where (site) these are taking place
andwhichdrugsarebeingtested.However,inKievthereis
onlyoneclinicalsitewheresuchtrialsareconducted.Thisis
thehospitalwhereTVjournalistsfilmedthestoryaboutthe
mishandling of patients by doctors. How can the CT be
carriedoutinsuchconditionsandwithsuchspecialists?Are
theresultsoftheseclinicaltrialsreallyreliable?
Experts from patients’ organisations claim the sponsor
companies have a special interest in conducting clinical
trials in Ukraine as it is much cheaper than in other
European countries. For example, the maximum insurance
payouttoaCTparticipantwas,foralongtime,betweenone
andtwothousanddollars.Afterthe2012amendmenttothe
legislation, the minimum payment should not be less than
10thousanddollars.
CTs should not be an issue only for business, medical,
patients’rightsandethicsspecialists.CTsconcerneveryone.
Afterall,whenbuyingamedicine,eachofusbelievesthatit
will have the positive effect described in the leaflet.
Therefore,weshouldallbeconcernedthatclinicaltrialsare
being conducted in accordance with legal regulations and
ethical requirements, and that they are not biased so as to
favouranexaggeratedpositiveresult.
ClinicalTrialsinUkraine
24
Annex:listofinterviews
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
M.Sereda,medicaldirectorofRocheUkraine
S.Mikhailov,headoftheClinicalTrialsSubcommitteeoftheEuropeanBusinessAssociation
V.Chumak,formerdirectoroftheStatePharmacologicalCenteroftheMinistryofHealth
V.Serdyuk,presidentoftheAll‐UkrainianCouncilofpatients’rights
O.Skorina,headofthelegalserviceoftheAll‐UkrainianCouncilofpatients'rights
N.Kolomiets,leaderofthepublicorganization"Leagueoftheprotectionofcivilrights”
Y.Shparik,oncologist,LvivNationalMedicalUniversity(recommendedbyRocheUkraine)
A.Morozov,vicedirectoratStateExpertCenteroftheministryofHealthofUkraine,professor
A.Bazilevich,professoratLvivNationalMedicalUniversityafterD.Galitsky
M.Gzhegotsky,deputyofthegeneraldoctoratLvivRegionalHospital
I.Zakalyuzhniy,lawyeratLvivRegionalHospital,memberofthelocalethicalcommittee
M.Kotsyba‐Suvalo,lawyerattheLvivRegionalHospital,secretaryofthelocalethicscommittee
S.Rasputnyak,DeputyDirectoroftheDepartmentofPre‐ClinicalandClinicalStudies,TheStateExpertCenterofthe
MinistryofHealthofUkraine
N.Shinkarenko,headofthelocalethiccommissioninDnipropetrovskStateHospital
G.Legeza,representativeoftheNGOprotectingpatients(Dnipropetrovsk)
V.Kornatsky,formerdirectoroftheCentralEthicsCommitteeoftheMinistryofHealth
V.Ocheretenko,DirectoroftheNGO"HealthoftheNation"
N.Polischuk,ex‐MinisterofHealth
14.
15.
16.
17.
18.
Interviews(withoutrecorder)werealsomadewithstaffmembersoftheKharkivNationalPharmaceuticalUniversity,ofthe
DnepropetrovskMedicalAcademy,andoftheNationalMedicalUniversityBogomolets.
©BerneDeclaration,September2013
ClinicalTrialsinUkraine
25
24
PreviouslycalledStatePharmacologicalCenter(SPC),
http://pharma‐center.kiev.ua
2Allthefigurescitedinthisintroductionaretakenfrom:Clinical
TrialsMarketinUkraine(Part2),JournalofClinicalStudies,Vol3
Issue6,December2011(http://jforcs.com/jcs/downloads/clinical‐
trials‐market‐in‐ukraine‐part‐2/)
3OCTQuarterlyNewsletterIssue2(www.oct‐clinicaltrials.com)
4
http://marketing.scripintelligence.com/files/2013/01/UkraineProf
ileSampleNov2012.pdf
5TheJournalofClinicalStudies,ibid.
6AlllegislativetextsinUkrainiancanbefoundat
http://zakon.rada.gov.ua
7SeeIntroduction,http://zakon.rada.gov.uaand
http://arzinger.ua/en/press/publications/42613/
8http://glavnoe.ua/news/n135826:“Ukraineintermsofpress
freedomfor2012dividedthe131‐134thplacewithZambiaand
SouthSudanamong197surveyedcountriesandterritoriesand
barelyrestrainedinthecategoryof"partlyfree,"saidthehuman
rightsorganizationFreedomHousefromtheU.S.tothereport
releasedtoday.Thesethreestatesarethelatestinthiscategory
witharatingof60points,thenextcategorybeing"notfree"
countries."(unofficialtranslation)
9Seeannex1foracompletelistofinterviewees
10EuropeanBusinessAssociation.EBAisanon‐profitorganization,
whichunitesover950foreignanddomesticcompaniesoperatingin
Ukraine.AtpresentEBAisaleadingorganizationofforeign
businessinUkraine(http://www.eba.com.ua/)
11Accordingtoourinvestigations,bothRocheandNovartisareor
wererecentlyconductingPhaseIIandPhaseIIItrialson
schizophreniadrugsinthishospital.
12Seeamongothers(inUkrainianandRussian):
http://www.pravda.com.ua/news/2013/03/11/6985223/,
http://www.unian.net/news/558321‐oppozitsiya‐trebuet‐
rassledovat‐ispyitanie‐lekarstv‐na‐detyah.html,
texty.org.ua/pg/news/movchun/read/44127/Opozycija_zvynuvac
huje_vladu_v_doslidah_nad_ditmysyrotamy,http://magnolia‐
tv.com/text‐news/2013‐03‐12/22169‐m‐l‐ts‐ya‐poltavshchini‐
perev‐rit‐nformats‐yu‐shchodo‐viprobuvannya‐vakts,
http://www.poltava.pl.ua/news/21015/,
http://ukranews.com/ru/news/ukraine/2013/03/11/91717),
http://www.privivok.net.ua/smf/index.php?topic=1235.0;wap2,
13ibid
14FortheoriginalMOHpressstatementinUkrainian,see
http://www.moz.gov.ua/ua/portal/pre_20130312_a.html(last
accessedon18/07/2013)
15Ibid
16Seemediareportsfn10
17TheChildCareServicesaretheState’ssocialservicesfororphans
andsemi‐orphansinUkraine.Alsocalledguardianshipservices,
thesedonotonlydealwithchildrenwhohavelosttheirparents.If
theparentsleadanantisociallifestyle–e.g.alcoholordrugabuse,
neglectofchildren–theycouldbedeprivedoftheirparentalrights.
InUkraine,childrenwhoseparentshavebeendeprivedofthese
rightsarealsocalledorphansorsocialorphans.Eithertheir
relativeslookafterthemandbecometheirguardians,orthesocial
servicesforchildrenandchildren’sorphanagestakecareofthem.
18http://www.privivok.net.ua/smf/index.php?topic=1235.0;wap2
19InUkraine,accordingtothelaw,citizensbelow18yearsofage
areconsideredminors
20www.clinicaltrials.gov(lastaccessedon18/07/2013)
21
http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089801.pd
f
22Seemediareportsfn10
23SeeofficialMOHpressstatementfn12
1
©BerneDeclaration,September2013
seemediareportsfn10
seeofficialMoHpressstatementfn12
26Seehttp://np.pl.ua/2013/03/yurij‐pavlenko‐zhodnyh‐
vyprobuvan‐vaktsyn‐na‐dityah‐syrotah‐na‐poltavschyni‐ne‐
provodyly/
27http://www.rusmed.info/cont/osobennosti_glaukomy.html
28Ontheconditionofanonymity
29InUkraine,aftertheparliamentaryelectionsinOctober2012,the
confrontationbetweenthegovernmentandtheopposition
escalateddramatically
30http://news.liga.net/news/capital/845861‐
skandal_v_psikhlechebnitse_kieva_prodazhnyy_vrach_otstranen_ot_
raboty.htm#,http://ru.sn.ua/ukrayina/v‐kievskoy‐durdome‐
vrachi‐ustroili‐konclager‐kormyat‐tolko‐kashey‐i‐sozdali‐palaty‐
smertnikov‐301430.html,http://glavnoe.ua/news/n134607
31http://www.aif.ua/society/news/57819
32Ibid
33Seeart3.4oftheMOHOrder№690of23.09.2009:“Theselection
ofresearchersandhealthcarefacilities(healthcareinstitutions‐
hospitals)reliesonthesponsor.Requirementsforresearchersand
healthcarefacilitiesarelistedinSectionVofthisOrder.Sponsors
maydelegateanyorallofitsfunctionstoacontractresearch
organization(…)”.(http://zakon.rada.gov.ua,unofficialtranslation)
34
http://www.coe.int/t/dghl/monitoring/socialcharter/Reporting/St
ateReports/CommentsAllUkrainianCouncil2013_en.pdf
http://www.coe.int/t/dghl/monitoring/socialcharter/Conclusions
/State/Ukraine2009_en.pdf
http://www.coe.int/t/dghl/monitoring/socialcharter/Reporting/St
ateReports/Ukraine1_en.pdf
35Seefn10
36http://www.eba.com.ua/
37
http://www.stcharlesresearch.org/images/RepDrugTrialOutcomes
%20AnnIntMed%208‐3‐10.pdf
38
http://www.plosmedicine.org/article/fetchObject.action?uri=info
%3Adoi%2F10.1371%2Fjournal.pmed.0040184&representation=P
DF
39http://www.eba.com.ua/static/press‐
releases/PR_HCC_18_03_2013_ukr.doc(OriginaltextinUkrainian,
lastaccessedon18/07/2013)
40HewasrecommendedtoourinvestigatorbyRocheUkraine
41AlllegislativetextsinUkrainiancanbefoundat
http://zakon.rada.gov.ua
42Theinterviewtookplaceattheendof2012
43Theinterviewtookplaceattheendof2012
25

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