Embed Size (px)
Citation preview
1
Systematic Review on clinical trial participants: Indian perspective
M. Sc. Thesis Report (2008-2010)
Submitted to
Institute of Clinical Research, India (ICRI)
&
Cranfield University, UK
Submitted by:
Machut Zimik
D-1017
2
DECLARATION
I hereby declare that the thesis work entitled “Systematic Review on Clinical Trial Participants:
An Indian Perspective” submitted to the “Cranfield University” and “Institute of Clinical
Research India” is a record of an original work done by me under the guidance of Professor Phil
Warner (Cranfield University) and Dr. Amit Kumar Verma (Institute of Clinical Research India).
3
ACKNOWLEDGEMENT
Firstly, I must thank my mentor Dr. Amit Kumar Verma for his continuous support and guidance
throughout my academic programs. Without his constant support and inputs I could not have
finished this thesis.
I would also like to thank Professor Phil Warner for his valuable expertise and pointers which
helped me immensely to frame my thesis work appropriately.
Last but not least a special thanks to all my friends and family for their support and prayer which
enables me to complete my thesis effectively and on time.
4
ABSTRACT
The globalization of clinical trial has substantially increased the participation of India thereby
becoming one of the hotspot destinations for conducting global clinical trial sites. At present,
India being one of the fastest in patient enrollment rate , certain ethical concerns has been raised
fearing that the cultural and socio-economic background are exploited to enhance the research
programs. There is clearly a large knowledge gap between the researchers and the potential yet
vulnerable participants. With a large number of people now participating in a clinical trial, it is
important to determine their willingness to participate in a clinical trial.
The reviewer conducted a systematic review of all studies that emphasize on the contributing
factors and barriers on trial participants within the Indian populations. An online database was
searched both International as well as Indian journals. The study included in the final analysis
dealt exclusively with only Indian population participating in a clinical trial. Data extraction and
validation was conducted by the reviewer alone.
The final evaluation comprises of five qualitative studies and two surveys. The themes included
in the participants favoring factors include personal benefits, social benefits; generate extra
income, knowledge associated with the trial, motivating methods for participation and physicians
while themes acting as barriers for participation include logistical problem and misconception,
concern about the treatment, fear, confidentiality issues, psychosocial factors and mistrust
towards sponsors.
Factors that facilitate participation and factors that act as barriers among Indian subjects were
identified by the reviewer. Before initiating a clinical trial it is important to consider patient’s
perspective on participation and accordingly plan for any future implementation.
5
CONTENTS
Declaration ……………………………………………………………………… 2
Acknowledgement ……………………………………………………………… 3
Abstract …………………………………………………………………………. 4
1. Introduction...………………………………………………………………...7-8
2. Literature Review
2.1. Systematic Review……………………………………………………...9
2.1.1. Importance of Systematic Review………………………………..9-10
2.1.2. Appraisal of Systematic Review………………………………….10-13
2.2. Patient recruitment……………………………………………………….13-14
2.2.1. Difficulties faced in recruitment process…………………………14
2.2.2. Reasons of patient participation in clinical trial…………………..14
2.2.3. Roadblocks to patient participation in clinical trial……………….15
2.2.4. Background on clinical trial participants………………………….15-16
2.2.4.1. Indian scenario………………………………………………..16-17
2.2.4.1.1. Advantages of conducting clinical trial in India……….17
2.2.4.1.2. Factors affecting patient recruitment in India…….........18-20
2.2.4.1.3. Rationality of the study ………………………………..20-21
3. Aims……………………………………………………………………………22
4. Objectives………………………………………………………………………22
5. Research Methodology…………………………………………………………23
5.1. Defining Research Question……………………………………………….23
5.2. Ethical Approval……………………………………………………………23
6
5.3.Selection of Studies………………………………………………………..23
5.4.Following keywords were used as a search strategy………………………24
5.5.Inclusion/Exclusion Criteria……………………………………………….24-26
5.6.Study Characteristics………………………………………………………26
5.7. Interpretation……………………………………………………………...26
6. Results …………………………………………………………………………27-29
6.1. Contributing factors that favor subject participation in a clinical trial……..30
6.1.1. Personal benefits……………………………………………………31-32
6.1.2. Social benefits………………………………………………………32
6.1.3. Generate extra income………………………………………………32-33
6.1.4. Knowledge associated with the trial………………………………...33
6.1.5. Motivating methods for participation ………………………………233
6.1.6. Physicians …………………………………………………………..34
6.2.Barriers to participate in clinical trial……………………………………….34-35
6.2.1. Logistical problem and misconception……………………………...35
6.2.2. Concern about the treatment………………………………………....35-36
6.2.3. Fear…………………………………………………………………..36
6.2.4. Confidentiality issue…………………………………………………36
6.2.5. Psychosocial factors………………………………………………….37
6.2.6. Mistrust towards trial sponsor………………………………………..37
7. Discussion………………………………………………………………………...38-47
8. Conclusion………………………………………………………………………..48-49
References ………………………………………………………………………………..50-53
7
1. INTRODUCTION
It is estimated that an average of 6% of the entire clinical trial budgets are being spend on subject
recruitment strategy (advertising and marketing) by global pharmaceutical companies and
biotech sponsors (1). Notwithstanding the amount of this investment by pharmaceutical
companies about 86% of the clinical trial surprisingly does not meet recruitment expectation (1).
More than 80% of clinical trial fails to enroll subjects on time globally, which can amount to loss
of 85%-95% of days in a clinical trial (2). This has made subject recruitment one of the most
challenging aspects to the sponsors. India offers a numerous advantages to the sponsors because
it provides a large patient pool to facilitate faster recruitment rate, cost effective clinical trial,
world class hospitals and clinical research facilities besides availability of a highly qualified
professionals.
It is apparent that global clinical research is exploring in India in an exponential manner. The age
old technique of medical research begin long time ago in India since the two ancient scripts
Charaka Samhita (a textbook of medicine) and Sushruta Samhita (a textbook of surgery) written
as early as 200 B.C and 200 A.D. However, the current scenario in clinical research is
spearheaded by USA, UK and Japan after they jointly proposed the ICH (International
Conference of Harmonization) guidelines. After recognizing the potential to outsource clinical
trials in India because of certain advantages the growth of clinical research industry in India has
been expanding rapidly.
Since mid 1990 India started conducting International Clinical trial though it was until 2005 that
the regulation on clinical trials began to change rapidly. A report from a conference at the
Institute of Clinical research (India), Mumbai Oct. 2008 by DCGI stated that 582 registered
8
clinical trials are being conducted in India (3). With more than 150 CRO’s and a number of
pharmaceutical companies now operating in India the rate of conducting clinical trials are very
much on the rise. It is apparent that India being a favored destination for conducting global
clinical trial the number of NDA is increasing in a large scale. This had eventually led to the
increase in recruitment of study subjects. Patient recruitment itself is a big challenge as it is with
Research and development. Pharmaceutical companies and CRO’s are now professionalizing in
recruitment activities to overcome the hurdles of missed deadlines, more cost and delay in
approval. The increased in the participation of multi-site studies has raised certain ethical
concern particularly on the study subjects fearing that their local customs, cultures and habits are
not respected by exploiting their economic status and leaving them no choice rather than forcing
them to participate in a study.
Unfortunately, the absence of affordable health care and poverty in India can be easily exploited
by CRO’s and pharmaceutical companies to enhance their research overlooking the integrity of
patients. It is estimated that approximately 5,300 subjects are required per NDA (4) and India
being 10 times faster in the rate of patient recruitment in contrast with US it is important to
identify the factors that led to patient participation in India. Conducting a systematic review on
the contributing factor of patient recruitment in India would serve as an ideal way of assessing
this attributes.
9
2. LITERATURE REVIEW
2.1. Systematic Reviews
A systematic review is a scientific tool that can be used to appraise, summarize, and
communicate the results and implications of otherwise unmanageable quantities of research.
Systematic Review utilizes the availability of evidence and evaluates the number of studies
conducted separately to synthesize the result. Depending on the similarity of the studies
systematic review may or may not utilize meta-analysis (5). Meta-analysis is considered optional
components of systematic review.
Meta-analysis is however a part of systematic reviews and involves statistical technique for
generating combining data to bring about a summary result. For the purpose of this thesis
systematic review will be use for the process of finding, selecting, apprising, synthesizing, meta-
analysis and interpretation of results.
2.1.1 Importance of Systematic Review:
Systematic Review
Meta-analysis
10
Helps decision makers and healthcare providers summarize large amount of research-
based data/information
Helps overcome bias among clinical trials and other research-based studies
Helps resolve conflicts in results of several studies
Helps to evaluate generalizability of conclusion
Helps to overcome inadequate size of individual studies
Conclusions can be drawn by considering all the available evidence
2.1.2 Appraisal of systematic reviews:
During systematic reviews, a conventional and rigorous methodology is developed to reduce
bias. Implementation of appropriate methodology for conducting systematic reviews and
minimizing bias during reviews can help enhance the appraisal of published articles.
Steps in developing systematic reviews:
I) Defining a research question:
This includes a thorough research on the related topics of interest and frame the
importance of answering a certain question that needs attention. The reviewer should
clearly state the question that needs to be addressed.
II) Selection Criteria:
Selection Criteria are considered depending on the clear question of the systematic
review such as population, intervention, age, ethnicity, outcome, etc. This will help as
a source of generating a set of inclusion and exclusion criteria of the study review.
Further it will determine if the searched literature can be assessed against the
11
selection criteria of the study to be reviewed. The selection criteria must also reflect
on the objectives of the systematic reviews.
III) Searching the literature:
Searching a literature both from published and unpublished articles can be an
immense work and therefore should be carefully plan so that only the appropriate and
relevant studies could be searched. For instance, in systematic reviews of prevention
and treatment intervention, comparative randomized trials are most commonly used
to reduce bias. Depending on the interest of systematic review both electronic
databases as well as non-English sources can be searched.
IV) Assessment of included studies:
Assessing the selected studies is important in determining the validity of the searched
articles that needs to be included in the systematic review. Validity assessment should
be presented clearly.
V) Combining the results:
All the individual studies included in the review are aggregated to summarize the
overall effect of each study. In this step meta-analysis are utilized to analyze the
overall result of the included studies.
Meta-analysis is done in a two-stage process:
Data extraction
Calculation of result
VI) Interpretation:
The findings from meta-analysis are interpreted depending on the results of met-
analysis and further address the accountability of the findings.
12
Defining a Research Question
Selection Criteria
Searching the Literature
Assessment of included studies
Combining the results
Interpretation
Figure 1 Overview of systematic reviews
Systematic reviews provide the best possible estimate among all other studies of any true effect.
A relevant clinical or any research question can be answered appropriately only if the systematic
13
review are conducted with high quality and properly implemented. Gaining access to relevant
and reliable evidence could hugely favor on the outcome of systematic review. On the contrary, a
well conducted systematic review will immensely help the researchers, decision makers,
investigators, clinicians and practitioners.
2.2. Patient Recruitment
A successful completion of a clinical trial depends on the timely enrollment of patient
participants. A new molecules is expected to take 10-15 years to reach a market of which
30 percent of it are spend on recruitment of patients (6). Patient recruitment is therefore
considered as the “key bottle-neck” of clinical trial because it can either accelerate or
undermine the success of a clinical trial. The USFDA requires a minimum of 4,000
patients per drug to be tested so as to obtain for approval and marketing authorization.
Yet less than 5% of US populations are willing to participate in a clinical trial. This could
prove costly for the pharmaceutical companies since nearly 1 million dollars a day are
lost as revenue due to delay in gaining access to the market. A study by Rabo India
Finance ascertained that the cost of conducting phase I clinical trial in India is less than
half of the cost conducted in US while that of phase II cost almost 60% less.
Looking at the perspective of the companies cost effectiveness remains their prime
objectives and is looking towards countries like India and China where vast patient pools
are available. This has intensified competition within the pharmaceutical companies and
CRO’s which has made patient recruitment even more difficult. Currently pharmaceutical
companies are considering a major focus on patient recruitment strategy such as
identifying the demographics of the target population and other elements. As India is
14
attracting more and more clinical trials it might face the same problem of patient
recruitment like in western countries such as US and Europe. The availability of a
suitable subject will reflect on the timely implementation of the study and further add as
incentives to the funding and designing of the study (7).
2.2.1 Difficulties faced in Recruitment Process
Rare consideration of recruitment strategy during the protocol design
Narrowly defined inclusion/exclusion criteria
Inadequate budget allocations on recruitment process
Lack of basic knowledge by Investigator on patient recruitment
Negative publicity by the media
2.2.2 Reasons of patient participation in clinical trial
Willingness to help advance knowledge
Looking for a cure
Lack of available therapy
Better treatment
Higher quality care
Lack of health insurance
Advice by personal or family physician
Economic reason
Received money for participation
15
2.2.3 Roadblocks to patient participation in clinical trial
Risk of side effects
Language barrier
Not eligible
Psychological reason
Inconvenient hours and trial center
Trial burden
Concern about getting placebo
Fear of loss in confidentiality
Mistrust of trial sponsor
2.2.4 Background on clinical trial participant
Currently there is a mixed opinion on why some study subject participates while others
choose not to participate. A survey from Harris Interactive Poll on cancer clinical trial
showed that, 83% of adults encourage the concept of clinical trials and considered
essential, however only 3% of US oncology patients participate in clinical trial (8). In
another study of Harris Interactive Survey a staggering 71% of eligible subjects choose
not to participate in a clinical trial (9).
In a randomized clinical trial recruiting a patient has become one of the most major
barriers that may decide the fate of a new molecules or generic drugs. Various studies
identified some of the main barriers of patient recruitment such as race, personal reasons,
language problem, patient preferences, education, age, eligibility criteria and other factors
(11-27). Similarly numerous studies also suggested adequate measures that need to be
16
considered during patient recruitment process (28-34). Several organizations often face
financial problems and limited resources while addressing measures to overcome
recruitment barriers. The comprehensive list of recruitment barriers also makes it
impossible to generalize the individual differences such as lifestyle divergence, cultural
and religious differences, social and economic conditions. In a global clinical trial it is
important to consider the differences in social and cultural issues, as it is important to
focus on specific effective measures to minimize those barriers wherever the patients are
available.
2.2.4.1 Indian scenario
It was until recently that clinical research is evolving dramatically in India with the
constant increase in outsourcing by foreign pharmaceutical companies. However the
awareness of clinical trial among Indian people is very low as compared to European
countries and US. Prior to participating in a clinical trial 56% of Indian population are not
aware of clinical research and an overwhelming 97% of patients first came to know about
clinical trial through physician as compared to 23% in the US. The understanding of the
study in a clinical trial among Indian people is another major concern, since only 8% of
patients were able to make their decision to participate in a clinical trial as compared to
38% in the US.
In spite of all the issues of awareness among the Indian population clinical trials are
being conducted at a fast rate. The reason could be due to the amendment of Schedule Y
of the Drugs and Cosmetics Act of India which are upgraded as equivalent to the section
of USFDA to harmonize with the ICH standard. Since the regulatory barriers are being
17
removed to perform clinical trials and identifying the potential to enroll patient at much
faster rate, more pharmaceutical companies and CRO’s have now identified India as a
global hub for clinical research industry.
2.2.4.1.1 Advantages of conducting clinical trials in India
Today India possesses several unique criteria for becoming a preferred destination of
global clinical trials.
Figure 2: Advantages of conducting clinical trials in India
India advantage
western disease distribution
availability of high patient pool
treatment naive patient
low cost
highly qualified proffessionalsworld class hospitals
and CR facilities
no language barriers
high patient:doctor ratio
diverse cultural and socio-economic
background
18
2.2.4.1.2 Factors affecting patient recruitment in India
A written informed consent is usually given prior to participation in a clinical trial to
respect the integrity of the subject. In a country such as India illiteracy could lead patient
to participate in a clinical trial by applying pressure by the sponsors to enhance their
research without considering the ethical criteria. Factors such as geographical region,
culture, socio-economic background and other market related environment offer India the
potential to recruit large number of subjects even without advertisement or enrollment
campaign. Majority of the population in India are not supported by healthcare system
besides the private medicine support is very costly which is beyond the financial reach to
majority of the Indian population. As a result many people still rely on government run
health care support. It is through this hospitals and other health care support that refer
patients to enter clinical trial in major cities and towns. Some of the popular hospitals
with subsidized nature in India like AIIMS (All India Institute of Medical Science,
Delhi), CMC (Christian Medical College, Vellore) and TATA (Tata Memorial Hospitals,
Mumbai) attract a lot of patient from different parts of the country because of the
infrastructure, facilities and presence of ethics committee. These hospitals have a large
number of patient database of varying patient profile and has become the referral center
for enrolling patient in a clinical trial. At present more than 80 private and government
hospitals in India are engaged in international clinical trials. India now has conducted
more than 100 clinical trials involving around 15,000 patients.
It is imminent that the socio-economic factors have contributed in recruiting patient in
India due to poverty, illiteracy and other social ills. It is acknowledgeable that in India the
potential participants maybe either poor or illiterate and might not be able to decide on
19
their own to participate. The complicated nature of the clinical trial such statistical design
and procedure further adds up to their inability to understand the nature of the trial. Such
factors may contribute them to participate through socioeconomic compulsion regardless
of the risk and danger they may encounter. Moreover, in a country such as India where
huge numbers of population are illiterate the study subject could be easily coerced by the
researchers compromising the guideline adherence. Another compelling factor of patient
participation in clinical trial could be impoverishment. Almost all impoverish person in
India rely on government institution for their health. These people main factors for
participating in a trial could be to reduce their economic burden and gaining access to
free medication and treatment along with getting incentives and other benefits.
With the exclusion of few states in South India, majority of the people in India speaks
Hindi, while English has become as a common language for all official purpose.
However the fact is most of the people in India are illiterate and majority of them are
confine with their own local knowledge. This could be one of the major barriers for the
sponsor in patient recruitment. In an Indian context the most important element to enroll
patient could be overcome by giving a proper counseling and guidance by the
investigators. The sponsors in return are quick to response to this issue and are allowing
investigators to recruit patient for them by providing them with incentives and extra
benefits. Another cultural barrier in India is the family barrier where for instance if a
female is to participate in a trial she enters the trial only after consultation with either
husband or parents or other family members. Other factors such as feeling offended while
undergoing the procedure of the protocol (example getting pregnancy test, HIV test etc)
could play a significant role in their participation. Regardless of all those barriers one of
20
the main factors for participation could be due to deep respect towards physician. In other
way this cultural value of respect for physician in India has contributed to fast
recruitment rate. The cultural factors however have also imparted responsibilities towards
the physician to safeguard patient more carefully and appropriately.
2.2.4.1.3 Rationality of the study
In contrast with the western countries, most of the patient participants are treatment naïve
indicating the socio-economic factors and quality of life of those patients that may
possibly contribute them to enter a clinical trial. A study conducted by CRO Excel Life
Science showed that an overwhelming 97% of patients in India enter clinical trial because
of the advice or referral by their primary care physician (10). It is apparent that the
patients are either influence by their doctor’s advice or unwilling to deviate from the
doctor’s judgment. This may bring about conflict of interest particularly when the doctors
are paid for recruitment fees to recruit patients in the trials. Several studies have shown
that very few patients participate in a trial to receive money who might possibly have
overlooked the risk involve in participation.
ICMR guidelines clearly state that, payments to participant should not be so large or the
medical services provided to the study subject should not be so extensive so that the most
important factor a patient should enter a trial is through his/her willingness to participate
with a proper knowledge on all aspects of the trial.
In a culturally diverse country such as India it becomes a problematic since it is at the
epicenter of a global clinical trial. The growing R & D capabilities, enormous
professionals, improve infrastructure and large patient pool made India global site for
21
health research. One of the major reason India has become a suitable location for global
clinical trial is due to its enormous potential to enroll patients in a short time (35, 36) with
as much as ten times faster in enrolment rates than US (37, 38). Other factors like
heterogeneous population and variety of disease with incidence rates almost equivalent to
other developed and developing countries have also contributed to the advantage of India
as a global site for conducting clinical trial (39). However, more often the ethical criteria
are being overlooked as being shown in the enormous enrolment rate and other studies.
The economic status, illiteracy and cultural barriers make those populations vulnerable
not entirely knowing the outcome of the research.
At present only a limited number of studies have been conducted regarding the specific
contributing factors on patient recruitment in India. It would therefore be unreliable and
inconclusive to include those studies in the decision making process by the
pharmaceutical companies, CRO’s and other decision makers. This study will focus on
addressing the main contributing factors and roadblocks of patient enrollment within the
Indian population by designing a meta-analysis to determine the key issues. Highlighting
those factors will enable researchers to refocus and rethink their strategies with precision.
22
3. AIMS
To evaluate the factors affecting participation of Indian subjects in clinical trial
4. OBJECTIVES:
1. To identify factors that favours patient participation in clinical trial in India.
2. To identify barriers of patient participation in clinical trial in India.
3. To key out strategies for improving patient participation in clinical trial in India.
23
5. RESEARCH METHODOLOGY
5.1.Defining a Research Question:
The main objective for conducting this study is to identify the contributing factors of
patient participation in clinical trial within the Indian population. This study will evaluate
both the contributing factors and barriers of patient recruitment by utilizing meta-
analysis. Various experimental and qualitative studies relating to clinical trial conducted
from 1986-2008 will be included for the purpose of this study.
5.2.Ethical Approval:
Since the study will evaluate only published literature, ethical approval was not applied.
5.3.Selection of studies:
A comprehensive and systematic search for literature was performed from the following
online database.
Pubmed
PLOS Hub
Opengate
Cochrane
Medind
BMJ
Medknow
Springer
The Indian Journal of Medical Research
Indian Journal of Medical Science
The searched literature from these online databases was from 1900-2008.
24
5.4 Following keywords were used as a search strategy
Patient participation in clinical trial in India
Patient participation
Survey on subject participant
Patient enrolment strategy
Barriers in patient enrolment
Factors affecting patient enrolment in India
Subject participation in HIV clinical trial
Subject participation in cancer clinical trial
For a more comprehensive search the references from the retrieved articles were also read
for relevant articles.
5.5. Inclusion/Exclusion Criteria
The reviewer independently evaluated all the retrieved articles for inclusion and
exclusion criteria based on the objectives of the study that will answer the research
question.
Inclusion Criteria Exclusion Criteria
Studies or surveys confined to Indian Studies or surveys that include non-
Indians
Full text articles Articles that are not published
Experimental or Qualitative studies on
clinical trial
Studies that are not related to clinical
trial
Studies that include the factors affecting
patient participation in India
25
A total of 323 studies were identified for the purpose of this study. While going
through the abstracts 213 articles were excluded due to the following reasons:
No Indian population
Undesired outcomes
Studies not related to clinical trial
A further 103 were excluded due to the following reasons:
No Indian population
Non-availability of full text articles
Non research articles such as editorial, reports, news, opinions, and reviews
In the end, 7 articles were eligible as per the inclusion criteria and were involved in
the final analysis. The reviewer made one exception to the inclusion criteria by
including one study which was not published but the study survey data was presented
in one of the conferences and since the data was authentic it was justified to be
included in the final analysis.
26
Figure 3: QUOROM statement flow diagram:
5.6. Study Characteristics:
Descriptive data was collected from each study to be included in the meta-analysis. The
characteristic included in the study are demographic details of the study participants like
ethnicity, age, study outcome and country where the study was conducted.
5.7. Interpretation
The included study will be analysed by utilizing met-analysis. Two tables - 1.factors
favouring participation and 2.barriers to participation will be interpreted. The two tables contain
six themes each where a percentage will be calculated to determine which specific factors require
more attention.
Relevant articles identified on the basis of the title (n=323)
Total abstracts excluded (n=213)
No Indian population, undesired outcome, study not related to clinical trial.
After screening the abstracts (n=110)
Excluded articles after further screening (n=103)
No full text, no Indian population, not a research articles, undesired outcome.
Articles included for final analysis (n=7)
27
6. RESULT
All the data’s included in the meta-analysis were entirely reported from the Indian
population. Nevertheless two of the studies included were conducted in US and European
countries where Indian populations have participated while the remaining five studies
were conducted in India itself. Altogether seven studies were included in the final
analysis after considering all the inclusion and exclusion criteria. The studies taken from
the US and European countries had a mixed ethnic population. Out of the seven studies,
three were focused on participation in HIV vaccine trial while the remaining four were
study subjects that are already participating in clinical trials. Two studies had the same
author and respondent’s demography but the title and methodology were different; one
study was solely focus on structured questionnaire while the other study was about focus
group discussion. The minimum age participated among the seven studies was 15 years
of age. However, three studies did not mention the age group of the participants. Overall
numbers of Indian participants out of the seven studies are 1398. The intervention used
among the seven studies includes survey with structured and semi-structured
questionnaire, focus group discussion and online interview. All the data’s from the seven
studies are presented in the form of percentage which are shown in table 2 and 3
respectively. Apart from the tables, the reviewer also analyses the result by using quotes
from the respondents for better interpretation. After thoroughly reviewing all the data’s
from the included studies twelve specific themes were shortlisted for the final analysis.
Table2 represents the factors that favor patient participation while table3 represents the
barriers of patient participation in a clinical trial.
The overview of characteristics of the study is shown in table1:
28
Table1. Characteristic of the study:
Title of the study Study population
Age group
Location of the study
Purpose of the study
A pilot study on willingness to participate in future preventive HIV vaccine trials
112 (all Indians) -67 (male) -45 (female)
Above 15 India 1. Willingness to participate in a future HIV vaccine trial
2. Factors that enhance or deter these individuals from participating in a future HIV vaccine trial
3. Potential impact of HIV vaccine trial participation on risky drug and sexual behavior among these persons.
Correlates of HIV vaccine trial participation: an Indian perspective
349 (all Indians) -205 (male) -144 (female)
Not mentioned
India 1. To explore the level of concerns and preparedness for HIV vaccine trials among the persons with low and high risk for HIV infection
Involving South Asian patients in clinical trials
100 (20 Indians)
18 years and above
UK (Leeds and Bradford area)
1. Identify how South East Asian conceptualize and understand the notion of clinical trial
2. Identify the key process which impact on decision-making to participate in a clinical trial.
Participation in Clinical Trials Lower in Europe and India than in the United States
2935 (128 Indians)
18 years and above
US 1. Opportunities and
participation in clinical trials
2. Reasons for participation and likelihood of future participation
3. Factors Very Likely to Influence Participation
4. Risks and Benefits of Participating in Clinical
29
Trials Perceptions of a Community Sample about Participation in Future HIV Vaccine Trials in South India
112 (all Indians) -67 (male) -45 (female)
Above 15 India 1. Willingness to participate in a future HIV vaccine trial
2. Factors that enhance or deter these individuals from participating in a future HIV vaccine trial
3. Potential impact of HIV vaccine trial participation on risky drug and sexual behavior among these persons.
Recruitment of subjects for clinical trials after informed consent: does gender and educational status make a difference?
152 (all Indians)
Not mentioned
India 1. To find out whether patients are willing to participate in a clinical trial after receiving either partial or complete information regarding a trial
2. To test the depth of understanding patient who has consented to participate after full disclosure.
A survey on patient participation in clinical trial
525 (all Indians)
Not mentioned
India 1. To find out the patient recruitment procedure and inform consent quality.
30
6.1. Contributing factors that favor subject participation in a
clinical trial:
Table2. Factors favoring participation in clinical trial
Personal Benefits Social Benefits Generate extra income
Knowledge associated with the trial
Motivating methods for participation
Physicians
Less chance of getting infected with HIV
There will be an affective HIV vaccine in a few years
Money If they knew the risk associated with treatment
Internet (32)
Learn about clinical research study from regular physician
Protection from HIV
Vaccines will reduce the threat of HIV infection
Insurance If they knew the drug could cure them
Email notification (37)
Trust in government doctors for safety
Importance of HIV vaccine for self
HIV will become preventable like polio
Earn extra money
Understand the HIV/AIDS vaccine trial concepts
Physicians (97)
Doctors only do good
Better treatment Willingness is important for the common good of India
Receive money for participation
Belief in success of AIDS vaccine
The government agencies or the government television news channel
Out of obligation to doctor
Looking for cure Help researchers prevent HIV/AIDS
Harris interactive
Better treatment Even if the vaccine does not work, help researchers find an effective vaccine
Awareness of the HIV Vaccine campaign in India
Looking for observed benefit
Altruism Traditional media (eg. Newspaper
31
s, magazines, TV, radio)
Higher quality care
Advanced medicine and science
Free medication and medical care
Help others with the condition
Relief of pain Help advance scientific knowledge
If related to own health
Help medical community
To help the society To increase
scientific knowledge
37% 57% 30% 54% 32% 47%
6.1.1. Personal Benefits 37%
The number of studies contributing to this theme included all the seven studies.
Respondents tend to be more willing to participate if they are convinced that the trial
would personally benefit them associated with the condition (43). People think that if the
treatment are free and provide better treatment or may cure the terminal disease, they
would most likely choose to participate in the trial with the hope of improving the disease
or to cure them (43). Respondents felt that they would benefit from powerful vaccine by
involving in a trial and would completely protect them from HIV infection after the
completion of the trial. “Initially it (the HIV vaccine) will give 75% protection. At the
end of the research, it will be 100%, hence there is no harm” (44). In one study,
participants ascertained that all women should be vaccinated with HIV vaccine along
with drivers and sweepers, children, own risk behavior sex workers and couples. In terms
of personal benefits the percentage of respondents showed much higher for those who
32
were looking for prevention than those who were looking for better treatment or higher
quality care or free medication.
6.1.2. Social Benefits 57%
All the seven studies contributed to this theme. Contributing for the common cause of the
society as well as enhancing the progress of the scientific and medical knowledge
inspired many respondents to participate in a clinical trial. A sense of responsibility
towards the humanity is among one of the compelling reasons a person participate in
clinical trial. Majority of the respondents were looking forward to be a part of the
research study for the betterment of mankind. “… Everyone has a responsibility to
participate in such matters, our community is not aware, we should bring them in level
with the rest, inform the” (42). Respondents also believe that holding responsibility for
others allows them to consider whether or not to participate in a trial. “Because we’re
here to help each other, that’s the main thing” (42). The finding in this theme is that, the
percentage of respondents to participate in a trial were almost double in cases for
preventive trial such as HIV vaccine trial in contrast with those trial the will enhance
science and medicine.
6.1.3. Generate extra income 30%
Four of the seven studies fitted into this theme. Respondents indicated that their
participation was influence by the offer of money as a means of incentives (41). One of
the respondents stated, “…. We want a written guarantee plus insurance policy. The
document should specify that, in the event of death (of the person after taking the
vaccine), his family would be given full support” (44). It is apparent that the participants
33
were seeking for monetary compensation to be included in the inform consent in the case
of events like serious adverse effect or adverse reaction that may lead to dead.
6.1.4. Knowledge associated with the trial 54%
Three out of the seven studies contributed to this theme. Informing the potential risk that
may occur during the trial and being well informed about the procedure could tender
potential participants to participate in the clinical trial. Respondents agree that the manner
in which the trial staff provides information can give them the confidence to participate.
In one of the HIV vaccine trial respondents were willing to participate if they are given
assurance that the experimental vaccine trial would be safe and effective to conduct on
human.
6.1.5. Motivating Methods for Participation 32%:
Three out of the seven studies contributed to this theme. Respondents were more willing
to participate if the clinical trial information was provided by the government owned
television channel. Similarly some respondents also preferred newspaper and healthcare
providers regarding the information about clinical trials. Education was also a factor that
could persuade people participate in a clinical trial. Other potential motivating factors
that could contribute to participation in a clinical trial include TV, radio, magazines,
newspapers, internet, Harris Interactive, advocacy group and family/friends. The success
story of polio vaccination conducted by the government has also made respondents
confident that HIV vaccine would similarly have a great impact on the society.
34
6.1.6. Physicians 47%
Five out of the seven studies contributed to this theme. Most studies cited that their
family physician/general practitioners held a high esteem and considered participating in
a trial if they are encourage doing so. “I have been taught this is a noble profession. And
the ethics of the profession of converse, as you know, converse life, and I would never
even dream of suspecting a doctor, I wouldn’t” (42).
6.2. Barriers to participate in clinical trials
Table3. Barriers to participation in clinical trials
Logistical problem and misconception
Concern about the treatment
Fear Confidentiality issues
Psychosocial factors
Mistrust towards trial sponsors
Uncertainties Not willing unless I knew I was getting the vaccine
Unknown long-term side effects-uncomfortable
Effect on insurance, marriage or getting a job
Couple disharmony
Are like guinea pigs
Effect on travel Comfortable if I knew the vaccine is powerful enough
Fear of injection Lack of privacy at home
Social support
Worry about mode of treatment i.e. whether given vaccine or placebo
Time constraint Comfortable if I knew how it would affect my life
Long-term effect of vaccine
Privacy concerns
Peer family pressure
Are taking a gamble with their health
Not able to make independent decision
Do not want to interrupt treatment
Concern about safety procedure
Difficult to decide in anticipation
Do not want to take drugs without treating doctors permission
Lack of knowledge
Did not want to take new drugs
Side effects Lack of empowermen
35
6.2.1. Logistical problem and misconception 18%
Five out of seven studies contributed to this theme. This theme emphasized on the
difficulties and challenges for participating in a clinical trial. Some of the difficulties
participants often face is travelling long distance, busy lifestyle, and understanding
inform consent and other logistical problem. Respondents were also afraid that they will
be stigmatized for participating in a trial even if they do not have the disease.
6.2.2. Concern about the treatment 33%
Three out of the seven studies contributed to this theme. Respondents gave different view
concerning about the treatment they will be undergoing which let to certain barriers for
them to participate, In a HIV vaccine trial participants were afraid whether they will
receive a vaccine or a placebo and therefore refused to participate. Respondents also did
t: issue of male involvement.
Did not understand
Afraid of test Lack of supportive network/family commitments
Busy lifestyles Too much blood already withdrawn
Language Concern about drug side-effects
Migrant workers Cultural issue pertaining to gender
Asymptomatic/no disease
Stigma 18% 33% 19% 16% 11% 24%
36
not want to be involved in a new treatment because it would interrupt in their current
treatment, similarly some respondents simply did not want to participate because they did
not want to start new treatment. Concerns about the trial treatment were also felt on old
people and others who are on multiple drugs because of the fear of drug-drug
interactions, “Personally only because of my health, because I’m on other medication and
I think that might affect it…. It might react adversely to the drug I’m taking so many that
would be another reason why I personally wouldn’t do it” (42).
6.2.3. Fear19%
Six out of seven studies contributed to this theme. The fear of participating in a clinical
trial is clearly visible on a lot of aspects. Some people simply ignore to participate
because of the fear of injection. Respondents were more likely to voice their opinion
regarding safety and effectiveness of the trial with regards to possible side effects,
adverse reaction and safety procedure. For instance, in some of the government settings
people are afraid of the syringes and other tools that will be used during the procedure.
6.2.4. Confidentiality issue 16%
Three out of the seven studies included in this theme. Privacy remains another factor
where respondents gave as a reason for not participating in a clinical trial. Respondents
felt that it was important to safeguard the privacy or it will affect in their marriage,
employment and insurance. Potential participants in HIV vaccine trial were highly
concerned about the confidentiality of their personal information because people are
aware that HIV/AIDS is not just an ordinary disease. Similarly respondents pointed out
that there is lack of privacy at home which concerns them to enroll in a trial.
37
6.2.5. Psychosocial factors 11%
The factors associated with regards to psychosocial issues include lack of empowerment,
social support, couple disharmony, peer family and difficult to decide in anticipation etc.
“cannot come alone”, “Do not have knowledge, will ask husband...”, “Has to see what
husband says…”, “Husband will scold…”, “Husband may have doubt”, “can come if a
friend comes” (41). It is apparent that most Indian people lack the confidence to take
decision on their own and seems to rely on family or spouse. This aspect on clinical trial
participation is no different. They have this feeling of fear towards taking an independent
decision. Even though they have given a thought of participating, they are not able to
answer whether to participate in a trial or not.
6.2.6 Mistrust towards trial sponsors 24%
Four out of the seven studies contributed to this theme. Respondents felt that they would
be treated as guinea pigs after making personal inferences about the trial. They also
feared of receiving placebo which would not benefit their health at all and therefore
indicated their mistrust towards the organization on how the trial would be conducted. It
was also apparent that the patient would refer to their family doctors to give them advice
relating to participation in the trial, thus showing their mistrust towards the organization.
38
7. DISCUSISION The systematic review was performed by retrieving, selecting and analyzing the qualitative dates
of the studies to evaluate the factors that contribute to the factors affecting clinical trial
participation among the Indian subjects. The purpose of conducting systematic review is
important because evaluating Indian subjects on factors associated with participation will
provide better picture of the subject’s mindset on what determines their decision to participate or
not to participate in a clinical trial. The evaluation was carried out by two broad categories where
specific themes were identified for different factors; factors that favor participation and factors
that limit participation. The themes in factors favoring participation include personal benefits,
social benefits; generate extra income, knowledge associated with the trial, motivating methods
for participation and physicians. While the themes included in factors restricting participation are
logistical problems and misconception, concern about the treatment, confidentiality issue,
psychosocial factors and mistrust towards the sponsors. The contributing factors were allocated
on specific themes wherever it is associated and a percentage was calculated for each theme. The
purpose of calculating the percentage is to highlight which theme needs more attention for any
rectification either to encourage participation or eliminate barriers.
The study was primarily focused on Indian population because of the following reasons: 1. India
has become one of the hotspot for conducting global trials. 2. The availability of huge and
diverse population is favorable for implementing clinical trials because it enhances the rate of
enrollment. 3. Indian population (racial and ethnic group) has a unique ways of interpreting and
making a decision to participate in a clinical trial. Therefore it is important to understand the
factors the influences their decision to participate in a clinical trial.
39
The result shows that Indian people were more willing (prevalence-37%) to participate in a
clinical trial if they are provided with healthcare benefits. In almost all the major ethnic group it
has been confirms that personal benefits influences people to participate in a clinical trial (47).
Participants who were involved in HIV vaccine trial thought that, they will be protected from
HIV infection by participating in the trial. They believed that HIV is preventable by taking HIV
vaccine similar to polio vaccine (40). Personal benefit can take various forms such as free
medication, high quality care, better treatment, possible protection through vaccine trial and
possible cure by trial intervention. Personal benefits for relatives or family members are also
valued while considering participation in a trial. “…if it makes their life better and she’s going to
make the Chapatis again the yes they’ll sign it (consent form) (42). Some participants also felt
that the disparity between the couples could also be due to their desire to protect itself from the
fear of infection. “We may be unaware of the behavior of the men folk. If they had gone astray,
there are chances of us also to get infected. By taking the vaccine, this can be prevented” (44). In
a similar way, participating in the HIV Vaccine trial would benefit personally as well as to their
spouse. A strong affection towards the family members also contributes in participating in a
clinical trial provided the research would benefit them, “My son was born with a hole in his
heart and were constantly in and out for the first year and the hospital asked me if I could put my
child forward for the student’s exams and assessments” (42). By benefitting his family, he
benefits himself from the trial because he has executed his strong sense of responsibility. One
male respondent with H. pylori was very much willing to participate if the trial could cure his
indigestion. “Well they asked me and I said, ‘why not? Go for it’, because the main reason was I
used to have indigestion, and I wanted to find out why do I have indigestion…so I thought if it’ll
cure, if they can find out why not have a go and have a trial, that was the main reason” (42).
40
Earlier studies showed that people participate in clinical trial for personal benefits due to the
non-availability of medicine (42, 48). However it has broader issues now such as cultural factors,
socio-economic factors and healthcare conditions that are predominant in the country. For
example, people from lower economic background are attracted and influence to participate in a
clinical trial by the offering of free medical treatment and other benefits.
On the other hand 57% of the respondents were willing to participate for the common cause of
social welfare and to advance science and medicine. This shows that not only they want to get
cured but they also want others to get cured, thus showing goodwill for the society and science.
In one study, an overwhelming 98% of the participants agreed that participating in a HIV
Vaccine Trial will benefit for the common good of India (40). People also participate in clinical
trial for the advancement of medicine and science. Respondents also felt a sense of pride in
themselves indicating their desire to contribute for the society. “I fell glad to take social risk”,
“Do something that is good for the world” (41). Respondents from HIV Vaccine trial stress that
participating in such trial would benefit the society and stop HIV infection. “Helping to find a
vaccine that works”, “helping to stop the epidemic” (40). However respondents were also
optimistic that their participation would directly impact the current scenario. Nevertheless they
were more willing to participate for their children and the future generation. “We should not
think that something does not benefit us now and why should we participate, humans should not
think like this if it has not benefited my generation but the third generation it may benefit them,
then I should take a part” (42). The evidence of altruistic motivation can also be seen when
healthy volunteers participate in clinical trial. However, in contrast to other respondents,
41
respondents from HIV vaccine trial had more intend, almost triple the percentage to participate
as a selfless wish to benefit the society (41-46).
The result also shows that Indian people rely on physician (37%) while taking decision to
participate in a clinical trial. The physicians are considered as health guide among the Indian
population and people hold them high esteem believing that they will never misguide them.
Therefore if a physician tells or advice them to participate in a clinical trial, it is highly unlikely
to refuse them. It is apparent that the doctors have a great impact on the decision-making process
in the Indian culture. They think that doctors will only do good and will be responsible to
safeguard the health of a patient. Various studies have pointed out the roles of physician in
patient recruitment through recommendation, encouragement and other means of communication
(48-52). There is a well known fact that the relationship between a doctor and a physician is
unequal and the patients tend to go by the doctors judgment. They fear that refusal to participate
in a trial as referred by their physician would affect them to gain access to medical care.
Generating extra income also remains a significant theme in this study where patient’s health is
put to unnecessary risk for the sake of monetary gain. In a country such as India where poverty is
apparent it is highly likely that money could be an influence to their participation. It is important
to understand their judgment on the likes of monetary and other incentives influencing in their
participation.
This systematic review also showed that understanding the detailed knowledge about the trial
such as objectives and procedures enhances the chances of subject participation. Education is one
42
of the issue that many people raised in the HIV vaccine trial as cited by one of the respondents
“community members would want to know about the frequency of the vaccine and the site
administered, how it might impact marriage, how long the HIV positive result will last, how long
will the vaccine protected for, and will the vaccine be effective” (44). In one study, majority of
the participants understood that the research study is voluntary and they were also aware of the
risk involved in the study (43). It was also apparent, that respondents showed greater willingness
to participate by understanding the use of the vaccine and efforts that are being made for vaccine
development. “The ELIZA test will be positive due to vaccination. We should tell those persons
who had taken the vaccines that the positivity would disappear after some time” and “If we go
separately to the doctors and get tested, there will not be any problems. When the husband and
wife go together, there will be a problem due to the positive result” (44). The respondents wanted
to understand the concept of HIV vaccine trial like duration of protection, site of administration
and effectiveness of the HIV vaccine trial. Most of the participants felt that the terminologist
were major concern to understand the concept of the trial and preferred simple information. “I
understand bits of it, some things I didn’t understand. The second time I went I took my daughter
with me. She explained what he said and that they will offer to get somebody to translate for me.
When I visit the doctor I occasionally take my daughter because of the terminology used” (42).
This indicates that languages, trial staff attitude and terminology could all play an important role
in enrolling the potential participants. If there is any misconception about the trial the potential
participants are made proper understanding through constant verbal explanation. In any case,
lack of knowledge about the trial could lead to possible non-participation. At the same time
providing incomplete information or hiding information would be violating the ethical conduct
of the clinical trial.
43
Moreover, motivating factors like TV, advertisement, newspaper, radio, awareness campaign
also enhances the rate of recruitment by educating and clarifying any misconception that may
prevail among the people. Participants felt that the government will never do wrong and wants
the government to handle HIV vaccine trial. “If it is done through the government, many people
could come forward to take it”. “…the government is never wrong. Therefore, if the government
endorses a vaccine, it will surely be safe. So we can take the vaccine without fear” (44). The
respondents also suggested that the researchers should informed the future HIV vaccine trial as
quoted by one of the respondents “being HIV positive is a part of the vaccine trial and be so
declared, if necessary” (44). Potential participants consider the importance of healthcare camps
that are emphasized on trial-related information. “We have a good community spirit at the
Mandir and sometimes they organize specialists to come in so we can talk about our health
problems. If they talk about clinical trials and medical research I think many people would take
an interest and be willing to participate” (42). To sum up, factors such as personal benefits,
altruism and monetary could play a role in the decision making process of the individual while
themes like physician and knowledge of the trial indicates that physician do play a major role in
recruitment. Therefore it is extremely important that physician involving in recruitment plan
should be properly trained and possesses all the required knowledge about the trial.
Although respondents indicated their trust towards physicians, distrust towards researchers and
physicians were also expressed as one of the barriers (24%) by the respondents. Factors such as
fear of receiving placebo, the idea of treating as guinea pigs, distrust in clinical research have
shown as a negative impact towards the subjects thus indicating as barriers to their participation.
44
The differences in trust and mistrust by the respondents towards the physician and researchers
could be due to previous experiences in clinical trial, literacy and ethnic variation (53, 54). It is
therefore important to promote trust and identify the source of mistrust within the trial
organization to enhance trust among the potential subjects.
Respondents also indicated fear such as side-effects, afraid of test and injection, safety and
efficacy issue as major barriers for them to participate in a trial. In a HIV vaccine trial
respondents fear that they might be infected with HIV while participating in the trial. “Feel fear
of getting other disease…”. “I might get AIDS” (41). Respondents were not willing to
participate unless they are guaranteed that participating in the trial would not lead to long-term
side effect. “…But guarantee that there’s going to be no harm to yourselves or whatever, you
know, there’s not going to be any reaction…. That’s why you are researching, so you are using
them as a form of guinea pig to be honest. You know, so there will be reaction and I wouldn’t be
impressed with that” (42).
Subjects participating in a clinical trial involve a lot of commitment to ensure that they follow
the procedure as per the protocol. However, the daily routine of life could impact their daily
routine of lifestyle which in some cases might be unavoidable and could jeopardize their
involvement in the trial even if they are willing to participate. “Because of time I cannot enroll”.
“Have work ... will go to Nepal” (41). For instance there could be travelling burden, busy
lifestyle, time constraint etc (41, 40). Lack of knowledge about the trial is also a factor in which
many participants opt out to participate. Some respondents lack decision making fearing that the
studies could not be decided on what will happen to their future. In one of the study that was
45
conducted in the UK, the South Asian participants felt that the inability to speak English was a
major barrier to participate in a trial.”...because of the language barrier and because the majority
of South Asian people that I see are women, I feel sometimes that there is little bit of a barrier”
(42). The complicated nature of filling up the inform consent makes the potential participants
difficult to decide. “… I think sometimes the official form is a bit threatening to people, they
think because they got this written form they’ve got to sign…. And sometimes I think that makes
people nervous, because they think, ‘God this must be something really big if I’ve to do this. I
get asked about all sort of things and I don’t have to do this’… and that’s sometimes a bit scary
for people, I think” (42). In Indian culture people believe that male are more dominant and
women often find it hard to make a decision of their own which was regarded as one of the
frequent barriers among women to participate in a trial. “Husband should be given first” (41).
Misconception needs to be assessed by educating the potential participants in a way that will
make them understand completely so that they take a proper decision accordingly. Trial burden
such as busy lifestyle and travelling burden also adds to their barriers. Reducing this entire
burden would make trial participation in India a lot easier and faster.
In addition to this, confidentiality issue also contributes to the barrier in participation which is
considered as an important concern. The subjects seek for integrity at any costs and therefore
their privacy must be acknowledge and considered. A number of respondents also shared their
concern about the involvement of family, spouse and peers while making a decision to
participate. It is Indian culture to discuss health related issues with their family and peers
contradicting the US cultures where the doctors never discloses health issues with family or
friends other than the patient itself. In India cultural barrier is a common phenomenon which
46
needs proper attention for rectification. Language has also been identified as common barriers
among South Asian particularly Indians living in the UK and US. Several measures were used to
overcome language hurdles by introducing translators. However due to the lack of technical
terms and complicated nature of clinical trial concept it adds further burden to solve such forms
of barriers. The only way to introduce translators is to train the translators about clinical trial
concept.
The overall study was not very satisfactory because the reviewer could not include some
important elements such as population-based surveys and other external validity which would
have evaluated more dimensions regarding the contributing factors of trial participation. The
respondent’s age group was not mention in three studies while four studies did not mention the
ma/female ratio. This could have an impact on determining the specific demography that needs
to be evaluated. Statistical heterogeneity was also observed across the themes. This led to weaker
inferences about the estimates of overall effect. There was inconsistency among the study results
which made it difficult to interpret the results of the systematic review. Two of the studies with
focus group discussion did not provide data’s to be included in the statistical analysis which
limited the strength of the conclusions. Since it was an individual thesis, independent data
reviewer was not available which limited the reviewer in assessing the validity of the included
studies.
In some cases, relevant articles which the reviewer thought might be eligible to be included for
the final analysis could not be either access or full text not available. One study included in the
final analysis was unpublished studies. The result of the survey was presented in one of the
47
conference held in ICRI, Mumbai. However, the inclusion of this data was not influence by any
source of bias rather the reviewer considered the data authentic for final analysis and would be
justifiable as an exception to the inclusion criteria. In a diverse country such as India with a
variety of cultural heritages, religious beliefs and ethnicities the result may vary with different
groups of people.
48
8. CONCLUSION This systematic review solely focuses on subject participation in clinical trial within the
Indian population by evaluating the factors that either favors or hinders participation.
India has a great potential for and prospects for future clinical trial and it is essential to
take appropriate measures for future planning. It is important that research studies heeds
to be conducted to understand the clear mindset of the people from different ethnic
groups and cultural backgrounds. Researchers should employ more multi-recruitment
strategies in their approach. The demographic and social profile of the Indian population
should be defined for better implementation. Educating patient through various means
such as awareness campaign and effective media will help to enable and promote trust
towards people and enhance large better enrollment frequency. It is evident from the past
study that informed consent was not exercise appropriately and therefore needs to be
improved. More emphasis should be given to the potential participants on medical
attention rather than personal benefits. In order to assure subjects safety and confidence it
is also important to assure them about the presence of data safety and monitoring board.
This will further help in establishing trust with the participants. Assurance of keeping
confidentiality is also necessary from the perspective of study subjects and needs to be
respected. India possesses tremendous doctors and researchers who need to be trained
properly about all the necessary knowledge of clinical trial so that all the participants are
enrolled ethically.
The government should involve more in its participation and set up a proper structure to
regulate the conduct of clinical trial before promoting India as a global clinical trial sites.
49
Potential trial participants are very vulnerable to entering clinical trial with the lure of
obtaining healthcare or generating extra monetary possibly overlooking the risk involve
in their participation. India at present needs urgent action to counter enrolling participants
unethically so that the rights and integrity of the subjects are protected.
50
9. REFERENCES
1. B. Hirschhorn, Understanding the Development of the Clinical Study Budget While
Avoiding Bumps and Pitfalls. Presentation at The Office of Clinical Trials Workshop. 15 January 2004. http://http://www.research.temple.edu/oct/
2. V. Sanghavi, U. Sahoo, A. Bhatt, "Challenge of Patient Recruitment and Retention: Critical Role of Clinical Research Coordinator," http://Pharmabiz.com/ (8 July 2004). http://http://www.pharmabiz.com/article/detnews.asp?articleid=22867§ionid=50
3. Surinder Singh, Drugs Controller General of India, at a conference of the Institute of Clinical Research (India), Mumbai, October 10-11, 2008.
4. Tufts Centre for Study Drug Development. Food Drug Law Journal 2002 5. Clarke, M. Systematic reviews and the Cochrane Collaboration. Available at:
www.cochrane.org/docs/whycc.htm 6. Cutting Edge information, Accelerating Clinical Trials: Budgets, patient recruitment and
productivity, May 2004 7. New Approaches to Patient Recruitment, ARCP White paper, 2002 8. Schilsky, RL. Conversations in Care - Chapter 7, Meeting the Challenges of Clinical
Trial Enrollment. Web-book. http://www.conversations incaes.com/ web_book/chapter07.html. Viewed 16 April 2003.
9. Barriers to Clinical Trial Enrollment-National Cancer Institute, www.cancer.gov/clinical trials/developments.
10. Presentation by Dan Mcdonald, vice president, business development, Excel Life Sciences, at a meeting of the Institute of Clinical Research (India), Mumbai, October 10-11, 2008.
11. Ellis PM: Attitudes towards and participation in randomized clinical trials in oncology: a review of the literature. Ann Oncol 2000, 11(8):939-945.
12. Cox K, McGarry J: Why patients don't take part in cancer clinical trials: an overview of the literature. European journal of cancer care 2003, 12(2):114-122.
13. Tournoux C, Katsahian S, Chevret S, Levy V: Factors influencing inclusion of patients with malignancies in clinical trials. Cancer 2006, 106(2):258-270.
14. Mills EJ, Seely D, Rachlis B, Griffith L, Wu P, Wilson K, Ellis P, Wright JR: Barriers to participation in clinical trials of cancer: a meta-analysis and systematic review of patient-reported factors. The Lancet Oncology 2006, 7(2):141-148.
15. Langley C, Gray S, Selley S, Bowie C, Price C: Clinicians' attitudes to recruitment to randomised trials in cancer care: a qualitative study. Journal of health services research & policy 2000, 5(3):164-169.
16. Jones JM, Nyhof-Young J, Moric J, Friedman A, Wells W, Catton P: Identifying motivations and barriers to patient participation in clinical trials. J Cancer Educ 2006, 21(4):237-242.
17. Grunfeld E, Zitzelsberger L, Coristine M, Aspelund F: Barriers and facilitators to enrollment in cancer clinical trials: qualitative study of the perspectives of clinical research associates. Cancer 2002, 95(7):1577-1583.
51
18. Gaul C, Schmidt T, Helm J, Hoyer H, Haerting J: [Motivation and barriers to participation in clinical trials]. Med Klin (Munich) 2006, 101(11):873-879.
19. Wallace K, Fleshner N, Jewett M, Basiuk J, Crook J (2006) Impact of a multidisciplinary patient education session on accrual to a difficult clinical trial: the Toronto experience with the surgical prostatectomy versus interstitial radiation intervention trial. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 24: 4158–4162.
20. Palmas W, Teresi J, Morin P, Wolff LT, Field L, et al. (2006) Recruitment and enrollment of rural and urban medically underserved elderly into a randomized trial of telemedicine case management for diabetes care. Telemedicine Journal and E-Health: The Official Journal of the American Telemedicine Association 12: 601–607.
21. Unson CG, Ohannessian C, Kenyon L, Case A, Reisine S, et al. (2004) Barriers to eligibility and enrollment among older women in a clinical trial on osteoporosis: effects of ethnicity and SES. Journal of Aging and Health 16: 426–443.
22. Lara PN, Higdon R, Lim N, Kwan K, Tanaka M, et al. (2001) Prospective evaluation of cancer clinical trial accrual patterns: identifying potential barriers to enrollment. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 19: 1728–1733.
23. King WD, Defreitas D, Smith K, Andersen J, Perry LP, et al. (2007) Attitudes and perceptions of AIDS clinical trials group site coordinators on HIV clinical trial recruitment and retention: a descriptive study. AIDS Patient Care and STDs 21: 551–563.
24. Shaw PH, Ritchey AK (2007) Different rates of clinical trial enrollment between adolescents and young adults aged 15 to 22 years old and children under 15 years old with cancer at a children’s hospital. Journal of Pediatric Hematology/ Oncology: Official Journal of the American Society of Pediatric Hematology/ Oncology 29: 811–814.
25. Wood CG, Wei SJ, Hampshire MK, Devine PA, Metz JM (Dec 2006).The influence of race on the attitudes of radiation oncology patients towards clinical trial enrollment. Am J Clin Oncol 29: 593–599.
26. Buchbinder SP, Metch B, Holte SE, Scheer S, Coletti A, et al. (2004) Determinants of enrollment in a preventive HIV vaccine trial: hypothetical versus actual willingness and barriers to participation. Journal of Acquired Immune Deficiency Syndromes (1999) 36: 604–612.
27. Cambron JA (2001) Recruitment and accrual of women in a randomized controlled trial of spinal manipulation. Journal of Manipulative and Physiological Therapeutics 24: 79–83.
28. Mapstone JED, Roberts IG: Strategies to improve recruitment to research studies. Cochrane Database of Systematic Reviews 2004:MR000013.
29. Recruitment for controlled clinical trials: literature summary and annotated bibliography. Controlled clinical trials 1997, 18(4):328-352.
30. Campbell MK, Snowdon C, Francis D, Elbourne D, McDonald AM, Knight R, Entwistle V, Garcia J, Roberts I, Grant A: Recruitment to randomised trials: strategies for trial enrollment and participation study. The STEPS study. Health technology assessment (Winchester, England) 2007, 11(48):iii. ix-105
31. Prescott RJ, Counsell CE, Gillespie WJ, Grant AM, Russell IT, Kiauka S, Colthart IR, Ross S, Shepherd SM, Russell D: Factors that limit the quality, number and progress of
52
randomised controlled trials. Health technology assessment (Winchester, England) 1999, 3(20):1-143.
32. Watson JM, Torgerson DJ: Increasing recruitment to randomized trials: a review of randomised controlled trials. BMC medical research methodology 2006, 6:34.
33. Fayter D, McDaid C, Eastwood A: A systematic review highlights threats to validity in studies of barriers to cancer trial participation. Journal of clinical epidemiology 2007, 60(10):990-1001.
34. Mc Daid C, Hodges Z, Fayter D, Stirk L, Eastwood A: Increasing participation of cancer patients in randomised controlled trials: a systematic review. Trials 2006, 7:16.
35. Tomlinson H (2004) Drugs giant moves trials abroad: Glaxo lured by security and low costs of trials overseas. Guardian.co.uk.
36. Joseph J (2008) Entering the contract research industry in India. Contemporary Clinical Trials 29: 311–313.
37. Cyberlaw Candice Player: Outsourcing Clinical Trials to India. Berkman http://cyber.law.harvard.edu/cyberlaw2005/Candice_Player:_Outsourcing_ Clinical_Trials_to_India.
38. Don M Clinical trials and safety reporting under Schedule Y. Pharmabiz.com. 39. Nundy S, Chir M, Gulathi CM (2005) A New Colonialism? — Conducting Clinical
Trials in India. N Engl J Med 352: 1633–1636. 40. Suhadev M, Nyamathi AM, Swaminathan S, Venkatesan P, Sakthivel MR, et al. (2006)
A pilot study on willingness to participate in future preventive HIV vaccine trials. Indian J Med Res 124: 631–640.
41. Sahay S, Mehendale S, Sane S, Brahme R, Brown A, et al. (2005) Correlates of HIV vaccine trial participation: an Indian perspective. Vaccine 23: 1351–1358.
42. Hussain-Gambles M, Leese B, Atkin K, Brown J, Mason S, et al. (2004) Involving South Asian patients in clinical trials. Health Technology Assessment (Winchester, England) 8: iii, 1–109-iii, 101-109.
43. Harris Interactive (2005) Participation in Clinical Trials Lower in Europe and India than in the United States. Harris Interactive studies public perceptions of clinical trials in six European countries and India. Healthcare News 5.
44. Nyamathi AM, Suhadev M, Swaminathan S, Fahey JL (2007) Perceptions of a community sample about participation in future HIV vaccine trials in south India. AIDS and Behavior 11: 619–627.
45. B Gitanjali, R Raveendran, DG Pandian, S Sujindra (2003) Recruitment of subjects for clinical trials after informed consent: does gender and educational status make a difference? JPGM: 109-13
46. A survey on patient participation in clinical trial: presentation by Dan McDonald, Vice-President, Business Development, Excel Life Science at a meeting of the ICRI(Institute of Clinical Research, India), Mumbai, October 10-11, 2008
47. Roberson NL (1994) Clinical trial participation. Viewpoints from racial/ethnic groups. Cancer 74: 2687–2691.
48. Tu S-P, Chen H, Chen A, Lim J, May S, et al. (2005) Clinical trials: understanding and perceptions of female Chinese-American cancer patients. Cancer 104: 2999–3005.
49. Catania C, DP T, Goldhirsch A, Radice D, Adamoli L, and Medici M, et al. (2008) Participation in clinical trials as viewed by the patient: understanding cultural and emotional aspects which influence choice. Oncology 74: 177–187.
53
50. Khaliq W, Gross M, Thyagarajan B, Jones-Webb R (2003) what motivates minorities to participate in research? Minnesota Medicine 86: 39–42.
51. Mills EJ, Seely D, Rachlis B, Griffith L, Wu P, et al. (2006) Barriers to participation in clinical trials of cancer: a meta-analysis and systematic review of patient-reported factors. The Lancet Oncology 7: 141–148.
52. Avis NE, Smith KW, Link CL, Hortobagyi GN, Rivera E (2006) Factors associated with participation in breast cancer treatment clinical trials. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 24: 1860–1867.
53. Murthy VH, Krumholz HM, Gross CP (2004) Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA: The Journal of the American Medical Association 291: 2720–2726.
54. Ellington L, Wahab S, Sahami Martin S, Field R, Mooney KH (2006) Factors that influence Spanish- and English-speaking participants’ decision to enroll in cancer randomized clinical trials. Psycho-Oncology 15: 273–284.
