|Year : 2016 | Volume
| Issue : 1 | Page : 174-177
Barriers in conducting clinical trials in oncology in the developing world: A cross-sectional survey of oncologists
M Dandekar1, R Trivedi1, N Irawati1, K Prabhash2, S Gupta2, JP Agarwal3, AK D’Cruz1
1 Department of Head Neck Surgical Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
2 Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
3 Department of Radiation Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India
|Date of Web Publication||28-Apr-2016|
A K D’Cruz
Department of Head Neck Surgical Oncology, Tata Memorial Centre, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Several obstacles impede oncologists from performing clinical trials in the developing world. This study aimed to identify these barriers in order of importance and suggest possible remedial measures. Materials and Methods: Design – cross-sectional survey. Two part questionnaire capturing experience of oncologists in practice and conducting trials (Part 1) and perceived barriers pertaining to investigator (training, time), patient (strict follow-up protocol), infrastructure (funds) and professional environment (encouragement from seniors) (Part 2) were administered to oncologists in two different settings: (1) Online portal (Survey Monkey) (2) In person during a national conference (Best of American Society of Clinical Oncology). Responses were captured on a Likert scale (1–5). Results:(436/3021) 14.04% responded. A total of 313 (71.8%) had experience in conducting trials, but these were mainly industry-sponsored or small nonpractice changing studies. Lack of patient follow-up was the most significant barrier (inter quartile range [IQR] 4–5) followed by inadequate training, time and funds (IQR 2–5) and lack of encouragement (IQR 2–4) in decreasing order of frequency. Lack of adequate training was a barrier across all specialties (113 [71.97%] radiation oncologists, 71 [60.68%] medical oncologists and 73 [71.56%] surgical oncologists). More than half of the respondents without experience in clinical trials worked in academic institutions (50.48%). They perceived time constraint as a barrier more than their counterparts into private practice (175/242 [72.31%] vs. 119/177 [66.47%] respectively). Conclusion: Inability to maintain patient follow-up, lack of protected time and funds, inadequate training were the most significant barriers. Most of these can be addressed.
Keywords: Cancer, evidence-based medicine, questionnaire, randomized controlled trial, survey
|How to cite this article:|
Dandekar M, Trivedi R, Irawati N, Prabhash K, Gupta S, Agarwal J P, D’Cruz A K. Barriers in conducting clinical trials in oncology in the developing world: A cross-sectional survey of oncologists. Indian J Cancer 2016;53:174-7
|How to cite this URL:|
Dandekar M, Trivedi R, Irawati N, Prabhash K, Gupta S, Agarwal J P, D’Cruz A K. Barriers in conducting clinical trials in oncology in the developing world: A cross-sectional survey of oncologists. Indian J Cancer [serial online] 2016 [cited 2019 Aug 25];53:174-7. Available from: http://www.indianjcancer.com/text.asp?2016/53/1/174/180865
| » Introduction|| |
Well-conducted randomized controlled trials (RCT) form the highest level of evidence and the backbone of evidence-based framework. Low and middle income countries (LMIC) like India have well-qualified medical professionals, good infrastructure, large patient volumes, low overheads as well as unique disease patterns and should ideally be important players in contributing to oncological research. However, often the motivation of oncologists to perform trials is impeded by several real or perceived obstacles.
This study was initiated to help identify barriers for the conduct of clinical trials in the field of oncology and establish possible remedial measures. There is sparse information on this subject from the developing world. It was felt that results of this study could be used to motivate doctors from similar resource settings across the world toward conduct of research as well as identify issues that may need to be addressed by policy makers.
| » Materials and Methods|| |
The study involved a questionnaire based survey directed at oncologists from the major specialties (medical, surgical and radiation) and backgrounds (academic and private practice) which was conducted over a 2-month period.
Development of questionnaire
A comprehensive search of published literature on barriers in conduct of clinical trials was performed using PubMed and Google Scholar. Barriers, clinical trials, hindrances and research were used as keywords in various combinations. A list of relevant articles was identified along with relevant cross references. Literature was reviewed, and an exhaustive preliminary list of relevant questions was prepared by the first and corresponding authors who were surgical oncologists (MD and AKD). This was discussed with the other authors who were specialists from other fields namely medical and radiation oncology (SG, KP, JPA,) to give a balanced multidisciplinary coverage and applicability across all specialties of oncology. The questions were then finalized with two broad aims in mind:
- To incorporate relevant as well as remediable barriers to conducting clinical trials
- To address barriers specifically pertaining to the developing world.
The final questionnaire was formulated in 2 parts. Part 1 consisted of profile of respondents and experience in conducting clinical trials. Part 2 consisted of questions pertaining to barriers in conducting trials. Potential barriers were grouped as those related to investigator (training, time), patient (reluctance to abide by strict follow-up protocol), infrastructure (funds) and working professional environment (encouragement from seniors).
A pilot survey was conducted among senior fellows and faculty members of the authors' institution (n = 30). Comprehensibility and ease of completing the questionnaire were considered. Suggested changes from respondents were rediscussed among authors and incorporated into the final questionnaire.
Final questionnaire is as per Appendix 1.[Additional file 1]
Questionnaire was administered among oncologists in two different settings:
Initial survey was initiated via an online portal (Main website: www.surveymonkey.com; Company: Survey Monkey Inc.; Location: Palo Alto, California, USA). All nonrespondents received reminders every week for a month (four reminders) to ensure better response rates. To enhance the number of responses and get wider representation, the questionnaire was also served in person to oncologists attending the Best of American Society of Clinical Oncology (ASCO) meeting. The Indian meeting provides an opportunity to showcase research work done by Indian oncologists presented at ASCO. It was felt that the delegates would be the true representatives of oncologists who would have the potential and infrastructure for conduct of clinical trials from within the country.
Confidentiality was maintained in order to ensure genuine responses.
Database of oncologists
A comprehensive list was made by obtaining details of oncologists from all national oncology associations by contacting the office bearers of various associations. This comprised of majority of specialized oncologists in India working in diverse professional settings (teaching hospital, independent practice, etc.) ensuring fair representation from all stakeholders.
Data were maintained in Statistical Package for the Social Studies (SPSS) version 20 (IBM SPSS Statistics, Armonk, NY: IBM Corp). Majority of the analysis was descriptive.
Responses to barrier questions were obtained on a Likert-type scale from 1 to 5. The scale was graded from 1: Complete disagreement (not a barrier) to 5: Complete agreement with the statement (a barrier). A median barrier rating was calculated for each question along with interquartile range (IQR).
Correlation between the profile of respondents and barriers was made by cross tabulation.
| » Results|| |
A total of 3021 questionnaires were circulated. Of the151questionnaires distributed at the National Conference, 144 responded while of 2870 questionnaires sent through the online portal there were 292 respondents. The overall response rate was 14.04% (436 responses). The profile of respondents is tabulated [Table 1].
Belief about need of clinical trials in oncology practice
While 299/401 (74.5%) completely agreed that well-conducted trials can influence change in clinical practice, 102/401 (25.4%) of respondents did not reply assertively.
Involvement of respondents in trials
Totally, 313 (71.8%) had experience in conducting clinical trials, 52 (50.48%) of those without experience in conducting trials were from academic institutes.
Among those involved in clinical trials, 144 (34%) were principal investigators in multicentric, collaborative trials. A total of 63 (30.43%) of oncologists were involved in industry-sponsored trials. Totally, 148 (33.9%) participated in industry-sponsored trials just to gain experience in conducting trials.
[Table 2] tabulates the distribution of respondents based on the type of study.
Grading of barriers
The median and IQR for each question is tabulated [Table 3].
Patient reluctance to abide by a strict follow-up protocol was considered as the most significant barrier.
Investigator (training, time) and infrastructure (funds) related factors as barriers were rated equally.
Factor related to work environment (encouragement from seniors) was the least important.
Correlation of barriers to profile of respondents
Lack of adequate grooming to conduct clinical trials was a barrier across all oncological specialties (113 [71.97%] of radiation oncologists, 71 [60.68%] of medical oncologists and 73 [71.56%] of surgical oncologists).
Time constraint was perceived as a barrier among 175/242 (72.31%) in teaching institutes and 119/177 (66.47%) of those into private practice.
A total of 91/334 (27.24%) of those who considered patient factors to be a major hindrance and 69/262 (26.33%) of those who considered lack of funds to be a barrier had no experience in conducting clinical trials.
| » Discussion|| |
Practice of oncology is governed by evidence-based guidelines, of which the most widely followed are the National Comprehensive Cancer Network and European Society for Medical Oncology., These guidelines are formulated on trials predominantly conducted in the developed world. Results of these trials may not have global applicability particularly in LMIC given a different patient population, unique disease characteristics as well as available infrastructure and costs. In fact the large patient numbers, available medical expertise and low overheads could be an ideal environment for conduct of trials in LMIC to fill the information void and make invaluable contribution to World literature particularly for unique cancers such as oral cancers and cost-effective strategies that could have global applicability. Therefore, there is a need for developing nations to conduct clinical trials.
In our survey, among 194 oncologists who were Principal/Co investigators in RCT, a majority indicated that they were involved in investigator initiated studies (149 [76.8%]). This was however contrary to data from the Clinical Trials Registry-India (CTRI), Indian Council of Medical Research which maintains a registry of all trials conducted in India. The CTRI revealed only about 61 registered RCTs most of which were industry-sponsored (37/61; 61% RCTs; keyword: Oncology; n = 99). This establishes the fact that while investigators in countries like India conduct trials, these are obviously small, unregistered trials which are not practice defining. Understanding the reasons for this could help identify rectifiable measures and provide a conducive environment toward the conduct of RCTs.
The most significant barrier found in our study was the inability to maintain a meticulous follow-up of patients. In LMIC, limited availability of oncology based facilities makes it difficult for patients to travel long distances resulting in significant loss to follow-up. The CTRI suggests that < 10% of studies (375/4755) consider survival as an outcome that mandates a rigid follow-up regime. However, keeping with global economic development, the number of institutions dedicated to oncology is increasing. The performance of multicentric, collaborative studies would enable overcoming this hurdle with patients being treated in facilities close to home thus making follow-up easier. Additionally, using novel techniques such as harnessing the widespread Indian telecommunication network that is one of the largest, second only to China, could help in maintaining robust follow-up. Use of short messaging system should be particularly deliberated upon since a vast majority of patients have no permanent address thus precluding dependence on postal communication.
However, it is worth noting that 27% of those who responded affirmatively that follow was a major hindrance had no experience in conducting trials. Thus, this patient-related factor might be a perceived rather than a real hindrance. Moreover, there have been examples of well-conducted trials from this country where a stringent follow-up was possible.
Lack of time, training and funds were considered as hurdles in lesser order of importance.
Research outcomes from academic institutes are less than satisfactory borne out by the fact that more than half (50.48%) of those without experience in conducting trials were from academic institutes. The most plausible explanation would be that the majority of academic institutes are government funded, and doctors are inundated by large patient volumes and mandatory teaching activities leaving negligible time for research activities. Emphasis, therefore, must be made on “protected time” to make an atmosphere conducive for the conduct of research.
Increasing manpower support committed to clinical research could be a rectifiable measure to ensure protected time for clinicians. Furthermore, while governing bodies responsible for appraisal lay down emphasis on publications, much attention is paid on the number of publications without consideration of their quality (i.e. RCT vs. case reports and case series). Incentivizing good quality trials could act as a further impetus toward conduct of research.
Training in clinical trials was perceived as a hurdle across all specialties. This again is easily rectifiable by incorporating concepts of evidence-based medicine at the inception of medical training itself.
Finally, in our study, only about 21% (92) respondents strongly perceived lack of encouragement from peers and seniors as an obstacle toward conducting research. This is a heartening finding since changing mindsets and professional work environment would not be an immediate remediable task.
Our study is one of the few as well as the largest addressing this issue in this part of the world.
A response rate of 14% might appear inadequate but it would be worthwhile to mention that apart from the significant number of respondents (436), the profile of respondents is well-distributed across all specialties, experience as well as background of practice. Thus, the respondents of this survey can be considered to be a true representative of practicing oncologists from India. Nulty  in their review of determining adequacy of response rates to surveys suggested that even in stringent conditions (3% sampling error and 95% confidence interval), 25% response rate is adequate in a population of 2000 respondents. Thus, 14% response rate from a population of more than 3000 could be considered adequate. Another drawback of this study would be that the questionnaire was limited to few specific perceived barriers. Hence equally important issues like tedious process of acquiring regulatory approvals etc., were not touched upon. These were deliberately not considered as the focus of this survey was to establish barriers directly addressing clinicians' attitude. Moreover, issues pertaining to regulatory approvals before commencing clinical trials fall under the purview of the government and thus not remediable based on an oncology investigator's perspective.
| » Conclusion|| |
A large number of oncologists are inclined to performing clinical trials with a conducive professional environment. Obstacles do exist but are not unsurmountable. The most important barrier is inability to maintain a robust database due to significant loss to follow-up. This can be overcome by encouraging multicentric studies and using innovative methods at maintaining follow-up. Lack of funds, training and inadequate time are obstacles rated in lower order of importance. Measures to provide protected time and incentives for conducting trials in academic institutes, increasing availability of funds and inculcating evidence-based medicine at the inception of medical teaching would result into better research outcomes.
Authors declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.
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[Table 1], [Table 2], [Table 3]