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Trial participation or not
Globally, less than one percent of all physicians are ever involved in an industry-sponsored clinical trial. In the US alone, this figure has reduced from 8% to 3% during the past decades.
The reason so few physicians take part in sponsored trials is not exactly known. It is however known that some physicians are not at all interested in trial participation, while others are keen but are never invited. Some doctors are invited to participate but they hesitate, since they lack the knowledge about conducting a clinical trial and do not have research staff and/or administrative support. It has been reported that when doctors are invited to participate in an industry-sponsored clinical trial, between 10-20% respond positively.
So what are the incentives for a physician to participate in an industry-sponsored clinical trial? There are more general incentives valid for any clinical trial, and then there are trial-specific incentives. The general incentives to participate in clinical trials include free education and good experience for the site staff—effects which may eventually have a spin-off effect on other research projects. Sponsored trials will also generate an income for the site, and in some settings this extra revenue is used to conduct non-funded clinical research.
Positive and negative incentives
The trial-specific incentives are exemplified and discussed below. They should be addressed prior to accepting or rejecting trial participation. In general, US investigators are more critical in embarking on a sponsored trial, because they are requested to have a full understanding of the protocol, work load associated with the trial, and contractual and financial terms.
Incentives are the basis to make a choice – here to participate or reject trial participation. There are positive incentives and negative incentives. Positive incentives represent "rewards" and negative incentives can act as "penalties". The “rewards” should overweigh the “penalties” before moving ahead.
Only about 50% of clinical investigators will embark on a second industry-sponsored clinical trial after participating in the first one. It is not known why this may be, but one can assume the first trial came with more “penalties” than “awards” as a reason for the large “drop-out rate”.
We highly recommend a clinical investigator to conduct an in-depth feasibility study before accepting to participate in a trial. We will provide some advice below.
Incentives for Participation in Industry Sponsored Clinical Trials.
It is not easy to point out a single reason or a few good reasons for a physician to participate in an industry-sponsored clinical trial. The incentives for participation are dictated by several factors, such as the type of health care organization, where a doctor is working and his/her area of specialty and experience.
Below, you will find the results of a CTM survey given to clinical trial professionals; 465 individuals responded to the survey.
Author: Johan PE Karlberg. Published in January 2009.
Objective: This study aims to map out the major incentives for investigators to participate in sponsored clinical trials. The study was conducted among Clinical Trial Magnifier subscribers in January 2009.
Response Rate: There were 465 replies. The respondents were from 70 countries: 158 (34.0%) from the US, 98 (21.1%) from Europe excluding former East Europe, and the remaining 209 (44.9%) from other geographic regions.
Table 1. What is your view on the incentives for an INVESTIGATOR TO PARTICIPATE in a sponsored clinical trial? Percentage represents “Fully Agree”. Investigators versus non-site staff.
|Domain||Investigators (%)||Non-site staff (%)||Difference (%)|
|Scientific / Academic merit||48.0||34.6||13.4|
|Institutional / Departmental requirement||9.5||12.5||-3.0|
|Advancement in scientific knowledge||52.0||37.0||15.0|
|Interesting / Not routine work||20.9||15.4||5.5|
|Participation in meetings overseas||4.7||14.4||-9.7|
|Access to potentially new treatments for patients||43.9||42.3||1.6|
|Financial support for investigator's/staff's salary||24.3||32.7||-8.4|
|Financial support for organization's activities||17.6||25.5||-7.9|
|Financial support for other research||23.0||21.2||1.8|
Comments Table 1: Survey responses of clinical investigators and non-investigators (persons not working at a study site). First publications, science and access to new medicines are rated highest, while meeting participation, networking and financial profit are rated lowest. There are clear differences of opinion with regard to the incentives for a clinical investigator to participate in an industry-sponsored clinical trial. For instance, the investigators place more emphasis on science and less on meeting participation, networking and financial benefits.
Table 2. What is your view on the incentives for an INVESTIGATOR TO PARTICIPATE in a sponsored clinical trial? Percentage represents “Fully Agree”. Comparison with US trial professionals and non-US trial professionals.
|Domain||US (%)||Non-US (%)||Difference (%)|
|Scientific / Academic merit||46.8||39.4||7.4|
|Institutional / Departmental requirement||15.2||10.4||4.8|
|Advancement in scientific knowledge||49.4||42.7||6.7|
|Interesting / Not routine work||24.7||16.6||8.1|
|Participation in meetings overseas||7.0||11.4||-4.4|
|Access to potentially new treatments for patients||54.4||40.1||14.3|
|Financial support for investigator's/staff's salary||41.8||25.1||16.7|
|Financial support for organization's activities||29.1||19.5||9.6|
|Financial support for other research||27.8||20.2||7.6|
Comments Table 2: The two geographic groups have a somewhat different view on the incentives for a clinical investigator to participate in an industry-sponsored clinical trial. Respondents from the US place more importance on access to new treatment and salary support for research staff, and less on scientific publications.
Summary findings (Con't)
Table 3. What is your view on the reasons for an INVESTIGATOR TO REJECT PARTICIPATION in a sponsored clinical trial? Percentage represents “Fully Agree”. Investigators versus non-site staff.
Domain Investigators (%) Non-site staff (%) %
Insufficient time 31.1 31.3 -0.2
Limited support staff 36.5 32.7 3.8
Limited space / facilities 20.9 20.2 0.7
Competing trials 16.9 23.6 -6.7
Not enough patients / subjects 22.3 21.6 0.7
In doubt of the product's efficacy 29.7 18.3 11.4
Adverse effect concerns 28.4 20.2 8.2
Difficult protocol 17.6 18.3 -0.7
Low budget 26.4 28.4 -2.0
Poor contract terms 25.7 21.2 4.5
No / Restricted publication right 26.4 14.9 11.5
Other participating investigator(s) 1.4 2.4 -1.0
Administrative bureaucracy of affiliated organization 13.5 13.5 0.0
Bad experiences with sponsor / CRO 15.5 17.8 -2.3
Involvement of CRO / other middleman 6.8 3.8 3.0
Comments Table 3: The comparisons are made between investigators and non-site staff, i.e. the industry. In summary, insufficient time, limited staff support, lack of subjects, potential side effects, and low efficacy are concerns, alongside low budget, poor contract terms and restricted publication rights. The main differences between the two groups are the test product efficacy and publications rights.
Table 4. What is your view on the reasons for an INVESTIGATOR TO REJECT PARTICIPATION in a sponsored clinical trial? Percentage represents “Fully Agree”. Comparison with US trial professionals and non-US trial professionals.
Domain US (%) Non-US (%) Difference (%)
Insufficient time 39.2 29.3 9.9
Limited support staff 43.7 30.9 12.8
Limited space / facilities 25.9 19.2 6.7
Competing trials 29.7 18.2 11.5
Not enough patients / subjects 30.4 20.8 9.6
In doubt of the product's efficacy 22.8 24.8 -2.0
Adverse effect concerns 32.3 23.1 9.2
Difficult protocol 29.1 17.6 11.5
Low budget 49.4 24.1 25.3
Poor contract terms 39.9 19.5 20.4
No / Restricted publication right 17.7 17.9 -0.2
Other participating investigator(s) 2.5 1.6 0.9
Administrative bureaucracy of affiliated organization 13.9 13.4 0.5
Bad experiences with sponsor / CRO 20.3 15.0 5.3
Involvement of CRO / other middleman 5.7 6.5 -0.8
Comments Table 4: Overall, the US representatives have rated insufficient time and limited staff support, competing trials, difficult trial protocol, low budget and poor contractual terms as reasons for non-participation.
Positive versus negative incentives
Note that about 30% of all study sites of the industry-sponsored trials are "zero" sites, i.e. the site has recruited a single trial subject. Another 20-30% of the sites only contribute with a few subjects. These figures have stabilized during the past two decades, and there have not been an improvement over time despite much effort by the industry.
The reason for this poor performance at the site is the utilization of poor feasibility study methods by both the industry and the study sites. The poor subject recruitment at about 50% of the study sites explains why they will only participate in one trial. Poor subject recruitment rate will punish the site financially since payment to the study site is based on the completed number of subject visits. Many times a site employs extra staff for a trial, because the expectation is for the site to recruit the pre-set target number of subjects.
In the following section, we will list out and discuss various issues that discourage trial participation. This is not a comprehensive list, rather just a start so that each investigator can tailor-make his/her own list. The incentives are not listed as positive or negative since different issues—budget or contract—can be rated along one scale, from positive to negative.
Previous experiences with sponsor/CRO: If possible, the site should find information about the performance of the local office of a sponsor/CRO. If information cannot be found, it is likely that the site has no recent experience. However, if the site belongs to a trial network/centre, the site should contact the central administration to discuss the past experiences in collaborating with the sponsor/CRO in question.
Trial feasibility: Each trial protocol is unique and different. In order to fully understand the details of the trial, the study site must review the final study protocol and the Investigator's Brochure. By reading those two trial specific documents, the investigator should be able to understand: if the study is of general interest; if the study comes with any scientific merit; if the study design is optimal and suitable for the research question; if the study would increase the investigator's scientific/clinical knowledge; if the test product has shown to be safe and the side effects that may be expected; if the test product has shown efficacy of clinical importance ; if the study offers access to new, promising treatment for the site's patients; and if the trial includes a placebo group and how this can affect the treatment, recruitment and retention of the subjects. Find out more under: Trial Evaluation
Positive versus negative incentives (cont.)
Subject availability: If the investigator finds the trial protocol and the information provided in the Investigator's Brochure acceptable, the site should find out how many patients the site would be able to recruit for the study. Many protocols have very stringent inclusion and exclusion criteria so it is virtually impossible to make an accurate "guess" of the proportion of the clinic's patient pool that will fulfill the inclusion and exclusion criteria. It is recommend and worthwhile to perform a feasibility study by reviewing 10 or 20 patient records to obtain a better estimate. There are also other factors that influence the recruitment rate and subject retention rate, such as the duration of the trial, placebo treatments, number of site visits and the complexity of the trial. It is also important to discuss the impact of 'competitive recruitment' for sites involved in the same trial. Find out more under Subject Recruitment
Are we ready to take on this trial? When the investigator deems the trial to be suitable and knows that his/her site has enough subjects, there are still other issues to consider, including time requested by the protocol; time available; space availability; support staff availability; competing trials; and administrative support (e.g. ethics committee application, contract and budget negotiation, and payment tracking).
Trial agreement: There are a number of issues in a clinical trial agreement that should be reviewed and negotiated. Find out more under Trial Agreement
Trial budget: There are a number of issues in a clinical trial budget that should be reviewed and negotiated. Find out more underTrial Budget