Question asked on Linked in GCP group:Hi! For one of my studies, three months after the start of the recruitment, I discover the site has a competing protocol (same inclusion/exclusion criteria). What do you do in my place?
The question was commented as follows:
Stefania Bordin • I would suggest to check the Investigator availability in terms of time an recruitment potentials. Anyway, in order to avoid such risks during the fesibility phase and site choice the Investigator shoul have completed a questionnaire by indicating if he/ she has competitors' studies ongoing. In any case by signing the Protocol page he / she committs himself to conduct the trial according to Protocol which also includes all the time required to conduct the trial in the correct whay (beyond, for sure according to GCP ICH and all the regulations being applicable in this case). At the end, if you notice that the enrolment for your tiral is not good enough not even in terms of screening you can inform your head department and project manager in order to agree about the possibility to close the site.
Fatima EL GHAIB • Thanks Stefania.
During the feasibility phase, the Investigator completed the questionnaire indicating he has no competiting studies ongoing.
Just for information, how is it possible to use such a document legally?
Rebecca Georgevitch • He was already fabricating the truth prior to study acceptance. I don't believe this was a legal issue. At this point, I would be very cautious with this site and any Information given to me. He lied before he even began the trial. If they were open to enrollment and haven't enrolled in sometime, the sponsor/CRO may consider sending him a letter stating they will be shutting down sites that have less than x# of qualified subjects enrolled by a specific time. Try to close them down before the next IRB meeting/approval. This is costing them unnecessary money. I would also discuss future enrollment procedures with the PI and SC present.
Fatima EL GHAIB • Many thanks Rebecca :)
Shirley Isbill • There may be no need to do anything. It's not uncommon for study sites to run mulitple studies for several sponsors. The last study site I audited, had 30 active studies and they were recruiting for more. You can make an assessment of the study site staffing and comment to your study sponsor concerning the staff's ability to handle their clinical study workload. It would not be ethical for you to look at the details of the competing study; it might be a competitor's study of their drug for the same indication in your study.
Malaika Simmons • I agree with Shirley. Additionally, if there was a feasibility questionnaire completed that indicated that there were no competing studies, it may be a matter of opinion. For example, your study may be a fibroid study, and the site may have an ongoing endometriosis study. The PI may say that those are two different illnesses, therefore are noncompeting. However, we know that the inc/excl criteria will have similar if not nearly identical parameters.
That being said, you will still have to treat the site as you should all sites, and remind the PI /coordinator of the sites responsibility to recruit to the protocol specifications. It is a good idea to develop a recruitment plan (that includes methods as well as numbers) per site as part of the study initiation as a rule to mitigate under enrollment issues and reemphasizes roles and responsibilities (amazing that signing the 1572 does not immediately impart an overwhelming sense of responsibility! :-)).
Good luck
Fatima EL GHAIB • Many thanks to all of you! Your advices are very helpfull :)
In fact, when discussing with another site staff, it appears that they refused another study because very similar: same inclusion/exclusion criteria and same indication! It also appears that these 2 trials were both conducted by the same CRO (I was working for), that's why I had the possibility to read the competitive protocol.
The first site I was speaking about had been less realistic than the second one and accepted to conduct both studies, but finally wasn't able to reach his goal...
Kamakshi Sriram • Hi Fatima,
This is strange as while we are debating on the intentions of site one which has accepted to do competing studies at the same time, I have doubts on the intentions of the CRO now, who is going ahead and enrolling the same investigator for a competing study, the investigator would take the study up if CRO ( representing sponsor here as responsibilities are being delegated) is going ahead and even proposing a new study to the same site. The reason could be either the site is too talented..........or the recruitment period is over of the first study.............or sheer negligence on the part of the CRO.
Christoph Lohan (PgDip.) • Without having more details about the issue I would agree with Malaika. It may just be that the protocols are very similar but not wholly identical as they may target slightly different groups or conditions. In Oncology and Heamatology you will find it alot, e.g. breast cancer or AML. Woth looking at it in more detail.
Harpreet Kaur Anand • If Protocol is same, all Inclusion-Exclusion Criteria,Study Duration etc therefore its futile taking such studies.Its merely shows that the site is not interested in study, only concerned with the money they will receive from the it.
1) Patient recruitment will be less as site will be manage to enroll patient in both studies
2) This will be biased
If company is doing research on some molecule they must have targeted patients pool & site accordingly therefore if they will not get the sufficient data from sufficient number of patients then its useless conducting trial at such type of sites in near futute.
Rather than taking any strict action, the site should be warned about this & as per Miss Simmons PI should be reminded/educated of the sites responsibility to recruit to the protocol specifications.
Shirley Isbill • Fatima,
Re: It also appears that these 2 trials were both conducted by the same CRO (I was working for)
It's not uncommon for the left hand to not know what the right hand is doing; refer the common protocols to the CRO then forget about it.
Fatima EL GHAIB • I started in that CRO and on that study after the sites had been selected.
Kamakshi, I agree with you. As CRA I had to be informed by the CRO about the conduct of that competitive study so as to be more vigilant.
Thank you all for your active participation. Your comments are very constructive :)
20 days ago • Unlike • Like • Reply privately• Flag as inappropriate • Flag as promotion0 . Lynda Cedar • It's common for a site to conduct similar studies (study design, same drug or simlar products), the same inc/exc criteria used.
- If a NDA is in place, the site is not supposed to disclose any information about its current studies, other than speaking about their experience with a specific disease or class of medication.
If a NDA is in place, allowing you to know about the other study, and even showing you the study protocol of the other sposnor, that is a violation of the NDA and confidential information provided to the site.
This disclosure is not ethical and might disavantage the other sponsor:if he does not know the same..
- Regarding the recruitment, no worries if a CTRA is in place and contains milestones for the recruitment, the site is going to deliver.
Maneesh Misra • You should consider Kamakshi, Rebecca & Malaika's comments seriously. The trial is not meant for only the Sponsors' drug & Study Design but also for effecasy & safety of patients. To fulfill the needs of NDA(Non Disclosure Agreements), you cannot compromise on the results of the trial which are more likely to be BIASED in this senarion mentioned by you.
It should be your moral responsibility to conduct the trial without any element of BIASED approach or ignorance as seen in this case. The PI may have taken the approach to enable the site to build more credibility & increase the list of achivements but as a professional we should take these issues seriously & act accordingly.
I am not in the correct position to advice you for the approach to be taken to resolve the violations, if any, as the details discussed is not sufficient for it. Ask your self & evaluate it agailst the GCP & IRB guidelines without any Biased thoughts & I am sure you will get the answer yourself.
All the participants made good approach & it is appreciable that these discussions will always help in learning more n more. I have also learned things from this discussion & everyones views & would like to Thank everybody.
Shannen Douglass • It is not uncommon for a site to have competing studies. As long as recruitment targets are being met, protocol is being followed and there is enough time for the staff to properly run both trials, you may not need to do anything at all.
Melvin paul • Hi Fatima,
Most often investigators do not disclose complete information as they feel additional project would help their profile. However in a situation like this it is good to speak to the investigator about your concern and let her/him know that there is an equal commitment that the PI should show to both the studies. You could suggest that he follows a fifty/fifty rule, where if he has two subjects screened on a day, then he should enroll one for one study and the other into the other study. If he could do this then he will ensure he has lived up to the commitments of both the studies. I quote this from a similar experience when i was a CRA. This startergy did work. However you will need to keep and eye on the recruitment time. If you see that the PI is not making any progress, it is better to either close the site or get permission to extend the recruitment time period.
Nancy Nahmias • Many times the site staff completes the feasibility, and the PI just signs it. It is up to the sponsor to do due diligence and review the feasibility and ask questions. Typically sponsors know what protocols are competing with theirs, and as a CRA I always ask this of the project lead.
Since the study has already started, I would put the PI's feet to the fire by ensuring you get regular enrollment logs, and having a lengthy discussion with the PI about enrollment at each visit. I would also mention that this competing protocol was not mentioned on the feasibility, but since they are participating ask the PI how he assigns subjects to a specific trial. If you get a lousy response to enrollment, I would tell the PI that you will close them if they have no enrollment after 3 months....
Bhugol Chandel, MD • Hi Fatima,
As long as the site and the investigator have time, patient population and the resources to enroll the patients, they need to be supported for their efforts to meet enrollment challenge.
Laura C. Collada Ali • What about the Ethics Committee? Is it possible that they do not point out such a case? Don't they have a register of ongoing studies?
Megan Mather • It is to be expected, especially when the PI is in a specialty, such as cardiac research, specific oncology, or neurology. Many moons ago I was a study coordinator working on migraines. I had as many as 7 studies all on migraines. As long as the site can provide a sufficient number of subjects and definite proof that appropriate washouts of drugs from trials are performed, there really shouldn't be a problem. The PI and coordinator should be interviewed on how they keep the trials separate and how they make sure they do not confuse the trials. All study documentation should be kept separate and away from other studies (no shared labs, etc.) and when information is addressed in a common patient file, if these are the PI's private patients as well, only the trial number should be listed in the patient chart. The one area I have special concerns over is during Phase I studies where they have "professional patients". We had to report a site in Florida where there were 2 Phase I units within one mile from the other and we found the patients were going from one unit to the other without washout and in some cases at the same time. Many of the studies were at risk, it was bad news!!
Stefania Bordin • I would suggest to check the Investigator availability in terms of time an recruitment potentials. Anyway, in order to avoid such risks during the fesibility phase and site choice the Investigator shoul have completed a questionnaire by indicating if he/ she has competitors' studies ongoing. In any case by signing the Protocol page he / she committs himself to conduct the trial according to Protocol which also includes all the time required to conduct the trial in the correct whay (beyond, for sure according to GCP ICH and all the regulations being applicable in this case). At the end, if you notice that the enrolment for your tiral is not good enough not even in terms of screening you can inform your head department and project manager in order to agree about the possibility to close the site.
Fatima EL GHAIB • Thanks Stefania.
During the feasibility phase, the Investigator completed the questionnaire indicating he has no competiting studies ongoing.
Just for information, how is it possible to use such a document legally?
Rebecca Georgevitch • He was already fabricating the truth prior to study acceptance. I don't believe this was a legal issue. At this point, I would be very cautious with this site and any Information given to me. He lied before he even began the trial. If they were open to enrollment and haven't enrolled in sometime, the sponsor/CRO may consider sending him a letter stating they will be shutting down sites that have less than x# of qualified subjects enrolled by a specific time. Try to close them down before the next IRB meeting/approval. This is costing them unnecessary money. I would also discuss future enrollment procedures with the PI and SC present.
Fatima EL GHAIB • Many thanks Rebecca :)
Shirley Isbill • There may be no need to do anything. It's not uncommon for study sites to run mulitple studies for several sponsors. The last study site I audited, had 30 active studies and they were recruiting for more. You can make an assessment of the study site staffing and comment to your study sponsor concerning the staff's ability to handle their clinical study workload. It would not be ethical for you to look at the details of the competing study; it might be a competitor's study of their drug for the same indication in your study.
Malaika Simmons • I agree with Shirley. Additionally, if there was a feasibility questionnaire completed that indicated that there were no competing studies, it may be a matter of opinion. For example, your study may be a fibroid study, and the site may have an ongoing endometriosis study. The PI may say that those are two different illnesses, therefore are noncompeting. However, we know that the inc/excl criteria will have similar if not nearly identical parameters.
That being said, you will still have to treat the site as you should all sites, and remind the PI /coordinator of the sites responsibility to recruit to the protocol specifications. It is a good idea to develop a recruitment plan (that includes methods as well as numbers) per site as part of the study initiation as a rule to mitigate under enrollment issues and reemphasizes roles and responsibilities (amazing that signing the 1572 does not immediately impart an overwhelming sense of responsibility! :-)).
Fatima EL GHAIB • Many thanks to all of you! Your advices are very helpfull :)
In fact, when discussing with another site staff, it appears that they refused another study because very similar: same inclusion/exclusion criteria and same indication! It also appears that these 2 trials were both conducted by the same CRO (I was working for), that's why I had the possibility to read the competitive protocol.
The first site I was speaking about had been less realistic than the second one and accepted to conduct both studies, but finally wasn't able to reach his goal...
Kamakshi Sriram • Hi Fatima,
This is strange as while we are debating on the intentions of site one which has accepted to do competing studies at the same time, I have doubts on the intentions of the CRO now, who is going ahead and enrolling the same investigator for a competing study, the investigator would take the study up if CRO ( representing sponsor here as responsibilities are being delegated) is going ahead and even proposing a new study to the same site. The reason could be either the site is too talented..........or the recruitment period is over of the first study.............or sheer negligence on the part of the CRO.
Christoph Lohan (PgDip.) • Without having more details about the issue I would agree with Malaika. It may just be that the protocols are very similar but not wholly identical as they may target slightly different groups or conditions. In Oncology and Heamatology you will find it alot, e.g. breast cancer or AML. Woth looking at it in more detail.
Harpreet Kaur Anand • If Protocol is same, all Inclusion-Exclusion Criteria,Study Duration etc therefore its futile taking such studies.Its merely shows that the site is not interested in study, only concerned with the money they will receive from the it.
1) Patient recruitment will be less as site will be manage to enroll patient in both studies
2) This will be biased
If company is doing research on some molecule they must have targeted patients pool & site accordingly therefore if they will not get the sufficient data from sufficient number of patients then its useless conducting trial at such type of sites in near futute.
Rather than taking any strict action, the site should be warned about this & as per Miss Simmons PI should be reminded/educated of the sites responsibility to recruit to the protocol specifications.
Shirley Isbill • Fatima,
Re: It also appears that these 2 trials were both conducted by the same CRO (I was working for)
It's not uncommon for the left hand to not know what the right hand is doing; refer the common protocols to the CRO then forget about it.
Fatima EL GHAIB • I started in that CRO and on that study after the sites had been selected.
Kamakshi, I agree with you. As CRA I had to be informed by the CRO about the conduct of that competitive study so as to be more vigilant.
Thank you all for your active participation. Your comments are very constructive :)
Lynda Cedar • It's common for a site to conduct similar studies (study design, same drug or simlar products), the same inc/exc criteria used.
- If a NDA is in place, the site is not supposed to disclose any information about its current studies, other than speaking about their experience with a specific disease or class of medication.
If a NDA is in place, allowing you to know about the other study, and even showing you the study protocol of the other sposnor, that is a violation of the NDA and confidential information provided to the site.
This disclosure is not ethical and might disavantage the other sponsor:if he does not know the same..
- Regarding the recruitment, no worries if a CTRA is in place and contains milestones for the recruitment, the site is going to deliver.
Maneesh Misra • You should consider Kamakshi, Rebecca & Malaika's comments seriously. The trial is not meant for only the Sponsors' drug & Study Design but also for effecasy & safety of patients. To fulfill the needs of NDA(Non Disclosure Agreements), you cannot compromise on the results of the trial which are more likely to be BIASED in this senarion mentioned by you.
It should be your moral responsibility to conduct the trial without any element of BIASED approach or ignorance as seen in this case. The PI may have taken the approach to enable the site to build more credibility & increase the list of achivements but as a professional we should take these issues seriously & act accordingly.
I am not in the correct position to advice you for the approach to be taken to resolve the violations, if any, as the details discussed is not sufficient for it. Ask your self & evaluate it agailst the GCP & IRB guidelines without any Biased thoughts & I am sure you will get the answer yourself.
All the participants made good approach & it is appreciable that these discussions will always help in learning more n more. I have also learned things from this discussion & everyones views & would like to Thank everybody.
Shannen Douglass • It is not uncommon for a site to have competing studies. As long as recruitment targets are being met, protocol is being followed and there is enough time for the staff to properly run both trials, you may not need to do anything at all.
Melvin paul • Hi Fatima,
Most often investigators do not disclose complete information as they feel additional project would help their profile. However in a situation like this it is good to speak to the investigator about your concern and let her/him know that there is an equal commitment that the PI should show to both the studies. You could suggest that he follows a fifty/fifty rule, where if he has two subjects screened on a day, then he should enroll one for one study and the other into the other study. If he could do this then he will ensure he has lived up to the commitments of both the studies. I quote this from a similar experience when i was a CRA. This startergy did work. However you will need to keep and eye on the recruitment time. If you see that the PI is not making any progress, it is better to either close the site or get permission to extend the recruitment time period.
Nancy Nahmias • Many times the site staff completes the feasibility, and the PI just signs it. It is up to the sponsor to do due diligence and review the feasibility and ask questions. Typically sponsors know what protocols are competing with theirs, and as a CRA I always ask this of the project lead.
Since the study has already started, I would put the PI's feet to the fire by ensuring you get regular enrollment logs, and having a lengthy discussion with the PI about enrollment at each visit. I would also mention that this competing protocol was not mentioned on the feasibility, but since they are participating ask the PI how he assigns subjects to a specific trial. If you get a lousy response to enrollment, I would tell the PI that you will close them if they have no enrollment after 3 months....
Bhugol Chandel, MD • Hi Fatima,
As long as the site and the investigator have time, patient population and the resources to enroll the patients, they need to be supported for their efforts to meet enrollment challenge.
Laura C. Collada Ali • What about the Ethics Committee? Is it possible that they do not point out such a case? Don't they have a register of ongoing studies?
Megan Mather • It is to be expected, especially when the PI is in a specialty, such as cardiac research, specific oncology, or neurology. Many moons ago I was a study coordinator working on migraines. I had as many as 7 studies all on migraines. As long as the site can provide a sufficient number of subjects and definite proof that appropriate washouts of drugs from trials are performed, there really shouldn't be a problem. The PI and coordinator should be interviewed on how they keep the trials separate and how they make sure they do not confuse the trials. All study documentation should be kept separate and away from other studies (no shared labs, etc.) and when information is addressed in a common patient file, if these are the PI's private patients as well, only the trial number should be listed in the patient chart. The one area I have special concerns over is during Phase I studies where they have "professional patients". We had to report a site in Florida where there were 2 Phase I units within one mile from the other and we found the patients were going from one unit to the other without washout and in some cases at the same time. Many of the studies were at risk, it was bad news!!
Tom Quegan • Very interesting discussion!
Fatima, there is another point that has not yet been discussed. Did/does the PI know that he has two competing studies? Does he have full oversight of all his studies, or does he delegate everything to study coordinators and sub-investigators?
As an auditor, I have been to sites where the PI could not tell me about critical parts of the protocol, so this may be something that you want to be aware of.
13 days ago • Unlike • Like • Reply privately• Flag as inappropriate • Flag as promotion3 .
Molly Blake-Michaels • Hello Fatima,
The only comment I have to add to the discussion is that in cases where there are studies that compete for the same patients, it is always advisable to find out how the site will decide which patient will be enrolled into each study. For example, I have worked with sites in the past that have alternated studies; as eligible patients come in they are offered the study whose "turn" it is. If a procedure like that isn't in place, it is easy for an investigator's bias to result in different types of patients being enrolled in one study than the other (for example, if the investigator believes that heavier patients will do better on the drug in Study X, or older patients will do worse, it could easily affect their decision as to which study to present to the patient). The result of this bias can be that the full range of patients meeting the inclusion/exclusion criteria are not enrolled, at least at that site.
Anke Hoppe • If this constitutes a protocol violation, the chain of events starting with discovery of the issue and actions taken (e.g. re-training of PI, set up of recruitment plan, ensuring maintenance of confidentiality for each study etc.) need to be documented detailed in writing, signed and filed accordingly (ISF and TMF) and the site needs to inform their IRB.
Does the CTA address this kind of incidence?
Anupama Ramkumar • The objective of anyone who is assessing these sites(monitor,auditor etc) is to ensure that the data is credible and that the patients safety and well being is not compromised.
It is not uncommon for sites to be handling multiple trials at the same time and not only that but also be a highest recruiter!!
At all times if all the stakeholders can keep the objectives of data credibility and patient safety in mind ,there really are no restrictions.
Which means there has to be an audit trail which should include documentation to ensure that the inclusion/exclusion criteria are not being compromised and that the patient is not part of more than one trial.
Dennis McHugh • If inclusion/exclusion criteria and protocols are substantially equivalent suggest that they enroll in one trial on even days; the other on odd days or alternate weeks. This would be treating both programs equally and perhaps avoid bias. You do want to avoid investigator bias where they believe (consciously or unconsciously) that Study A might just have the superior intervention so they enroll the more challenging subjects there. That's an experimental model killer.
Patrick Martin • Fatima it appears that you are very conscientious and diligent in managing the site, which is great. Regarding your post: as I used to tell my team, when in doubt, ask.
There's nothing wrong in bringing those concerns to the PI in a professional and respectful manner. At the very least the site will know that you want open and honest communication. But the bottom line is do you honestly think that the site/PI has the ability to meet the obligations, including timely enrollment, for your study? If the answer is yes, then go forward. If no, then talk to your boss.
For what it's worth, if the site has expertise in a particular area then one would expect that other sponsors would be attracted to work w/ the site as well. If the site is large enough they may have the patient load to adequately enroll in your study and the other.
Best of luck with this.
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