wienui
★    

Germany/Oman,
2022-07-07 10:37
(38 d 23:00 ago)

Posting: # 23111
Views: 762
 

 Conflicts of interest (COI) & CRO belong to the pharmaceutical Company (CRO b2Ph [Regulatives / Guidelines]

I think addressing this topic is not new for most of you, but what is new is the increasing frequency of discovery of many cases of fraud in the clinical trials & BE in the past few years, starting with GVK (copied ECG), Semler (Subjects samples substituted & diluted) and similarly used methods with Panecexell & Synchron (Samples switch & dilution), by the way, Anders Fuglsang will hold a presentation about the smart techniques he's developed (Buster routines ‘trends’)+ SaToWIB routines ‘Profile similarity’) to detect such type of manipulation on Jordan, on the 4th MENA Conference on the 19th and 20th of September, looking forward to learning more from this genius.

Here, I don’t want to discuss the reasons that led to this, as some of them are clearly known to us, including those related to regulatory bodies (strict Guidelines (GL) + lack of expertise on both sides), by the way, those series of frauds will make the GL more strict, (ICH 10 asked now for 100% chromatograms) which led to the elongated registration process and decrease the profit margin for pharmaceutical companies due to the high cost of those studies and some on the other hand related to the companies, and that brings me to a real story I have heard that the sponsor refused to pay the remaining amount to the CRO because the BE study was failed!!

As we all know, COI could cause biased trial results and create the risk of misconduct (Manipulation) and COI interest arise when clinical investigators have relationships with the company that manufactures the drug that is the subject of the investigation.

Obviously, This COI will of course definitely increase the cases of fraud in clinical trials especially when the CRO belongs to the pharmaceutical company.

Recently, we discussed the matter of accepting BE studies that are performed in CRO belonging to the pharmaceutical companies if this contradicts the principles of COI and therefore the files of these studies should not be received or accepted.

Unfortunately, there is nothing clear in any Guidelines that regulates (allowing or denying) this matter, therefore the opinions of colleagues are very important in setting the right direction.

Cheers,
Osama
Ohlbe
★★★

France,
2022-07-07 10:55
(38 d 22:42 ago)

@ wienui
Posting: # 23112
Views: 653
 

 Conflicts of interest (COI) & CRO belong to the pharmaceutical Com­pany (CRO b2Ph

Dear Osama,

» what is new is the increasing frequency of discovery of many cases of fraud in the clinical trials & BE in the past few years, starting with GVK [...]

Before that you had the generic drug scandal in the US in the '80s, the WHO removing multiple products from Cipla, Ranbaxy and Hetero from the prequalification list in 2004, Cetero in the US... What may be new is that you now hear of such cases (much more media buzz, and amplification by social media) and the "if we ever catch you, we'll just reject everything you ever did" attitude from regulators, trying to have a deterrent effect.

» [...] that brings me to a real story I have heard that the sponsor refused to pay the remaining amount to the CRO because the BE study was failed!!

Yes, there are a number of things that the Man in the Armani suit would need to be explained, if one of his underlings dares to speak. Such attitude is pushing for fraud.

» Recently, we discussed the matter of accepting BE studies that are performed in CRO belonging to the pharmaceutical companies if this contradicts the principles of COI and therefore the files of these studies should not be received or accepted.

Yes, in such situations you indeed have a higher risk of internal pressure, pushing to do stupid things. But this is not limited to BE, and you have the same problem with pharmaceutical development, finished product stability studies and so on. Look at what happened at Ranbaxy in the past. Did you read Katherine Eban's "Bottle of lies" ?

Regards
Ohlbe
dshah
★    

India/United Kingdom,
2022-07-07 18:52
(38 d 14:44 ago)

@ Ohlbe
Posting: # 23113
Views: 580
 

 Conflicts of interest (COI) & CRO belong to the pharmaceutical Company (CRO b2Ph

Dear All!
I believe that there are a lot other issues which require further highlight. Recently there were questions with respect to vaccine trial and efficacy. The Unlimited Medical Research at Florida were found to be guilty for Obstructing FDA Inspection.
Even blood pressure range were reduced in recent time which ultimately results in higher sales of antihypertensive drugs.
Regards,
Divyen
wienui
★    

Germany/Oman,
2022-07-07 20:48
(38 d 12:49 ago)

@ dshah
Posting: # 23114
Views: 577
 

 Conflicts of interest (COI) & CRO belong to the pharmaceutical Company (CRO b2Ph

Dear Ohlbe ,Divyen & all,

Yes, the pot is full and this calls us (Regulatory + Industry) to unite to fight those types of frauds, otherwise, the patient will lose complete confidence in the drugs, especially the Generic drugs.
But let us return to the main topic, should the regulatory authorities refuse the submission and acceptance of BE studies that have been performed in a CRO belonging to the sponsor? are there any references? or are there other opinions other than that?

Cheers,
Osama
dshah
★    

India/United Kingdom,
2022-07-08 10:23
(37 d 23:13 ago)

@ wienui
Posting: # 23115
Views: 526
 

 Conflicts of interest (COI) & CRO belong to the pharmaceutical Company (CRO b2Ph

Dear Osama!
» But let us return to the main topic, should the regulatory authorities refuse the submission and acceptance of BE studies that have been performed in a CRO belonging to the sponsor? are there any references? or are there other opinions other than that?
Unless study trend/result is too much doubtful, regulatory bodies generally does not refuse for submission and acceptance. I believe as a sponsor, the submission of all the studies including failed one is important during such time as it gives impression that sponsor has appropriate formulation which are BE to RLD.

Regards,
Divyen
ElMaestro
★★★

Denmark,
2022-07-08 13:18
(37 d 20:18 ago)

@ wienui
Posting: # 23116
Views: 504
 

 Conflicts of interest (COI)

Hi wienui and all,

I think this is an excellent topic.
This is not so much discussion of what the current rules are but more about considerations that could make the rules better.

Clearly, one can speculate that a corporate link between sponsor and CRO could somehow bias the result.
I am not saying it does, but I certainly agree it could. That would depend on the details, and these details are completely in the dark in the sense that some of them could be matters that are outside the scope of any type of regulatory scrutiny incl. inspections.

In a wider sense, perhaps this isn't just about CRO vs Sponsor. In my ideal world the Sponsor would not pick the clinical site/CRO or bioanalytical site/CRO; these choices would be at the discretion of some independent party. In my ideal world, the Sponsor would not be trusted to appoint monitor but the need for and extent of monitoring would be dictated by an outside unbiased entity. In my ideal world, the name of the Sponsor would be blind to the assessor after the dossier were submitted. I am saying this for a reason. And so forth.

The theoretical feasibility for such ideas is low or nil, though. Perhaps because my ideas of the ideal world are not shared by anyone else but also be because the system just moves very slowly. A member of the forum mentioned how ideas aired at Crystal City in 2006 materialised only in 2022. Go figure... That's 16 years.
So, a lot of the discussion related to regulatory science is not just science. It is science given a system which happens to be somewhat inert.

Pass or fail!
ElMaestro
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2022-07-08 16:29
(37 d 17:07 ago)

@ ElMaestro
Posting: # 23117
Views: 499
 

 Off topic

Hi ElMastro,

» A member of the forum mentioned how ideas aired at Crystal City in 2006 materialised only in 2022. Go figure... That's 16 years.

Not that bad. Though I can top that.
Reference-scaling for HVD(P)s was first proposed at the BioInternational ’89 in Toronto. Appeared in guidelines in 2010. You can do the math.

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ElMaestro
★★★

Denmark,
2022-07-08 16:54
(37 d 16:42 ago)

@ Helmut
Posting: # 23118
Views: 495
 

 Off topic

» Reference-scaling for HVD(P)s was first proposed at the BioInternational ’89 in Toronto. Appeared in guidelines in 2010. You can do the math.

Easy maffs.
2010-89 is 1921. Astonishingly slow, innit?:-D

Pass or fail!
ElMaestro
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2022-07-08 20:41
(37 d 12:55 ago)

@ ElMaestro
Posting: # 23119
Views: 474
 

 Off topic

Hi ElMaestro,

» » Reference-scaling for HVD(P)s was first proposed at the BioInternational ’89 in Toronto. Appeared in guidelines in 2010. You can do the math.
»
» Easy maffs.
» 2010-89 is 1921. Astonishingly slow, innit?:-D

[image]You missed the apostrophe. BioInternational ’89 was the official name of the conference when the Y2K bugwas in the future. Agilent rolled out a patch for it’s LIMS (HP LAB/UX) in mid-No­vem­ber (!) 1999. I was in the lab and made an injection a couple of minutes after midnight to check. ;-)

I will be almost 80 when the Epochalypsemay hit old code.

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wienui
★    

Germany/Oman,
2022-07-08 22:18
(37 d 11:18 ago)

@ Helmut
Posting: # 23120
Views: 468
 

 CRO belong to the pharmaceutical Company (CRO b2Ph

Hi Captian ElMaestro, Helmut & all,

Should I understand that you think these kinds of studies "performed in CRO belong to the pharmaceutical Company" should be blocked and not accepted due to the high risk of COI and the possibility of manipulating the studies' outcomes.
Is there any guidance, or literature on which we can rely on it to regulate this issue?
Please kindly express your opinion clearly and frankly, it will help a lot.

Cheers,
Osama
ElMaestro
★★★

Denmark,
2022-07-09 08:51
(37 d 00:46 ago)

@ wienui
Posting: # 23121
Views: 438
 

 CRO belong to the pharmaceutical Company (CRO b2Ph

Hi wienui,

» Should I understand that you think these kinds of studies "performed in CRO belong to the pharmaceutical Company" should be blocked and not accepted due to the high risk of COI and the possibility of manipulating the studies' outcomes.
» Is there any guidance, or literature on which we can rely on it to regulate this issue?
» Please kindly express your opinion clearly and frankly, it will help a lot.


I think I see your point, but I think it is asking too much in practice. Claiming that an existing relationship between Sponsor and CRO implies a high risk is a postulate, but I must emphasize that I agree to some extent. There is just no good alternative, is there? It may be impractical if we require that CROs can't be owned by the Sponsor.
a. I do not know of any guidance that really helps directly here but there are plenty clauses in ICH E6r2 that could be used on interpretation. If you think a COI exists and it will bias the outcome, then something like §2.5 or §2.13 might come in handy.
b. We need to bear in mind that many originators still have clinical departments that act as the company's own CRO (the only real difference being it may be called a division rather than a CRO). Would we also enforce a COI concern over those clinical departments? Why? Why not?
c. Defining what a "relation" is, and what is means to be "owned" etc is a legal mess. This is the playground of lawyers. I am sure that if we were to make an amendment in a guideline to the effect of "CROs cannot be owned by Sponsors" or whatever wording we use then I am sure it would change very little as CROs in question would just change the corporate setup to escape the issue.

Pass or fail!
ElMaestro
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2022-07-09 19:21
(36 d 14:15 ago)

@ ElMaestro
Posting: # 23122
Views: 420
 

 CRO subsidiary of pharmaceutical company

Hi ElMaestro & Osama,

» b. We need to bear in mind that many originators still have clinical departments that act as the company's own CRO (the only real difference being it may be called a division rather than a CRO). Would we also enforce a COI concern over those clinical departments? Why? Why not?
» c. Defining what a "relation" is, and what is means to be "owned" etc is a legal mess. This is the playground of lawyers. I am sure that if we were to make an amendment in a guideline to the effect of "CROs cannot be owned by Sponsors" or whatever wording we use then I am sure it would change very little as CROs in question would just change the corporate setup to escape the issue.

For almost four years I was in a similar situation. The CRO (performing all the good stuff except the clinical part) was an ‘independent’ company though 100% owned by a generic company. Did we care whether a study passed or failed? Of course, not. A failed study is great cause you will get another one. ;-)
My boss (incidentally the nephew of the big boss) tried to convince him to work also for other companies. No way. In 1984 we founded our own CRO. My boss was disinherited. Didn’t regret it.

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