Subject: Re: TB REACH V7 Application for your review and comments
From: Vivian Cox <[email-masked]>
To: Tamar Gabunia <[email-masked]>
Cc: Nestan Tukvadze <[email-masked]>, Nelly Solomonia <[email-masked]>, Nino Lomtadze <[email-masked]>, Maka Danelia <[email-masked]>, Irma Khonelidze <[email-masked]>, Mari Buziashvili <[email-masked]>, Zaza Avaliani <[email-masked]>, Natalia Adamashvili <[email-masked]>, "[email-masked]" <[email-masked]>
Date: Sun, 01 Sep 2019 13:15:30 +0000

Dear Nestani and all,
The grant application reads very well - no further comments from my side.  Best of luck with the submission, and I hope the proposal is successful.  Kind regards, Vivian

On Sep 1, 2019, at 2:54 PM, Tamar Gabunia <[email-masked]> wrote:

Good luck with this submission!

Many thanks to all who have contributed to this great work.

Best

Tamar

From: Nestan Tukvadze [mailto:[email-masked]]

Sent: 1 September, 2019 16:52

To: Nelly Solomonia <[email-masked]>; Vivian Cox <[email-masked]>; Nino Lomtadze <[email-masked]>; Tamar Gabunia <[email-masked]>; Maka Danelia <[email-masked]>; Irma Khonelidze <[email-masked]>; Mari Buziashvili <[email-masked]>;
Zaza Avaliani <[email-masked]>; Natalia Adamashvili <[email-masked]>; Nana Kiria <[email-masked]>

Subject: Re: TB REACH V7 Application for your review and comments

Dear Colleagues,

As we have not received any additional comments we will finalize files and Mariana Buziashvili will submit it via email (as was instructed) within next hour.

Thank you once again for the team work and contributions and let us hope that application will be successful.

With best,

Nestani

Nestani Tukvadze Head of Research Unit National Center for Tuberculosis and Lung Diseases 50 Maruashvili str. 0101 Tbilisi, Georgia. Tel: (995 32) 2910769 Cell: (995) 593733334

On Saturday, August 31, 2019, 9:00:54 PM GMT+4, Nelly Solomonia <[email-masked]> wrote:

Dear Colleagues,

Thank you very much for your excellent work.

Please, attached find final 2 comments on pages 7 and 9.

Sincerely,

Nelly

On Sat, 31 Aug 2019 at 14:19, Nestan Tukvadze <[email-masked]> wrote:

Dear Colleagues,

With attachment sharing the final drafts of: proposal, work-plan, detailed budget and indicators.

Will wait for your feedback till tomorrow, Sunday 1pm. After making final edits based on your inputs we will submit it to Stop-TB.

We will work on the grammar and formatting after your inputs tomorrow.

Thank you!!!

Nestani, Mariana, Natalia

Nestani Tukvadze Head of Research Unit National Center for Tuberculosis and Lung Diseases 50 Maruashvili str. 0101 Tbilisi, Georgia. Tel: (995 32) 2910769 Cell: (995) 593733334

On Thursday, August 29, 2019, 5:24:06 PM GMT+4, Nino Lomtadze <[email-masked]> wrote:

Dear Nestani and dear colleagues,

Please find the version from me that I revised after Tamar and Vivian's comments, but not the final version sent by Vivian few minutes ago.  Have added some
data in absolute numbers and interventions specific for PK capacity building. I think this is a good idea to include that component in the proposal. You will see my few comments throughout the document as well.

Thank you!

Nino

Nino Lomtadze, MD., MSc

Head of Surveillance and Strategic Planning Department

Coordinator of the Global Fund TB Program (GEO-T-NCDC) in Georgia

JSC "National Center for Tuberculosis and Lung Diseases"

8, Achara str.

Tbilisi, 0101

Georgia

Phone (work): (+995 32) 2911116 (Ext.123)

Phone (cell): (+995 599) 88 81 71

Multidrug-Resistant TB Clinical Consultant,

UNOPS/Stop TB Partnership International ICA

GLC Consultant, WHO Euro, EU/CDS - Communicable Diseases

On Thu, Aug 29, 2019 at 3:06 PM Vivian Cox <[email-masked]> wrote:

Dear Nestani,

Thank you for sharing the feedback from TB Alliance on the grant proposal.  I am not sure about adjusting the proposal to a pragmatic clinical trial, since
as you say the timeline of TB REACH is so short.  Instead, I adjusted the language in the draft (please see attached as “VC2” and use this draft for my inputs) and used the terms “programmatic implementation of BPaL under closely monitored operational research
conditions.” This mostly implies that the regimen will be introduced programmatically but with very careful clinical monitoring and collection of high quality data for analysis and sharing with others (like WHO) for things like meta-analyses.  This is the
terminology that WHO has used to allow for introduction of modified fully oral shorter regimens (like the mSTR you’re implementing in Georgia).  And I would think that other proposals, say for instance the KNCV proposal for some of their countries to implement
BPaL, has also been worded around operational research.  TB Alliance has the point that without WHO guidance on BPaL yet, it might be difficult for Stop TB Partnership/TB REACH to approve proposals that use it in this way.  That being said, the WHO Guideline
Development Group is meeting in November, and they are supposed to review the Nix data and FDA approval, so we could also add a sentence or two to say this - that in addition to doing this project under OR conditions, we will likely have some further guidance
from WHO by the time this project would be starting.

I’ve added in some language to this draft on some of the cost drivers - they mostly agree with yours listed below.  See the executive summary for my suggestions.

I am happy to have a short call on the enrollment target of 100, as well as the treatment outcomes only at the end of treatment given the tight timeline - as
well as any other points you’d like to discuss.  I am free anytime tomorrow morning until 11:00 Cape Town time, if that works for others?  Thanks, Vivian

On Aug 29, 2019, at 2:21 PM, Nestan Tukvadze <[email-masked]> wrote:

Dear Colleagues,

Many thanks to everyone for very quick and valuable feedback!

We will start incorporation/editing of proposal and also drafting other components of application.

Also hope we will have GF cost-sharing component on time, as have not heard back so far.

I also got general feedback from TB Alliance, that they can not be partners due to COI and as for the proposal they think it will be a bit difficult to get
funding for programmatic implementation.

There is still time to adjust proposal on PCT (pragmatic clinical trial), but not sure whether this is a good idea and I believe initial suggestion was to focus
on Programmatic implementation, please let me know if this is not the case? Other problem with PCT is timeline which obviously is too short for such study.

As for the main cost drivers I agree with both Tamar and Vivian, for programmatic implementation we do not have much to request but:

- Pretomanid cost (which was negotiated by Mylan) and will be provided with the same cost as Bedaquiline.

- Some for capacity building of clinicians and lab staff (will adjust this components in the main text)

- Costs for Pharmacokinetics (importent to have Nino's feedback on this)

- Some amount on project personal costs (15%)

If you have
any other suggestions will be great to know before we work on the budget narrative.

Important points regarding proposal:

- Control group:

when we claim 100 patients on BPaL it is not realistic within six month enrollment period, but this numbers came form Stop-TB so we are leaving as it is, therefore
for sure at the same time period we will not have any patients left to use as controls. That was a reason to indicate historical cohort which I agree is not ideal.

- End points:

I do agree 6 and 12 month follow-ups are what we see in trials and literature, but we do not have time for that based on project timeline and in the guideline
it was suggested to avoid endpoints which can not fit into project timeline, that was a reason keeping only end-of treatment?

Vivian: for this two key points will be great to have a short call tomorrow in case your schedule allows, or just have you quick feedback via email.

We will try to share all components by Friday pm.

Many thanks to everyone!

Nestani Tukvadze Head of Research Unit National Center for Tuberculosis and Lung Diseases 50 Maruashvili str. 0101 Tbilisi, Georgia. Tel: (995 32) 2910769 Cell:
(995) 593733334

On Thursday, August 29, 2019, 11:53:45 AM GMT+4, Vivian Cox <[email-masked]> wrote:

Hello all,

Please find my edits/comments merged in with those of Nelly and Tamar’s excellent inputs.  I think Tamar raises a critical point that we need to clarify more
specifically why we are asking for additional funding to implement BPaL programmatically, especially if we are arguing that Georgia already has robust clinical, lab, and trial infrastructure.  This will likely become more clear as the budget is detailed, but
will need to be added to our executive summary and section 4.2 (activities).  I also added some descriptions of how we plan to observe and document our observations of the ‘programmatic challenges’ accompanying BPaL introduction into section 4.2 (underreported
objective #4), but please feel free to add to this if you can think of others.  This is one of the main arguments we are using to say our proposal is unique - we will test the use of BPaL and learn early lessons on how to use it programmatically - so we should
have an objective that describes how we are going to document this.

Under section 8.6, I think we could add that the high quality, ‘real world evidence’ or ‘real world data’ we collect on the patients that receive BPaL can be
submitted to WHO in future as a sizable cohort to contribute to future WHO recommendations on BPaL use.

I will review sections 5 and 8 and return comments on them later today.  Thanks, Vivian

On Aug 28, 2019, at 6:08 PM, Tamar Gabunia <[email-masked]> wrote:

Dear All,

Many thanks for keeping me in the loop of this communication
and giving a chance to review the draft. This is very clear and well written. I’ve added a few thoughts to Nelly’s file. My major advice would be to make the list of interventions under each objectives more clear. I expect the budget section will provide more
details on what the grant money is requested for and what would be NTP contribution.

Would be happy to have another look when finalized.

Special thanks to Vivien for all her great support.

With best regards.

პატივისცემით,

თამარ გაბუნია

მინისტრის მოადგილე

Sincerely,

Tamar Gabunia, MD,
MPH

Deputy Minister

From: Nelly
Solomonia [mailto:[email-masked]]

Sent: 28
August, 2019 20:22

To: Nestan
Tukvadze <[email-masked]>; Nino Lomtadze <[email-masked]>; Vivian
Cox <[email-masked]>; Vivian Cox <[email-masked]>; Maka Danelia <[email-masked]>;
Irma Khonelidze <[email-masked]>; Tamar Gabunia <[email-masked]>

Cc: Mari
Buziashvili <[email-masked]>; Zaza Avaliani <[email-masked]>;
Natalia Adamashvili <[email-masked]>; Nana Kiria <[email-masked]>

Subject: Re:
Fw: TB REACH V7 Application for your review and comments

Dear Colleagues,

Thank you very much for your hard work on the proposal. It's really was unbelievable to prepare such great draft in such limited time. Especial thanks to Vivian for her excellent
extra work.

Please, see some comments in attached file (pg. 5-9, comments NS 4-11). Hope, some of them will be helpful.

Sincerely,

Nelly

PS. Sure everybody knows, that my correct e-mail is: [email-masked]

On Tue, 27 Aug 2019 at 21:27, Nestan Tukvadze <[email-masked]> wrote:

ნელიკო შენგან წერილი დამიბრუნდა და ჯიმეილზე გიფორვარდებთ

Nestani Tukvadze Head of Research Unit National Center for Tuberculosis and Lung Diseases 50 Maruashvili str. 0101 Tbilisi, Georgia. Tel: (995 32) 2910769 Cell: (995) 593733334

----- Forwarded Message -----

From: Nestan
Tukvadze <[email-masked]>

To: Nino
Lomtadze <[email-masked]>; Neli Solomonia <[email-masked]>;
Vivian Cox <[email-masked]>; Vivian Cox <[email-masked]>; Maka Danelia <[email-masked]>;
Irma Khonelidze <[email-masked]>; Tamar Gabunia <[email-masked]>

Cc: Mari
Buziashvili <[email-masked]>; Zaza Avaliani <[email-masked]>;
Natalia Adamashvili <[email-masked]>; Nana Kiria <[email-masked]>

Sent: Tuesday,
August 27, 2019, 09:26:00 PM GMT+4

Subject: TB
REACH V7 Application for your review and comments

Dear Colleagues,

For time saving purposes I am sending this email to all of you for
your inputs and comments which needs to be provided by Thursday
pm latest, so
we can merge and respond on them by Friday and then proceed with submission hopefully on Saturday (as you know we got a little bit of extension till Sunday).

As for now the main parts of the application are completed, we have
removed OR component and incorporated this aspects as a project endpoints around programmatic implementation of BPaL.

Dear Tamar and Dear Irma,

In case your time allows will be great to have your feedback in written
or I am available for a call at any time if you deem necessary, since this morning I am back to Georgia.

Dear Maka:

As I was informed we are waiting from you completed section #6 on
budget, starting from 6.3.

Please, inform if this is not the case and will work on this as well,
but will definitely need from you or somebody from GF the cost sharing estimation with defined activities and corresponding budget lines.

Dear Vivian:

Hope you are safely back home and just checking if you got chance
to continue working on the proposal, please provide your version via email and will incorporate your parts in current draft or if easier then please provide feedback on this draft.

Dear Nino:

It is great you can contribute on 29th, there are few parts where
we indicated you name in track changes to save your time in case you can not read the full proposal. On those particular parts your contribution will be very important.

Many thanks to everyone and particularly to Natalia for drafting gender
related sections, which we have the less evidence around in TB and as I know she could not find much for HS access related studies also, so if anyone can contribute on this aspects will be wonderful.

Looking forward to everyone's feedback and please keep this email
communication chain for further correspondence.

With best,

Nestani

Nestani Tukvadze Head of Research Unit National Center for Tuberculosis
and Lung Diseases 50 Maruashvili str. 0101 Tbilisi, Georgia. Tel: (995 32) 2910769 Cell: (995) 593733334

--

Nelly Solomonia

National Center for Tuberculosis and Lung Diseases;

Tbilisi State Medical University.

Tel: +995 599 884409 or +995 551 258399

Email: [email-masked] , [email-masked],

Web: http://www.tbgeo.ge; http://www.tsmu.edu/

--

Nelly Solomonia

National Center for Tuberculosis and Lung Diseases;

Tbilisi State Medical University.

Tel: +995 599 884409 or +995 551 258399

Email:
[email-masked] , [email-masked],

Web:
http://www.tbgeo.ge;
http://www.tsmu.edu/