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Study coming out of Oxford summer course: Predicting hip fractures amongst patients initiating bisphosphonates

@Rijnbeek, @anthonysena and I had a great opportunity to take part in @Daniel_Prieto’s Oxford Summer School course on Real-World Data Epidemiology this week. As part of our segment of the training, the class identified a series of important clinical problems that could be informed through patient-level prediction, and chose one specific question to design and implement as a group.

The team settled on the following prediction problem:

Amongst patients initiating bisphosphonates after diagnosis of osteoporosis and after 40 years of age, which patients will have a hip fracture event within the 2 years following diagnosis?

We used ATLAS to define our target and outcome cohorts, then designed an analysis script using the PatientLevelPrediction package to learn models against any OMOP CDM-compliant database. We then used one of the newest features @jennareps created to externally validate the model on other data.

The preliminary results, generated during the course, were extremely promising. We trained a LASSO regression against a large US claims database, which yielded a XX-variable model that achieved a AUC=0.82 on the hold-out test set. The model was then externally validated against 5 different databases from UK, Japan, Germany, and other US claims/EHR data all achieve AUC>0.70 when directly applying the original model.

Based on the encouraging feasibility work, @Daniel_Prieto, @Rijnbeek and I intend to work with the students in the class to take this research forward to a full publication. We want to make this an OHDSI network study to allow others to participate in the fun! We will post a protocol and study package in the near future, and invite all of you to externally validate our model and participate in the publication. If folks want to participate or have thoughts about this work, please join this discussion thread!

Thanks @Daniel_Prieto for a wonderful week in Oxford. Great job and thank you for your contributions to the OHDSI community!

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Thanks @Patrick_Ryan , @Rijnbeek and @antonysena for a wonderful week and by kicking this collaborative project off.

I look forward to hearing more from others in the community who will you contribute/validate this tool in their data. I can reassure you this is of clinical relevance, and that I will make sure we get this published sooner than later

Cheers
dani

I am excited to provide technological guidance on the regularized regression used in the prediction. Underlying it all was PLP and the Cyclops package for very large-scale regressions.

best, Marc

I look forward to helping to validate the prediction model. Count Columbia in!

Very nice project and let’s open shared document somewhere where we can start gathering everyone’s input; we have already a self-generated draft as a working document.
Can the draft of the publication be opened on Google Docs? --Just a starting point

@Daniel_Prieto: I am the guy who volunteered in the summer school :slight_smile:

Best regards
Marc Twagirumukiza
Ghent University -Belgium & Janssen (team of Bart)

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Great Job!! @Patrick_Ryan

I would like to take part in this project with my knowledge and database :smile: . I think that interpretation of the outcome would be important.

Yeesuk.

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Here’s a google doc with the start of a protocol, with initial listing of the target and outcome cohorts we created in class, the candidate predictors we selected, and the some of the model outputs we can expect to want to report on.

As a group, we should finalize our protocol so that we are all aligned and pre-specified on what prediction task we are achieving. Those interested in participating should add their name and affiliation(s) in the draft protocol, as well as author text and provide comments throughout. This protocol can serve to support any governance/approval processes that data sources may require before they can execute the study and share results.

Then, once we are aligned on the final protocol, we can design a final R study package which will execute the final analysis, which will likely amount to learning a model and internally validating it on one source, and externally validating on other databases.

At that point, we can being to prepare a manuscript of our findings.

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Nice to e-meet you @estone96 !
Look forward to your contribution/s to the protocol as shared by @Patrick_Ryan , and to your findings from S Korean data! I can see you might potentially -as myself- even be interested in using/testing the model in your clinic!

cheers
dani

awesome @twamarc !
I suggest we give a few days for other OHDSI cols contributions to the protocol and we can then beef it up for any necessary approvals including ISAC if we want to validate this in UK CPRD data

cheers
dani

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Hi All, Great project! @Patrick_Ryan @Rijnbeek @Daniel_Prieto @anthonysena I would like to participate and externally validate the model on the VA (Veteran’s Affairs) dataset, contingent upon approval from admin / IRB. Thanks, looking forward to contributing!

that would be awesome @igor_gorbenko ! let us make sure that the protocol we’re drafting serves the purpose for your IRB approvals. Is there a template we should look at for admin/IRB submission for VA?

bw

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Hi All,

@Rijnbeek mentioned this to me. I am definitely interested in contributing to this using the IPCI (Netherlands gp) database.

cheers,
Ross

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excellent news! I look forward to working with you @RossW

bw

I’m not sure there’s any rule written in stone, but I would not dwell much longer. @twamarc should we populate the protocol together? Email me and let’s get the ball rolling!

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Hi @Daniel_Prieto ,
sure, I was waiting to have a max of interested people in the community— I think we can start populate the protocol.
I inbox you to see the way forward.
Thanks
Marc

Hi @Daniel_Prieto, @twamarc @rijnbeek,@Patrick_Ryan,@anthonysena, and others.
If we have the right data, U of Colorado would like to participate!
Lisa

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t