What does it take to make progress in a disease?

In this paper, we investigate what conditions need to be in place to make progress in combating a disease using a case-control design: we compare cases (diseases with a successful therapy) to controls (diseases without a successful therapy). We find five conditions ('hurdles') must typically be cleared for success: (A) understanding of biological drivers, (B) ability to modulate biology, (C) availability of translational models, (D1) ability to identify patients, and (D2) ability to measure clinical response. This framework is similar to ones deployed to evaluate individual drug candidates but is employed here to make inferences about entire diseases. It can be used to identify diseases most ready for progress, where efforts should be focused to make progress in diseases that are currently intractable, and where the industry could benefit from development of tools to address the hurdle that is most commonly the last to be cleared across diseases-namely, (C) translational models. ### Competing Interest Statement MSR, JD, and US are employees of Boston Consulting Group (BCG), a management consultancy that works with the world's leading biopharmaceutical companies. MJD, MD, RAF, and SCH are previously employees of BCG. ### Funding Statement The research for this specific article was funded by BCG's Health Care practice. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Available data produced in the present work are contained in the manuscript.