Addressing the research methodology challenges in rare cancers

The world of rare cancers is a strange one. For patients there is no such thing as rarity – ‘I’ve got this disease and that’s not rare is it?’ For doctors there are specific challenges, mostly around the absence of evidence which gives some certainty to their recommendations and decisions. This is what makes research so important in rare diseases.

At the same time research is difficult. Getting adequate numbers of patients to include in a study which can deliver a level of significance which points to certainty is a challenge. You either need to take a long time over the study or you need to widen the catchment to attract as many patients as you can from as many treatment centres as you can. Both of these issues carry costs, create challenges in consistency of observance of protocols, and maintaining the quality of the data gathered becomes complicated.

It is therefore encouraging to see the article in the latest edition of the European Journal of Cancer addressing the subject. It looks at the practical challenges of trial design in rare cancers from the experience of the International Rare Cancers Initiative. This is a project involving NCI (USA), EORTC (Europe) and Cancer Research UK (with the NIHR Cancer CRN) to develop key studies in very rare diseases.

The lead authors are Jan Bogaerts and Matt Sydes. Jan is the EORTC’s senior methodologist and Matt has a similar role with the MRC’s Clinical Trials Unit. The long list of authors includes the PIs on the various studies and other key trial designers, with Prof Matt Seymour from NCRI/NCRN as final author.

As a description of the decision-making in trial design for rarer cancers it is a masterpiece. The problems and the solutions tested to address them are described in detail (enough for a statisticiain in most cases). This is a recommended read for anyone involved in clinical trial development. It is a free download.

Three of the eight trials developed so far are in sarcomas – two uterine and one for Ewings sarcoma. There are other trials in development and these include one for Desmoplastic Small Round Cell Tumour (DSRCT), a sarcoma of late teenage years. DSRCT affects perhaps 15 patients each year in the UK and there are no treatments with proven efficacy for those who relapse after surgery.

While considering the challenges of research in rarer cancers a superb analysis of the issues was recently published in Annals of Oncology. This too is well worth the read. The principle authors include Dr Paolo Casali and Prof Jean-Yves Blay. The consensus group working with them on the paper includes a wide range of professionals and patient group representatives.