Exploring variation in prescribing practices in rare diseases: the case of prescribing tolvaptan for autosomal dominant polycystic kidney disease

Background
Rare diseases pose a challenge to healthcare systems. Autosomal dominant polycystic kidney disease (ADPKD) is a rare kidney disease that has a single disease-modifying therapy, tolvaptan. However, its use varies between UK kidney centres. Little is known about how clinicians make prescribing decisions in ADPKD. This study examined variation in tolvaptan prescribing and factors influencing decision-making across UK kidney centres.

Methods
This mixed-methods study had four phases. An overview of 26 systematic reviews was conducted to adapt a conceptual model of prescribing decision-making to chronic conditions. ADPKD registry data was used to identify variation in tolvaptan prescribing across UK kidney centres. A multiple case study of three kidney centres was conducted with 12 interviews, 23 observations and 8 documents to explore reasons for this variation; the conceptual model was then refined for rare diseases. The final phase was a national survey to measure the extent to which these factors varied between centres.

Results
The overview identified factors relevant to prescribing decision-making in chronic conditions. Registry data showed variation in tolvaptan prescribing between kidney centres, mainly in initiation among eligible patients. The multiple case study suggested that variation arose from multiple interacting factors. Service configuration appeared to shape patient identification, eligibility assessment and initiation. Dedicated tolvaptan clinics improved coordination of prescribing. Although national guidelines define eligibility, centres varied in which criteria were used and how they were applied. Clinical leadership shaped prescribing norms. Pharmacist involvement appeared to increase guideline-adherence. How risks were communicated to patients varied and appeared to influence patient uptake. Survey data demonstrated variation across centres in all these factors.

Conclusions
Variation in tolvaptan prescribing for ADPKD between UK kidney centres appears to be influenced by differences in service configuration, clinical leadership, and local interpretation of eligibility criteria. This suggests that both system and clinician-level factors may shape prescribing decision-making in rare diseases and contribute to unwarranted variation in practice.