TY - JOUR
T1 - Generating health technology assessment evidence for rare diseases
AU - Facey, Karen
AU - Granados, Alicia
AU - Guyatt, Gordon
AU - Kent, Alastair
AU - Shah, Nilay
AU - Van Der Wilt, Gert Jan
AU - Wong-Rieger, Durhane
N1 - Publisher Copyright:
© Cambridge University Press 2014.
PY - 2014/11/26
Y1 - 2014/11/26
N2 - Objectives: Rare diseases are often heterogeneous in their progression and response to treatment, with only a small population for study. This provides challenges for evidence generation to support HTA, so novel research methods are required. Methods: Discussion with an expert panel was augmented with references and case studies to explore robust approaches for HTA evidence generation for rare disease treatments. Results: Traditional RCTs can be modified using sequential, three-stage or adaptive designs to gain more power from a small patient population or to focus trial design. However, such designs need to maintain important design aspects such as randomization and blinding and be analyzed to take account of the multiple analyses performed. N-of-1 trials use within-patient randomization to test repeat periods of treatment and control until a response is clear. Such trials could be particularly valuable for rare diseases and when prospectively planned across several patients and analyzed using Bayesian techniques, a population effect can be estimated that might be of value to HTA. When the optimal outcome is unclear in a rare disease, disease specific patient reported outcomes can elucidate impacts on patients' functioning and wellbeing. Likewise, qualitative research can be used to elicit patients' perspectives, with just a small number of patients. Conclusions: International consensus is needed on ways to improve evidence collection and assessment of technologies for rare diseases, which recognize the value of novel study designs and analyses in a setting where the outcomes and effects of importance are yet to be agreed.
AB - Objectives: Rare diseases are often heterogeneous in their progression and response to treatment, with only a small population for study. This provides challenges for evidence generation to support HTA, so novel research methods are required. Methods: Discussion with an expert panel was augmented with references and case studies to explore robust approaches for HTA evidence generation for rare disease treatments. Results: Traditional RCTs can be modified using sequential, three-stage or adaptive designs to gain more power from a small patient population or to focus trial design. However, such designs need to maintain important design aspects such as randomization and blinding and be analyzed to take account of the multiple analyses performed. N-of-1 trials use within-patient randomization to test repeat periods of treatment and control until a response is clear. Such trials could be particularly valuable for rare diseases and when prospectively planned across several patients and analyzed using Bayesian techniques, a population effect can be estimated that might be of value to HTA. When the optimal outcome is unclear in a rare disease, disease specific patient reported outcomes can elucidate impacts on patients' functioning and wellbeing. Likewise, qualitative research can be used to elicit patients' perspectives, with just a small number of patients. Conclusions: International consensus is needed on ways to improve evidence collection and assessment of technologies for rare diseases, which recognize the value of novel study designs and analyses in a setting where the outcomes and effects of importance are yet to be agreed.
KW - Patient outcome assessment
KW - Rare diseases
KW - Research design
KW - Technology assessment
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U2 - 10.1017/S0266462314000464
DO - 10.1017/S0266462314000464
M3 - Article
C2 - 25407328
AN - SCOPUS:84923593364
SN - 0266-4623
VL - 30
SP - 416
EP - 422
JO - International Journal of Technology Assessment in Health Care
JF - International Journal of Technology Assessment in Health Care
IS - 4
ER -