One challenge for HTA is that clinical trials conducted during medicine development may use outcomes and endpoints that HTA bodies or decision-makers do not consider relevant. Regulatory assessment and HTA assessment focus on different types of outcomes:

For example, regulatory approval, pharmaceutical companies must:

  • Provide evidence of beneficial health effects from randomised controlled trials against placebo or another comparator
  • Include this evidence in the submission dossier
  • Select an accepted comparator, often in consultation with regulatory authorities

🎯 Efficacy refers to the benefit of using a technology, programme or intervention to treat a particular problem under ideal conditions, such as during research in a laboratory or when following a rigorous protocol for a randomised clinical trial. According to EMA, this is the measurement of a medicine’s desired effect under ideal conditions, such as in a clinical trial.

🏥 Effectiveness refers to the benefit of using a technology, programme or intervention to address specific problem under general or routine conditions, rather than under controlled conditions, for example, by a physician in a hospital or by a patient at home.

🔍 Treatment effect refers to the effect on a person’s health status or well-being that is directly due to a treatment or intervention. It is usually estimated by investigators as the difference in outcome between the experimental and control groups.

HTA bodies may evaluate whether a newly approved medicine:

  • Shows positive outcomes in clinical settings
  • Provides additional value compared to existing therapies (not necessarily only pharmaceutical)
  • Justifies a possibly higher cost to the health system

Differences between Regulatory Approval, HTA, and Patients

  Regulatory approval HTA Patient
Decision(s) to be made by the stakeholder • Does the technology do more good than harm for patients with the defined target indication?
• Should this technology be marketed?		 • Does the technology offer useful, appropriate benefits for all or a select sub-group of patients in this healthcare system compared to what is most commonly used in the disease area?
• Are the costs associated with the technology affordable and justified by its benefits?		 • Is it effective?
• What benefit and/or harm should I expect from taking it?
• How does it compare to other treatments available?
• How much will it cost me?
• How convenient is the treatment?
Type of evidence required • Safety.
• Efficacy.
• Quality.		 • Safety.
• Effectiveness.
• Economics and budgetary impact.
• Social, ethical, legal, organisational impact.		 • Safety.
• Effectiveness.
Evidence considered • (Pre-launch) Randomised controlled trials, with a standard-of-care or placebo comparator.
• (Post-launch) Safety/pharmacovigilance (always), relative efficacy or effectiveness, when assessing a product’s benefit-risk profile in extended/long-term use.		 • Randomised controlled trials, observational studies.
• Systematic reviews of pertinent literature.
• Relative effectiveness and costs, as assembled from trials or through analytic techniques such as meta-analysis, modelling.		 • Personal and others’ experience.
• Results from trials explained in lay language.
Validity • Internal validity (can a causal conclusion be drawn without systematic bias?). • External validity (can the results of a study be generalised to other situations and to other people?). • Internal and external validity.
Outcomes • Hard clinical endpoint outcomes.
• Laboratory findings.
• Surrogate outcomes.
• Patient-relevant outcomes (increasingly).		 • Quality of life.
• Long-term clinical outcomes.
• Patient-relevant outcomes.		 • Outcomes relevant to me.
Comparator • Standard-of-care medicinal product (active control), or Placebo. • Active control, ideally reflecting what might be replaced by the new technology. • The best option available, or
• What I am currently taking if switching to new medicine.
• No treatment.
Time horizon • Trial duration.
• Post marketing studies.
• Pharmacovigilance over the lifetime of a product.		 • Life time; or at least the time needed to capture risks and benefits of treatment. • Time horizon relevant to me.

Table 1:  Adapted from: 1. Tsoi B, Masucci L, Campbell K, Drummond M, O’Reilly D, Goeree R. Harmonization of reimbursement and regulatory approval processes: a systematic review of international experiences. Expert Rev Pharmacoecon Outcomes Res. 2013 Aug;13(4):497–511. 2. Henshall C, Mardhani-Bayne L, Frønsdal KB, Klemp M. Interactions between health technology assessment, coverage, and regulatory processes: emerging issues, goals, and opportunities. Int J Technol Assess Health Care. 2011 Jul;27(3): 253–60.