Marcia Reinhart, DPhil CMPP Principal, Tantalus Medical Communications

Health Technology Assessments

• Many definitions “Technology assessment in health care is a multidisciplinary field of policy analysis. It studies the medical, social, ethical, and economic implications of development, diffusion, and use of health technology.”

– International Association of HTA (INAHTA)

“A form of policy research that examines short- and long-term consequences of technology. . . safety, efficacy, patient-reported outcomes, real-world effectiveness, cost, and cost-effectiveness as well as social, legal, the application of a health care ethical, and political impacts.”

– International Society for Pharmacoeconomics and Outcomes Research (ISPOR)

Regardless of the technology assessed, HTAs include similar elements

HTA Clinical efficacy Safety Cost effectiveness

HTAs are used to support many health care decisions

Clinicians and patients • Prescribing decisions • Practice guidelines Public and private payers • Drug plan formularies • Level of coverage Hospitals • Technology acquisition • Hospital formularies

What is 'Market Access'?

• Governments/private insurers determine the

price

and

availability

of drugs via formulary designation Figure: Eichler GH

et al. Nat Rev Drug Discov

2010;9:277-91.

Market Access around the world

• Just as health care systems vary worldwide, the payer assessment process differs from country to country

Who conducts and uses HTAs?

• National/regional government-based agencies • Independent academic or consulting groups

How do HTAs fit into the decision making process?

• HTAs as part of the market access continuum Manufacturer submission • Conducts literature review, economic analysis, etc.

• Submits HTA-like document based on agency template report HTA agency Payer • Assesses manufacturer submission • May conduct independent review or rely on HTAs from 3rd parties • Submits recommendation to payer  • Makes final decision on reimbursement and availability of drug or device Payer often agrees with   HTA agency, although may be influenced by additional factors

Systematic review – an essential step of the HTA process

• Cochrane Collaboration definition: “… attempts to identify, appraise and synthesize all the empirical evidence that

meets pre specified eligibility criteria to answer a given research question

. Researchers conducting systematic reviews use explicit methods aimed at

minimizing bias

, in order to produce more reliable findings that can be used to

inform decision making

.”

Systematic review: process

1.

2.

3.

4.

Define research question      Develop study inclusion/exclusion criteria

P

atients

I

ntervention(s)

C

omparator(s)

O

utcomes

S

tudy type

PICOS

  Develop literature search strategy Typically conducted across multiple databases Search strategies should be

broad

enough to capture all relevant publications, but

narrow

enough to avoid excessive irrelevant information Screen studies for inclusion and collect relevant data

Example – acupuncture for the treatment of fibromyalgia

1.

Define research question

Example – acupuncture for the treatment of fibromyalgia

1.

2.

Define research question  Develop study inclusion/exclusion criteria

P

atients Diagnostic criteria?

Age?

Disease severity?

Comorbidities?

Ethnicity?

Example – acupuncture for the treatment of fibromyalgia

1.

2.

Define research question   Develop study inclusion/exclusion criteria

P

atients

I

ntervention(s) Frequency?

Definition of acupuncture?

Adjunct therapies?

Example – acupuncture for the treatment of fibromyalgia

1.

2.

Define research question    Develop study inclusion/exclusion criteria

P

atients

I

ntervention Placebo?

C

omparator(s) No treatment?

Drugs?

Other TCM techniques?

Physical therapy?

Example – acupuncture for the treatment of fibromyalgia

1.

2.

Define research question     Develop study inclusion/exclusion criteria

P

atients

I

ntervention(s) Pain reduction?

C

omparator(s)

O

utcomes Quality of life?

Physical function?

Adverse events?

Days off work?

Fatigue?

Example – acupuncture for the treatment of fibromyalgia

1.

2.

Define research question      Develop study inclusion/exclusion criteria

P

atients

I

ntervention(s) RCTs?

C

omparator(s)

O

utcomes

S

tudy type Non-RCTs?

Real-world evidence?

Economic evaluations?

Quasi randomized?

Example – acupuncture for the treatment of fibromyalgia

3.

Develop literature search strategy  Use both indexing terms (e.g. MeSH) and plain text terms  Draft searches to identify studies in categories (e.g. disease terms, intervention terms), combined at end Disease terms

Example – acupuncture for the treatment of fibromyalgia

3.

Combined Develop literature search strategy Therapy terms

Example – acupuncture for the treatment of fibromyalgia

3.

Develop literature search strategy Medline Cochrane Embase congress abstracts Other sources?

ALL COMBINED (duplicates removed)

Example – acupuncture for the treatment of fibromyalgia

4.

Screen studies for inclusion

Data extraction and synthesis: The meta-analysis

• Multiple studies are combined statistically to reveal the overall effect of an intervention  A summary (pooled) effect estimate is calculated as a

weighted average

of the effects estimated in the individual studies Individual studies • Box represents estimated effect • Lines represent 95% CI • Size of box represents weighting Summary intervention effect

Example – acupuncture for the treatment of fibromyalgia

• Meta-analysis for mean difference in pain

Risk of bias

• • A bias is a systematic error, or deviation from the truth, in results or inferences  Selection, performance, detection, attrition, reporting Several tools have been developed to assess bias

Role of medical writers in HTAs

•

NICE single technology appraisal (STA)

Section A – Decision problem

1.

2.

Description of technology under assessment Context 3.

4.

5.

 Equality Innovation Statement of decision problem May include >1 research question

Role of medical writers in HTAs

•

NICE single technology appraisal (STA)

Section B – Clinical and cost effectiveness

6.

Clinical evidence 7.

Cost effectiveness

Section C – Implementation

8.

9.

10.

11.

Assessment of factors relevant to NHS/other parties References Appendices Related procedures for evidence submission • Systematic review • Meta-analysis • Non-RCT evidence • Safety data • Systematic review for published analyses • Report and interpret results of own economic model(s)

Example – new class of drug to treat rheumatoid arthritis

Section B – Clinical and cost effectiveness

6.

Clinical evidence

Example – new class of drug to treat rheumatoid arthritis

Section B – Clinical and cost effectiveness

6.

Clinical evidence Results from the systematic review:  Phase III clinical trial of new drug (B) vs placebo (A)     Phase II clinical trial of new drug (B) vs placebo (A) 3 RCTs of competitor (C) vs placebo (A) 2 RCTs of competitor (C) vs other competitor (D) 3 single-arm non-RCTs How do we use this information to compare the new drug (B) to competitors C and D??

Network meta-analyses/indirect treatment comparison

• Network meta-analysis can be used to infer the comparative effectiveness of treatments of interest that have

not been directly compared in trials

Example – new class of drug to treat rheumatoid arthritis

Section B – Clinical and cost effectiveness

6.

Clinical evidence Safety data  AEs from RCTs and non-RCTs   Post-marketing surveillance data (if available) Other sources of real-world evidence

Example – new class of drug to treat rheumatoid arthritis

Section B – Clinical and cost effectiveness

6.

Clinical evidence 7.

Cost effectiveness

The cost-effectiveness plane

• A new treatment can be compared with an existing therapy based on its effect on

cost

and

effect differences

Cost difference (+)

Dominated Trade-off

Effect difference ( −)

Trade-off SC Dominant

Effect difference (+) Cost difference (−) SC = standard care

Key concept: QALYs

• In

cost-utility

analyses, effectiveness is measured in quality-adjusted life years (QALYs)  QALYs incorporate

gained both quality and quantity of life

from an intervention QoL Improvement of

quality

of life with new treatment Improvement of

quantity

of life with new treatment • Estimated using

utility values

QALYs

without

new treatment (standard care) Time Figure: adapted from McCabe C. Hayward Group Ltd. 2009

Key concept: ICER

• Incremental cost-effectiveness ratio  “costs per outcome” (cost-

effectiveness

“costs per QALY” (cost-

utility

analysis) analysis) or Costs Treatment – Costs Standard care QALYs Treatment – QALYs Standard care = ICER

Key concept: ICER

Costs Treatment – Costs Standard care QALYs Treatment – QALYs Standard care

Treatment Standard Care Total costs

$20,000 $10,000 = ICER

Life-years gained (LYG)

7 5

Utility for LYG

0.5

0.6

Incremental cost, Treatment vs Std. Care

$10,000

Incremental life-years

2

Incremental cost/LYG

$5000/year

Incremental QALYs

0.5

QALYs

3.5

3.0

ICER cost/QALY

$20,000/ QALY

Economic analysis: “willingness to pay” threshold

• Some countries/health care systems use an official or unofficial threshold of acceptable ICERs for new technology assessments Cost difference (+)

WTP threshold Reject

Effect difference ( −)

SC Accept

Effect difference (+) Cost difference (−)

Example – new class of drug to treat rheumatoid arthritis

• • An economic model determines that the ICER for the new drug is $40,000/QALY If the WTP was $50,000/QALY, this drug would fall into the range of acceptable cost/QALY Cost difference (+)

WTP threshold Reject X

Effect difference ( −)

SC Accept

Effect difference (+) Cost difference (−)

Cost-utility: sensitivity analysis

• Calculating costs per QALY requires estimation of several parameters  utility values   cost of treatment duration of treatment/patient lifespan (“time horizon”) • •

Base case

=

best estimate

of all parameters Sensitivity analyses test alternative parameter estimates to assess the range of possible results

One-way sensitivity analysis

• Each parameter varied one-at-a-time over plausible range

base case

Tornado diagram ICER ($thousand/QALY) Figure: Reynolds MR

et al. Circ-Arrhythmia Elec

2009;2:362 –69.

Example – new class of drug to treat rheumatoid arthritis

• Sensitivity analysis shows that the new drug may rise above the WTP threshold in certain circumstances Effect difference ( −) Cost difference (+)

Reject X X X X X X X WTP threshold SC Accept

Effect difference (+) Cost difference (−)

Other sensitivity analyses used in HTA

• • Scenario analysis   Similar to a one-way sensitivity analysis, however, assessments are made by varying multiple parameters at the same time Example = best-case and worst-case analyses Probabilistic sensitivity analysis  “Drug X has a 86% probability of falling within the WTP threshold of $50,000/QALY”  More statistically complex; assesses distributions of data for multiple inputs over the course of multiple simulations

Cost-utility is not the only economic analysis used in HTAs Cost-consequences analysis Cost-minimization analysis Cost-effectiveness analysis Cost-utility analysis Cost-benefit analysis Budget impact analysis

Estimates cost and value of interventions, but leaves it to the reader to draw conclusions Compares input costs, but assumes outcomes are equivalent (e.g., bioequivalent drug comparisons) Measures costs in dollars and reports outcomes in natural health units (e.g., mmHg reduction) or ratios (differences in cost/difference in outcomes) Measures outcomes based on years of life and quality of life obtained with treatment Enumerates and compares costs and benefits achieved in monetary terms Estimates effect of intervention on overall cost to organization or health plan

Desirable qualities in HTA medical writers

• • • • • • Well-versed in literature searching  Experience with multiple databases and multiple interfaces (e.g. PubMed vs Ovid) Attention to detail – screening and data extraction Understanding of evidence grading systems Knowledge of statistical methods (e.g. meta analysis, NMA, sensitivity analyses) Understanding of health economic models Excellent writing skills