Finally a complete revision of PE guideline after 8 years?

HIRA unveils cosigned research report on revising PE analysis

Study proposes detailed revision in analysis period, data source, utility and more

After long eight years, the Korean health authority seems to finally accept the pharmaceutical industry’s demand to amend the pharmacoeconomic analysis guideline.

 

Health Insurance Review and Assessment Service (HIRA) recently unveiled a final report on the cosigned research regarding ‘Pharmacoeconomic (PE) Analysis Guideline Revision Plan (Principal investigator: Professor Lee Tae-jin of Seoul National University Health Science Department and Professor Bae Eun Young of Gyeongsang National University College of Pharmacy).’ Aiming for a ‘complete revision’ of the PE analysis, HIRA has started the research from last year.

 

The research report, disclosed on Jan.

 

22, found countries the Korean PE analysis guideline refers to, such as the U.K., Australia and Canada, have entirely amended their guidelines after 2011.

 

And it claimed the Korean PE analysis guideline should also reflect the developed PE analysis methodology and precedents that the other countries have based since 2011.

 

The research team conducted a survey on stakeholders like pharmaceutical industry organization, patient and civic group, and related scholars, from July to September last year.

 

The team convened consultative meeting with Korean Research-based Pharmaceutical Industry Association (KRPIA), Korea Pharmaceutical and Bio-pharma Manufacturers Association (KPBMA), Korea Biomedicine Industry Association (KoBIA), Korea National Council of Consumer Organization, National Council of the Green Consumers Network, Korea Consumer Agency, National Health Insurance Policyholder Forum, Korean Association of Health Technology Assessment (KAHTA) and other experts.

 

The survey helped the research team to limit the scope of guideline revision down to perspective of revision, analysis period, analysis subject and population group, analytic techniques, comparison subject selection, data source (indirect comparison), items of cost, utility (health related quality of life), discount rate, model construction, and uncertainty.

 

The team recommended the guideline to remove ‘financial impact’ article, but to add ‘statistical consideration (estimated long-term effect, treatment switching (cross over) and etc.)’ and ‘analysis guideline for laboratory test drug.’ ◆ Cost: As the article of cost in PE analysis depends on the perspective, the researchers recommended using healthcare perspective instead of the existing limited societal perspective, as well as only including direct medical expense and excluding non-medical expense (transportation cost, time cost, nursing guardian cost and etc.) for the basic analysis.

 

In the PE analysis material submitted to this date, expert’s opinion takes up the majority of data source with seven cases (14 percent) in diagnostic cost and five cases (ten percent) in treatment cost.

 

Compared to data-focused referential material, expert opinion or cost and resource use quoted from hospital investigation have limited credibility or consistency.

 

Therefore, referencing expert opinion should require official statement of an academic society, or stipulated minimum number of expert panel to improve credibility and consistency.

 

Although the existing guideline does not mention drug wastage, the researchers suggested stating the cost of wastage volume, because it generates noticeable amount of expense.

 

◆ Utility, the healthcare related quality of life: Rounding up the recommendations made by HIRA, pharmaceutical companies, and civic groups, the researchers said following articles in the guideline about ‘utility’ should be revised; prioritization of utility measuring techniques; Health-related quality of life (HRQL) indicating tool and reviewing tariff selection; detailed guideline on mapping; detailed guideline of direct measuring; and additional review on minimal clinically important difference of utility.

 

Recommending the revised guideline to clarify preference of indirect measurement based on the Health Technology Assessment (HTA) of many other countries, the researchers also suggested using health state vignette-based direct measuring, calculating weighted value of quality of life via mapping, or quoting a value proposed in a published literature, as an option when lacking or having limited data quoted from preference-based measuring tool.

 

About reviewing and selecting HRQL tool and tariff, they argued the health authority should select a single set of tool and tariff to ensure consistency in policy-making process.

 

‘Tariff’ means the value that converts utility value in foreign country to fit the Korean landscape.

 

The primary recommendation is to select EQ-5D-3L, a tool used the most home and abroad so far, as a single tool and to select tariff developed in the most recent study ‘Lee et al.

 

(2009)’ with the largest sample as a standard tariff.

 

However, the team also proposed keeping the existing guideline as a secondary option, because a proper comparison study or qualitative evaluation on HRQL tool and tariff in Korea has not been conducted, yet, and related empirical data are insufficient.

 

◆ Discount rate: According to 50 cases of PE analysis material submitted to HIRA, 45 cases (90 percent) have been discounted and five cases (10 percent) have not been discounted.

 

The analysis period of the five cases was apparently under a year.

 

The researchers stated the discount rate for PE analysis should be reduced as well, because the social discount rate continues to descend due to changes in socio-economic conditions.

 

Hence, the report suggested the revised guideline should set 4.5 percent as an adequate level of discount rate, equivalent to the discount rate applied on preliminary feasibility assessment.

 

About applying the same discount rate on the cost and result, the report tried to persuade applying the unchanged rate, but applying either zero percent for no discount or three percent discount rate to analyze sensitivity.

 

Applying the discount rate of 4.5 percent for the entire period of basic analysis was suggested in case the period of PE analysis for the healthcare sector is longer than three decades.

 

But also as a sensitivity analysis, 3.5 percent could be applied after 30 years in case the applicant drug is essential for pediatric treatment.

 

◆ Perspective: Taking in account the state and realistic environment of reimbursement decision making, the researchers argued the analytic perspective should be amended.

 

Keeping in mind the interest of reimbursement listing reviewer is on the impact on the healthcare sector, the research team first recommended shifting the perspective from limited societal perspective to healthcare perspective and excluding items applicable for direct medical cost from the basic analysis.

 

So the cost should cover items centering the direct medical expense, but it should include nursing if the cost is reimbursed from long-term nursing insurance, whereas the effect should reflect benefit of health on the patient.

 

The secondary proposal suggested was maintaining the current guideline.

 

◆ Analysis period: The current guideline recommends the analysis to be conducted long enough to confirm major clinical endpoints.

 

The research team studied deliberation cases of similar diseases and contemplated on patient age (cohort joining age), expected life expectancy of general population group, patient’s survival rate, analysis period of similar drugs, clinical trial outcome (median OS), monitoring period, clinical consulting, and uncertainty for calculating analysis period.

 

The team advised to maintain the principal approach of the existing guideline, but to consider validity of calculated analysis period.

 

Also the team elaborated the revision, when comparing with other countries’ guidelines, should take in account the age of applicable population, life expectancy, survival rate based on epidemiological data, median OS observed from clinical trial, difference in survival rate between cohorts, monitoring period, numerous uncertainties inserted in model, similar drug evaluation case or cases in referential countries and expert consulting.

 

◆ Analytic techniques: The current guideline recommends using cost-utility analysis when quality of life is a crucial aspect or the health outcome is demonstrated in various indicators.

 

But the research team claims the guideline should provide more specific standard or analytic techniques to distinguish equivalence of effect.

 

They first advised offering more detailed guideline on selecting subject for cost-minimization analysis, expense item and submission data to be considered when conducting the cost-minimization analysis.

 

Regarding subject for cost-minimization analysis, the researchers recommended clarifying the cases of the drug effect is non-inferior (or superior) and recognizing the non-inferiority of the applicant drug in safety profile.

 

As for the cost estimation, the guideline should set equi-effective doses and provide cost of comparing options’, as well as other costs estimated from monitoring, adverse reaction relief, and others.

 

The secondary recommendation is to exclude cost-minimization analysis from the analytic techniques.

 

The researchers explained it would theoretically eliminate the issues of effect equivalence and uncertainty.

 

◆ Subject of comparison: The existing guideline stipulates selecting alternative treatment option with the highest market share as a reference.

 

When there are multiple drugs with similar market share, multiple options can be selected for comparison, and other therapy and surgery can be used as reference if there is no other alternative option.

 

The referential option selection has been an issue raised by the pharmaceutical industry for a long while.

 

The Korean guideline clearly states to select a substitutable option with the highest market share, but many of other countries’ guideline does not specify “the highest market share.” As a primary recommendation, the researchers suggested keeping the basic principal of selecting the ‘most used’ drug for comparison, but to loosen the description of ‘highest market share’ to prioritize replaceability when selecting a referential treatment option.

 

The majority of the researchers were negative about providing a range of options like in Australia or limiting the option to reimbursed treatment, but they agreed on having government committee to discuss or negotiate with pharmaceutical companies based on submitted PE analysis material and market status.

 

However, the team put down a precondition that comparing with existing treatment option, which fails to treat health condition but has no other option, is ‘not automatically neglected from referential candidate list.’ ◆ Data source: The HIRA’s guideline barely mentions of indirect comparison, but a separate indirect comparison guideline is used to accommodate, and the government agency has already opened up about possibly accepting simple comparison of drugs as they reflected stakeholders’ demands, since the 2014 revision.

 

The researchers elaborated “It could be seen that it was actually more lenient than other countries’ guidelines,” and advised that the revised guideline should edit the detailed guideline and supplementary explanation in a wider sense.