Using observational analysis of multiple sclerosis relapse to design outcomes-based contracts for disease-modifying drugs: a feasibility assessment

Abstract

Objective:

To assess predictors and costs of multiple sclerosis (MS) relapse, a potential outcome measure in payer-manufacturer risk-sharing agreements for disease-modifying drugs (DMDs).

Methods:

A retrospective cohort analysis of medical/pharmacy claims was used. Study patients had ≥1 DMD (interferon beta, glatiramer, natalizumab) claim, without DMD claims in a 6-month pre-period before DMD initiation; were aged 18–64 years and continuously enrolled from the pre-period through a 24-month post-period; and had ≥2 MS medical claims during the 30-month study period. Post-period relapse cohorts included: (1) severe (hospitalization with MS diagnosis); (2) moderate (outpatient services including intravenous methylprednisolone); and (3) none. Poisson regression modeled severe relapse frequency, logistic regression modeled ≥1 severe relapse, and generalized linear modeling predicted healthcare costs. Tested predictors included demographics, insurance type, index DMD, pre-period health status, and DMD medication possession ratio (MPR).

Results:

Severe relapse was experienced by 14.5% and moderate relapse by 13.8% of 2291 patients. In logistic regression, severe relapse was predicted by plan type; age (odds ratio [OR]?=?1.018, 95% confidence interval [CI]?=?1.005–1.031); pre-period Charlson Comorbidity Index (OR?=?1.307, 95% CI?=?1.166–1.464); pre-period proxy measure indicating impaired activities of daily living (OR?=?1.470, 95% CI?=?1.134–1.905); pre-period MS hospitalization (OR?=?2.174, 95% CI?=?1.537–3.074); and DMD non-adherence (MPR OR?=?0.101, 95% CI?=?0.068–0.151). Poisson regression results were similar. Predicted mean [standard deviation] all-cause healthcare expenditures were tripled for patients with severe compared with moderate relapse ($48,173 [$8665] and $13,334 [$1929], respectively).

Limitations:

Commercially insured patients from a single payer; use may have been inconsistent with approved indications; proxy relapse measure may have misclassified patients.

Conclusions:

Severe MS relapses requiring hospitalization, although affecting less than 15% of patients initiating DMD treatment, are associated with high medical costs. The only actionable predictor of severe relapse identified in observational analysis was MPR, raising questions about the feasibility of using observational data to guide outcomes-based contracting.     

东亚货币一体化的国际风险分担机制分析——基于第二代最优货币区理论的拓展

在经济全球化的背景下,区域货币一体化对于区域内各国的经济发展有着重要意义。当前的国际金融危机使东亚地区货币合作又重新进入人们的视野,关于东亚货币一体化的可行性分析也进入了一个崭新的阶段。此时,我们更需要从抵御风险,实现共同发展的角度来探讨东亚货币一体化。中国作为东亚区域内有影响力的大国,应对此问题有深入思考。本文对最优货币区理论进行了有益的拓展,建立了基于微观基础的国际风险分担机制模型,并运用动态优化的方法严格证明了货币一体化所形成的国际风险分担机制使成员方达到消费保险的目的,这为进一步推动东亚货币一体化的建设提供了新的理论依据。     

Banks, markets, and efficiency

A competitive financial system can help reduce banks’ monopoly power and the associated inefficiencies. However, according to Diamond (J Polit Econ 105: 928–956, 1997) and Fecht (J Eur Econ Assoc 6(2), 2004) competition with the financial sector may also constrain the amount of liquidity insurance that banks can provide to households affected by unobservable idiosyncratic liquidity shocks. To study this trade-off, we model competition between banks and between banks and financial markets. Our analysis shows that competition between banks and financial markets can constrain the risk-sharing offered by deposit contracts. This effect is the same if competition between banks mainly affects the reallocation of deposits. However, if banking competition primarily affects new deposits, then such competition only limits inefficient monopoly rents without restraining risk-sharing. We would like to thank Diemo Dietrich, Phil Dybvig, Hans Peter Grüner, Martin Hellwig, Elu von Thadden, Uwe Vollmer, Wolf Wagner as well as seminar participants at the Bundesbank, at the University of Mannheim, at the University of Tilburg, at the 3rd Workshop on Monetary and Financial Economics in Halle, at the University of Lausanne, at the First ProBanker Symposium in Maastricht, at the Global Finance Conference 2005 in Dublin, at the European Economic Association Meeting 2005 in Amsterdam, at the International Finance Conference 2005 in Copenhagen, and at the German Economic Association Meeting 2005 in Bonn. We thank Mike Demott for editorial assistance. The views expressed here are those of the authors and not necessarily those of the Deutsche Bundesbank, the Federal Reserve Bank of New York, or the Federal Reserve System.     

Does financial integration affect real exchange rate volatility and cross-country equity market returns correlation?

Existing empirical studies show that financial integration affects the behavior of average excess returns, cross-country equity market returns (EMR) correlations and real exchange rate (RER) volatility. We employ a recently developed two-country model with recursive preferences, frictionless and complete markets and highly correlated long-run innovations to examine whether full financial integration (i.e. full risk-sharing) affects the US-Canada EMR correlation and the US RER volatility, consistently with existing empirical findings. First, full risk-sharing gives rise to a relatively high RER volatility. Second, it induces very strong positive cross-country EMR correlations. Both quantities are higher than those observed in the US-Canada asset pricing data, and increase as the risk-sharing incentive increases. In contrast, “international consumption quantities” are weakly sensitive to changes in the level of aversion to consumption and utility risk.     

AGRARIAN LAND TENANCY IN PREWAR JAPAN: CONTRACT CHOICE AND IMPLICATIONS ON PRODUCTIVITY

We study the tenancy contract choice and its impact on productivity in the prewar Japanese agriculture, where a unique contractual form, the rent-reduction contract, was predominant. Theoretically, this contract is more efficient than share tenancy or fixed-rent contract in terms of provision of incentives and risk-sharing, and thus raises the question of why such an efficient contract was uncommon outside Japan. We argue that transaction costs on the execution of rent reduction were the key element in the adoption of this contract. In prewar Japan, local communities played some role in governing the process of rent reduction and mitigated such costs. Thus the study proposes transaction costs and institutions as additional determinant of tenancy contract choice. We also find that higher prevalence of tenancy was associated with lower average rice yield at the prefectural level and such correlation was stronger in prefectures with a greater proportion of share tenancy.     

Incomplete market participation, endogenous endowment risks and welfare

This paper investigates the equilibrium growth rate of capital stock and social welfare when risk-sharing externalities are incorporated into the infinite-horizon model where endowment risks are endogenized by the degree of incomplete market participation. There exist Nash equilibria depending on the degree of market participation. Under equilibrium with incomplete market participation, the endowment risks cannot be fully diversified as they induce precautionary savings and the over-accumulation of capital stocks while spillover effects on production technologies lead to the under-accumulation of capital stocks. This may have desirable effects on economic growth and improve social welfare.     

International asset markets and real exchange rate volatility

The real exchange rate is very volatile relative to major macroeconomic aggregates and its correlation with the ratio of domestic over foreign consumption is negative (Backus–Smith puzzle). These two observations constitute a puzzle to standard international macroeconomic theory. This paper develops a two country model with complete asset markets and limited enforcement for international financial contracts that provides a possible explanation of these two puzzles. The model performs better than a standard incomplete markets model with a single non-contingent bond unless very tight borrowing constraints are imposed in the latter. With limited enforcement for both domestic and international financial contracts, the model's asset pricing implications are brought into line with the empirical evidence, albeit at the expense of raising real exchange rate volatility.     

Two-persons efficient risk-sharing and equilibria for concave law-invariant utilities

Efficient risk-sharing rules and equilibria between two agents with utilities in a class that contains the rank dependent expected utility (RDU) are fully characterized. Specific attention is given to the RDU. Call-spreads and contracts with mixed regimes are shown to be efficient. Closed-form solutions are obtained for several examples.      

Modeling of the clinical and economic impact of a risk-sharing agreement supporting a treat-to-target strategy in the management of patients with rheumatoid arthritis in France

Objectives: To evaluate the cost-effectiveness of a Treat-to-Target strategy with certolizumab pegol in patients with rheumatoid arthritis in the context of a pay-for-performance agreement in which medication costs are refunded in case of discontinuation during the first 3 months of treatment.

Methods: The Treat-to-Target strategy consisted of a systematic switch to second-line tumor necrosis factor (TNF)α inhibitor in case of an unmet ACR50 response at 3 months compared to current routine clinical practice. A reference cohort treated first-line with certolizumab pegol according to current practice without systematic switching was considered as the comparator. A decision-tree model was constructed to estimate clinical outcome (health assessment questionnaire-disability index or HAQ-DI score), time spent in ACR50 response (ACR 50), and direct costs of treatment over a 2-year period. HAQ scores were derived from American College of Rheumatology 50 (ACR50) responses. All TNFα inhibitors were assumed to have equivalent efficacy and tolerability. Costs were estimated at 2013 French retail prices (date of the pay-for-performance agreement).

Results: The mean duration of an ACR50 response was 1.23 years in the Treat-to-Target strategy certolizumab pegol cohort vs 0.98 years in the reference cohort, resulting in a mean gain in HAQ at 24 months of 0.117. The Treat-to-Target strategy with a mix of TNFα inhibitors as second-line therapy was more expensive than the reference strategy in absolute terms, but this difference was entirely offset by the pay-for-performance agreement. The Treat-to-Target strategy was, thus, cost-neutral over a 2-year period after the payback of CZP cost for patients not achieving the target at 3 months.

Conclusions: In the context of a pay-for-performance agreement, the management of patients with rheumatoid arthritis using a Treat-to-Target strategy with certolizumab pegol in first line is dominant compared to standard use of this drug in the French setting in 2013.     

Robust bubbles with mild penalties for default

Limited enforcement of debt contracts and mild penalties for default can lead to low equilibrium interest rates, to ensure debt repayment. Low interest rates, in turn, create conditions for bubbles. I show that bubbles in unsecured private debt exist when the punishment for default is a permanent or a temporary interdiction to trade. Bubbles are an inefficient source of liquidity, as they lower interest rates and reduce welfare by discouraging saving.