The main aim of health technology assessment (HTA) is to inform decision making by health care policy makers. It is a systematic process that evaluates the use of health technologies and generally involves a critical review of international evidence related to clinical effectiveness of the health technology vs. the best standard of care. It can also include an evaluation of cost effectiveness, and social and ethical impacts in the local health care system. The HTA process advises whether or not a health technology should be used, and if so, how it is best used and which patients are most likely to benefit from it. The importance of patient involvement in HTA is becoming widely recognized, for scientific and democratic reasons. The extent of patient involvement in HTA varies considerably across Europe. Commonly HTA is still focused on quantitative evidence to determine clinical and/or cost effectiveness, but the interest in understanding patients' experiences and preferences is increasing. Some HTA bodies provide support for participation in their processes, but again this varies widely across Europe. The involvement of patients in HTA is determined at the national and regional level, and is not subject to any European-wide legislation. The guidance text presented in this article was developed as part of the work of the European Patients' Academy on Therapeutic Innovation (EUPATI) and covers the interaction between HTA bodies and patients and their representatives when medicines are being assessed. Other EUPATI guidance documents relate to patient involvement in pharmaceutical industry-led research and development, ethics committees, and regulatory authorities. The guidance provides recommendations for activities to support patient involvement in HTA bodies and specific guidance for individual HTA processes. It seeks to improve patient involvement, using the outcomes of published research and consensus-building exercises. It also draws on good practice examples from individual HTA bodies. The guidance is not intended to be prescriptive and should be used according to specific circumstances, national legislation, or the unique needs of each interaction. This article represents the formal publication of the HTA guidance text with discussion about recent progress in, and continuing barriers to, patient involvement in HTA.

Chronic subjective tinnitus is an auditory phantom phenomenon characterized by abnormal neuronal synchrony in the central auditory system. As shown computationally, acoustic coordinated reset (CR) neuromodulation causes a long-lasting desynchronization of pathological synchrony by downregulating abnormal synaptic connectivity. In a previous proof of concept study acoustic CR neuromodulation, employing stimulation tone patterns tailored to the dominant tinnitus frequency, was compared to noisy CR-like stimulation, a CR version significantly detuned by sparing the tinnitus-related pitch range and including substantial random variability of the tone spacing on the frequency axis. Both stimulation protocols caused an acute relief as measured with visual analogue scale scores for tinnitus loudness (VAS-L) and annoyance (VAS-A) in the stimulation-ON condition (i.e. 15 min after stimulation onset), but only acoustic CR neuromodulation had sustained long-lasting therapeutic effects after 12 weeks of treatment as assessed with VAS-L, VAS-A scores and a tinnitus questionnaire (TQ) in the stimulation-OFF condition (i.e. with patients being off stimulation for at least 2.5 h). To understand the source of the long-lasting therapeutic effects, we here study whether acoustic CR neuromodulation has different electrophysiological effects on oscillatory brain activity as compared to noisy CR-like stimulation under stimulation-ON conditions and immediately after cessation of stimulation. To this end, we used a single-blind, single application, cross over design in 18 patients with chronic tonal subjective tinnitus and administered three different 16-minute stimulation protocols: acoustic CR neuromodulation, noisy CR-like stimulation and low frequency range (LFR) stimulation, a CR type stimulation with deliberately detuned pitch and repetition rate of stimulation tones, as control stimulation. We measured VAS-L and VAS-A scores together with spontaneous EEG activity pre-, during- and post-stimulation. Under stimulation-ON conditions acoustic CR neuromodulation and noisy CR-like stimulation had similar effects: a reduction of VAS-L and VAS-A scores together with a decrease of auditory delta power and an increase of auditory alpha and gamma power, without significant differences. In contrast, LFR stimulation had significantly weaker EEG effects and no significant clinical effects under stimulation-ON conditions. The distinguishing feature between acoustic CR neuromodulation and noisy CR-like stimulation were the electrophysiological after-effects.Acoustic CR neuromodulation caused the longest significant reduction of delta and gamma and increase of alpha power in the auditory cortex region. Noisy CR-like stimulation had weaker and LFR stimulation hardly any electrophysiological after-effects. This qualitative difference further supports the assertion that long-term effects of acoustic CR neuromodulation on tinnitus are mediated by a specific disruption of synchronous neural activity. Furthermore, our results indicate that acute electr...

The importance and merits of greater patient involvement in medicines research and development (R&D) are commonly acknowledged and are thought to offer benefits for all involved parties. It helps to improve discovery, development, and evaluation of new effective medicines, based on the collaborative identification and understanding of unmet needs, research priorities, optimization of clinical study design, outcome measures, and endpoint development. It can result in increased transparency, trust and mutual respect between patients and other stakeholders. This applies to all stages of medicines R&D, from industry-led research, to regulation and licensing of medicines, to appraisal by health technology assessment (HTA) bodies. Integration of patients into the medicines development process needs to be structured and governed by clear rules and modes of operation to be effective and yield the best results for all stakeholders. Existing codes of practice for patient involvement with various stakeholders do not comprehensively cover the full scope of R&D, with the exception of more general statements applicable to interaction. Overarching guidance on meaningful and ethical interaction is missing. One specific aim of the European Patients' Academy on Therapeutic Innovation (EUPATI) was to close this gap through the development of guidance documents for selected stakeholders. Four separate guidance documents were developed, incorporating the results from comprehensive internal and external consultation. They cover patient involvement in: pharmaceutical industry-led medicines R&D; ethics committees; regulatory authorities; HTA. Each guidance suggests where patient involvement could be adopted or strengthened. The EUPATI guidance document for patient involvement in industry-led medicines research and development covers the interaction between patients and the pharmaceutical industry within all functions throughout the medicines R&D lifecycle in relation to medicines for human use. It relates to activities pre-approval and post approval, involving individuals and groups of patients. The guideline distinguishes between the level of expertise in a disease area that is required and the different areas where patient involvement can take place; however, this is not meant to limit involvement, and these opportunities may change and increase over time. This EUPATI guidance document is aimed at the pharmaceutical industry who want to engage patients in R&D activities, however all stakeholders involving patients in pharmaceutical-led medicines R&D should understand and use this EUPATI guidance document.

No abstract